Addex Therapeutics to Present at Access to Giving Virtual Conference on July 14, 2021

Geneva, Switzerland, July 7, 2021 - Addex Therapeutics (SIX:ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, announced today that Chief Executive Officer, Tim Dyer, will present at Access to Giving Virtual Conference at 9 AM ET on July 14, 2021. Mr. Dyer will give a corporate update, including an overview of recent advances in Addex’s clinical trial program. The conference is free to all registrants.

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Addex Therapeutics to Present at Access to Giving Virtual Conference on July 14, 2021

Beyond CAR-T: New Frontiers in Living Cell Therapies – UCSF News Services

Our cells have abilities that go far beyond the fastest, smartest computer. They generate mechanical forces to propel themselves around the body and sense their local surroundings through a myriad of channels, constantly recalibrating their actions.

The idea of using cells as medicine emerged with bone marrow transplants, and then CAR-T therapy for blood cancers. Now, scientists are beginning to engineer much more complex living therapeutics by tapping into the innate capabilities of living cells to treat a growing list of diseases.

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That includes solid tumors like cancers of the brain, breast, lung, or prostate, and also inflammatory diseases like diabetes, Crohns, and multiple sclerosis. One day, this work may extend to regenerating tissues outside or even inside the body.

Taking a page from computer engineers, biologists are trying their hands at programming cells by building DNA circuits to guide their protein-making machinery and behavior.

We need cells with GPS that never make mistakes in where they need to go, and with sensors that give them real-time information before they deliver their payload, said Hana El-Samad, PhD, a professor of biochemistry and biophysics. Maybe they kill a little bit and then deliver a therapeutic payload that cleans up. And the next program over encourages the rejuvenation of healthy cells.

These engineered cell therapies would be a huge leap from traditional therapies, like small molecules and biologics, which can only be controlled through dose, or combination, or by knowing the time it takes for the body to get rid of it.

If you put in drugs, you can block things and push things one way or the other, but you can't read and monitor whats going on, said Wendell Lim, PhD, a professor of cellular and molecular pharmacology who directs the Cell Design Institute at UCSF. A living cell can get into the disease ecosystem and sense what's going on, and then actually try to restore that ecosystem.

Like people, cells live in communities and share duties. They even take on new identities when the need arises, operating through unseen forces that biologists term, self-organizing.

We need cells with GPS that never make mistakes in where they need to go, and with sensors that give them real-time information before they deliver their payload.

Hana El-Samad, PhD

Some living cell therapies could be controlled even after they enter the body.

Lim and others say it is possible to begin adapting cells into therapy, even when so much has yet to be learned about human biology, because cells already know so much.

Their built-in power includes dormant embryonic abilities, so a genetic nudge in the right place could enable a cell to assume a new function, even something it has never done before.

When a cell, a building block thats 10 microns in diameter can do that, and you have 10 trillion of them in your body, its a whole new ballgame, said Zev Gartner, PhD, a professor of pharmaceutical chemistry who studies how tissues form. Were not talking about engineering in the same way that somebody working at Ford or Intel or Apple or anywhere else thinks about engineering. Its a whole new way of thinking about engineering and construction.

For several years now, synthetic biologists have been building rudimentary feedback circuits in model organisms like yeast by inserting engineered DNA programs. Recently, Lim and El-Samad put these circuits into mice to see if they could tamp down the excess inflammation from traumatic brain injury.

They demonstrated that engineered T-cells could get into the sites of injury in the brain and perform an immune-modulating function. But its just a prototype of what synthetic circuits could do.

You can imagine all kinds of scenarios of therapies that dont cause any side effects, and do not have any collateral damage, said El-Samad.

UCSF researchers are building ever more complex circuits to move cells around the body and sense their surroundings. They hope to load them with DNA programs that trigger the cells protein-making machinery to do things like remove cancerous cells, then repair the damage caused by the tumors haphazard growth.

Or they could make cells that send signals to finetune the immune system when it overreacts to a threat or mistakenly attacks healthy cells. Or build new tissue and organs from our bodys own cells to repair damage associated with trauma, disease, or aging.

The fact that biological systems and cellular systems can self-organize is a huge part of biology, and thats something were starting to program, Lim said. Then we can make cells that do the functions that we want. We aspire to not only have immune cells be better at killing and detecting cancer but also to suppress the immune system for autoimmunity and inflammation or go to the brain to fight degeneration.

These UCSF scientists are on their way to engineering cell-based solutions to different diseases.

Tejal Desai, PhD, a professor and chair of the Department of Bioengineering and Therapeutic Sciences, is employing nanotechnology to create tiny depots where cells that have been engineered to treat Type 1 diabetes or cancer can refuel with oxygen and nutrients.

Having growth factors or other factors that keep them chugging along is very helpful, she said. Certain cytokines help specific immune cells proliferate in the body. We can design synthetic particles that present cytokines and have a signal that says, Come over to me. Basically, a homing signal.

Ophir Klein, MD, PhD, a professor of orofacial sciences and pediatrics, employs stem cell biology to research treatments for birth defects and conditions like inflammatory bowel disease. He is working with Lim and Gartner to create circuits that induce cells to grow in new ways, for example to repair the damage to intestines in Crohns disease.

Cells and tissues are able to do things that historically we thought they were incapable of doing, Klein said. We dont assume that the way things happen or dont happen is the best way that they can happen, and were trying to figure out if there are even better ways.

Faranak Fattahi, PhD, a Sandler Faculty Fellow, is developing cell replacement therapy for damaged or missing enteric neurons, which regulate the muscles that move food through the GI tract. She generated these gut neurons using iPS cell technology.

What we want to do in the lab is see if we can figure out how these nerves are misbehaving and reverse it before transplanting them inside the tissue, she said. Now, she is working with Lim to refine the cells, so they integrate into tissues more efficiently without being killed off by the immune system and work better in reversing the disease.

Matthias Hebrok, PhD, a professor in the Diabetes Center, has created pancreatic islets, a complex cellular ecosystem containing insulin-producing beta cells, glucagon-producing alpha cells and delta cells.

Now, he is working on how to make islet transplants that dont trigger the immune system, so diabetes patients can receive them without immune-suppressing drugs.

We might be able to generate stem-cell derived organs that the recipients immune system will either recognize as self or not react to in a way that would disrupt their function.

In health, the community of cells in these islets perform the everyday miracle of keeping your blood sugar on an even keel, regardless of what you ate or drank, or how little or how much you exercised or slept.

To me, at least, thats the most remarkable thing about our cells, Gartner said. All of this stuff just happens on its own.

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Beyond CAR-T: New Frontiers in Living Cell Therapies - UCSF News Services

Sleeper cells, cells of origin and hematopoietic stem cells – Brain Tumour Research

Firstly, two news items on glioblastoma that will be of particular interest to scientists at our Research Centre at Queen Mary, University of London. This brain tumour type is the most aggressive and most common primary high-grade tumour diagnosed in adults.

We begin with some fascinating research into a new stage of the stem cell life cycle could be the key to unlocking new methods of brain cancer treatment. Following brain stem cell analysis, through single-cell RNA sequencing, data mapped out a circular pattern that has been identified as all of the different phases of the cell cycle. A new cell cycle classifier tool then took a closer, high-resolution look at what's happening within the growth cycles of stem cells and identified genes that can be used to track progress through this cell cycle. When the research team analysed cell data for Gliomas, they found the tumour cells were often either in the Neural G0 or G1 growth state and that as the tumours became more aggressive, fewer and fewer cells remained in the resting Neural G0 state. They correlated this data with the prognosis for patients with Glioblastoma and found those with higher Neural G0 levels in tumour cells had less aggressive tumours. So, if more cells could be pushed into this quiescent, or sleepy, state tumours would become less aggressive. Current cancer drug treatments focus on killing cancer cells. However, when the cancer cells are killed, they release cell debris into the surrounding area of the tumour, which can cause the remaining cells to become more resistant to drugs. If, instead of killing cells, we put them to sleep could that potentially be a better way forward?

For the first time, scientists have discovered stem cells of the hematopoietic system in glioblastomas. These hematopoietic stem cells promote division of the cancer cells and at the same time suppress the immune response against the tumour so Glioblastomas. In tissue samples of 217 Glioblastomas, 86 WHO grade II and III Astrocytomas, and 17 samples from healthy brain tissue, researchers used computer-assisted transcription analysis to draw up profiles of the cellular composition. The tissue samples were taken directly from the post-surgery, resection margins - where remaining tumour cells and immune cells meet. The team were able to distinguish between signals from 43 cell types, including 26 different types of immune cells. To their great surprise, the researchers discovered hematopoietic stem and precursor cells in all the malignant tumour samples, while this cell type was not found in healthy tissue samples. An even more surprising observation was that these blood stem cells seem to have fatal characteristics: They suppress the immune system and at the same time stimulate tumour growth. When the researchers cultured the tumour-associated blood stem cells in the same petri dish as Glioblastoma cells, cancer cell division increased. At the same time, the cells produced large amounts of the PD-L1 molecule, known as an "immune brake", on their surface.

On diagnosis of an Ependymoma an adult is often treated with surgery followed by radiation. When a tumour comes back, there had been no standard treatment options. Recently, thats changed, thanks to results from the first prospective clinical trial for adults with Ependymoma, which showed the benefits of a combination regimen including a targeted drug and chemotherapy.

Also of relevance to our Research Centre at QMUL, a study may have identified the cell of origin of Medulloblastoma. Using organoids to simulate tumour tissue in 3D an approach also used by researchers at QMUL - this organoid model has enabled researchers to identify the type of cell that can develop into Medulloblastoma. These cells express Notch1/S100b, and play a key role in onset, progression and prognosis.

Research has been looking at how Medulloblastoma travels to other sites within the central nervous system and has shown that an enzyme called GABA transaminase, abbreviated as ABAT, aids metastases in surviving the hostile environment around the brain and spinal cord and in resisting treatment. These findings may provide clues to new strategies for targeting lethal Medulloblastoma metastases.

You can register to join an online lecture on the molecular analysis of paediatric Medulloblastoma and vulnerabilities, the development of models that recapitulate the patients diseases and how models allow to identify new therapies using a pre-clinical pipeline. It is on July 13th.

From the 12 15 of August you can watch The Masters Live World Course in Brain and Spine Tumour Surgery this event wont be streamed or saved on social media and registration is free.

Still focussing on neuro surgery this link takes you to a Neurosurgeon's guide to Cognitive Dysfunction in Adult Glioma

Grounds for optimism to end with as a prominent clinician/scientist believes Glioblastoma outcomes could change for the better soon. Frederick F. Lang Jr, MD, chair of neurosurgery at The University of Texas MD Anderson Cancer Centre, and a co-leader of the institutions Glioblastoma Moon Shot programme says I am optimistic that we are going to see changes in the survival as we start to [better] understand the groups of people we're treating, and as we separate out the tumours more precisely and classify them better. Then, as we understand the biology of [the disease] better and better, we're going to see changes in the near future terms of survival. The University of Texas MD Anderson Cancer Centre is pursuing several novel approaches, including viro-immunotherapy and genetically engineered natural killer cells to treat patients with GBM, while also conducting tumour analysis to better comprehend the disease.

Whether to find out more about the Glioblastoma tumour microenvironment work or research into Medulloblastoma carried out at our Queen Mary University of London (QMUL) centre, the techniques at the forefront of tumour neurosurgery being employed by Consultant Neurosurgeon Kevin ONeill at our Imperial College, London Centre or the work into Meningioma and Acoustic Neuroma ( Thursday was Acoustic Neuroma Awareness Day) that Professor Oliver Hanemann focuses on at our University of Plymouth Centre, it is always worth checking our Research News pages and for an overview of our research strategy check out Brain Tumour Research our research strategy.

Finally, a request for you all to support our #StopTheDevastation campaign click through, find out more, get involved and say #NoMore to brain tumours.

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Marker Therapeutics Announces Completion of Safety Lead-In Portion of Phase 2 Study in Post-Transplant AML – PRNewswire

HOUSTON, July 6, 2021 /PRNewswire/ --Marker Therapeutics, Inc.(Nasdaq:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, today announced completion of the six-patient safety lead-in portion of the Company's Phase 2 trial of MT-401, its lead MultiTAA-specific T cell product candidate, for the treatment of post-transplant acute myeloid leukemia (AML).

"We are pleased with the results of the safety lead-in portion of the trial, in which all six patients met the safety endpoints following infusion of our MultiTAA-specific T cell therapy," said Mythili Koneru, M.D., Ph.D., Chief Medical Officer ofMarker Therapeutics. "We are currently enrolling patients in the main portion of our first Company-sponsored trial and continue to activate clinical sites across the U.S. We are looking forward to further advancing MT-401 in this disease setting. Despite recent advances in how hematological malignancies are treated, patients remain in urgent need of new therapeutic options."

About Marker's Phase 2 AML Post-Transplant Study

The multicenter Phase 2 AML study is evaluating the clinical efficacy of MT-401 in patients with AML following an allogeneic stem-cell transplant in both the adjuvant and active disease setting. In the adjuvant setting, approximately 120 patients will be randomized 1:1 to either MT-401 at 90 days post-transplant versus standard-of-care observation, while approximately 40 patients with active disease will receive MT-401 as part of the single-arm group.

The primary objectives of the trial are to evaluate relapse-free survival in the adjuvant group and determine the complete remission rate and duration of complete remission in active disease patients. Additional objectives include, for the adjuvant group, overall survival and graft-versus-host disease relapse-free survival while additional objectives for the active disease group include overall response rate, duration of response, progression-free survival and overall survival.

InApril 2020, the FDA granted Orphan Drug designation to MT-401 for the treatment of patients with AML following allogeneic stem cell transplant.

About Marker Therapeutics, Inc.Marker Therapeutics, Inc. is a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications. Marker's cell therapy technology is based on the selective expansion of non-engineered, tumor-specific T cells that recognize tumor associated antigens (i.e. tumor targets) and kill tumor cells expressing those targets. This population of T cells is designed to attack multiple tumor targets following infusion into patients and to activate the patient's immune system to produce broad spectrum anti-tumor activity. Because Marker does not genetically engineer its T cell therapies, we believe that our product candidates will be easier and less expensive to manufacture, with reduced toxicities, compared to current engineered CAR-T and TCR-based approaches, and may provide patients with meaningful clinical benefit. As a result, Marker believes its portfolio of T cell therapies has a compelling product profile, as compared to current gene-modified CAR-T and TCR-based therapies.

To receive future press releases via email, please visit: https://www.markertherapeutics.com/email-alerts.

Forward-Looking StatementsThis release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Statements in this news release concerning the Company's expectations, plans, business outlook or future performance, and any other statements concerning assumptions made or expectations as to any future events, conditions, performance or other matters, are "forward-looking statements." Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: our research, development and regulatory activities and expectations relating to our non-engineered multi-tumor antigen specific T cell therapies; the effectiveness of these programs or the possible range of application and potential curative effects and safety in the treatment of diseases; the timing, conduct and success of our clinical trials, including the Phase 2 trial of MT-401; and the overall market opportunity for our product candidates. Forward-looking statements are by their nature subject to risks, uncertainties and other factors which could cause actual results to differ materially from those stated in such statements. Such risks, uncertainties and factors include, but are not limited to the risks set forth in the Company's most recent Form 10-K, 10-Q and other SEC filings which are available through EDGAR at http://www.sec.gov. Such risks and uncertainties may be amplified by the COVID-19 pandemic and its impact on our business and the global economy. The Company assumes no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

SOURCE Marker Therapeutics, Inc.

markertherapeutics.com

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Marker Therapeutics Announces Completion of Safety Lead-In Portion of Phase 2 Study in Post-Transplant AML - PRNewswire

A New Era For FDA Regulation Of Cell And Tissue Products – Law360

Law360 (July 1, 2021, 5:54 PM EDT) -- The May 31 expiration of the U.S. Food and Drug Administration's enforcement discretion period for the regulatory oversight of cell and tissue products, coupled with a June 2 decision in the U.S. Court of Appeals for the Eleventh Circuit, pave the way for the FDA to take more aggressive action against companies, clinics and individuals using cells and tissues to create FDA-regulated products.

The regulation of human cells, tissues, and cellular and tissue-based products, which fall within the larger category of products known as regenerative medicine, is a legally complex area fraught with both misperceptions and misunderstandings. It is therefore critical...

In the legal profession, information is the key to success. You have to know whats happening with clients, competitors, practice areas, and industries. Law360 provides the intelligence you need to remain an expert and beat the competition.

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A New Era For FDA Regulation Of Cell And Tissue Products - Law360

Cell Therapy Global Market Report 2021: COVID-19 Growth and Change to 2030 – ResearchAndMarkets.com – Business Wire

DUBLIN--(BUSINESS WIRE)--The "Cell Therapy Global Market Report 2021: COVID-19 Growth and Change to 2030" report has been added to ResearchAndMarkets.com's offering.

The global cell therapy market is expected to grow from $7.2 billion in 2020 to $7.82 billion in 2021 at a compound annual growth rate (CAGR) of 8.6%.

Major players in the cell therapy market are Fibrocell Science Inc., JCR Pharmaceuticals Co. Ltd., PHARMICELL Co. Ltd., Osiris Therapeutics Inc., MEDIPOST, Vericel Corporation, Anterogen Co. Ltd., Kolon TissueGene Inc., Stemedica Cell Technologies Inc., and AlloCure.

The growth is mainly due to the companies resuming their operations and adapting to the new normal while recovering from the COVID-19 impact, which had earlier led to restrictive containment measures involving social distancing, remote working, and the closure of commercial activities that resulted in operational challenges. The market is expected to reach $12.06 billion in 2025 at a CAGR of 11%.

The cell therapy market consists of sales of cell therapy and related services. Cell therapy (CT) helps repair or replace damaged tissues and cells. A variety of cells are used for the treatment of diseases includes skeletal muscle stem cells, hematopoietic (blood-forming) stem cells (HSC), lymphocytes, mesenchymal stem cells, pancreatic islet cells, and dendritic cells.

The cell therapy market covered in this report is segmented by technique into stem cell therapy; cell vaccine; adoptive cell transfer (ACT); fibroblast cell therapy; chondrocyte cell therapy. It is also segmented by therapy type into allogeneic therapies; autologous therapies, by application into oncology; cardiovascular disease (CVD); orthopedic; wound healing; others.

The high cost of cell therapy hindered the growth of the cell therapy market. Cell therapies have become a common choice of treatment in recent years as people are looking for the newest treatment options. Although there is a huge increase in demand for cell therapies, they are still very costly to try. Basic joint injections can cost about $1,000 and, based on the condition, more specialized procedures can cost up to $ 100,000. In 2020, the average cost of stem cell therapy can range from $4000 - $8,000 in the USA. Therefore, the high cost of cell therapy restraints the growth of the cell therapy market.

Key players in the market are strategically partnering and collaborating to expand the product portfolio and geographical presence of the company. For instance, in April 2018, Eli Lilly, an American pharmaceutical company entered into a collaboration agreement with Sigilon Therapeutics, a biopharmaceutical company that focused on the discovery and development of living therapeutics to develop cell therapies for type 1 diabetes treatment by using the Afibromer technology platform.

Similarly, in September 2018, CRISPR Therapeutics, a biotechnological company that develops transformative medicine using a gene-editing platform for serious diseases, and ViaCyte, a California-based regenerative medicine company, collaborated on the discovery, development, and commercialization of allogeneic stem cell therapy for diabetes treatment.

In August 2019, Bayer AG, a Germany-based pharmaceutical and life sciences company, acquired BlueRock Therapeutics, an engineered cell therapy company, for $1 billion. Through this transaction, Bayer AG will acquire complete BlueRock Therapeutics' CELL+GENE platform, including a broad intellectual property portfolio and associated technology platform including proprietary iPSC technology, gene engineering, and cell differentiation capabilities. BlueRock Therapeutics is a US-based biotechnology company focused on developing engineered cell therapies in the fields of neurology, cardiology, and immunology, using a proprietary induced pluripotent stem cell (iPSC) platform.

The rising prevalence of chronic diseases contributed to the growth of the cell therapy market. According to the US Centers for Disease Control and Prevention (CDC), chronic disease is a condition that lasts for one year or more and requires medical attention or limits daily activities or both and includes heart disease, cancer, diabetes, and Parkinson's disease.

Stem cells can benefit the patients suffering from spinal cord injuries, type 1 diabetes, Parkinson's disease (PD), heart disease, cancer, and osteoarthritis. According to Cancer Research UK, in 2018, 17 million cancer cases were added to the existing list, and according to the International Diabetes Federation, in 2019, 463 million were living with diabetes.

According to the Parkinson's Foundation, every year, 60,000 Americans are diagnosed with PD, and more than 10 million people are living with PD worldwide. The growing prevalence of chronic diseases increased the demand for cell therapies and contributed to the growth of the market.

Key Topics Covered:

1. Executive Summary

2. Cell Therapy Market Characteristics

3. Cell Therapy Market Trends And Strategies

4. Impact Of COVID-19 On Cell Therapy

5. Cell Therapy Market Size And Growth

5.1. Global Cell Therapy Historic Market, 2015-2020, $ Billion

5.2. Global Cell Therapy Forecast Market, 2020-2025F, 2030F, $ Billion

6. Cell Therapy Market Segmentation

6.1. Global Cell Therapy Market, Segmentation By Technique, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

6.2. Global Cell Therapy Market, Segmentation By Therapy Type, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

6.3. Global Cell Therapy Market, Segmentation By Application, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

7. Cell Therapy Market Regional And Country Analysis

7.1. Global Cell Therapy Market, Split By Region, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

7.2. Global Cell Therapy Market, Split By Country, Historic and Forecast, 2015-2020, 2020-2025F, 2030F, $ Billion

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/719lux

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Cell Therapy Global Market Report 2021: COVID-19 Growth and Change to 2030 - ResearchAndMarkets.com - Business Wire

UM School Of Medicine Researchers Receive NIH Avant Garde Award For Out-Of-Box, Innovative Concept To Cure HIV And Treat Co-Existing Addiction -…

Newswise University of Maryland School of Medicine (UMSOM) Professor of Diagnostic Radiology & Nuclear Medicine, Linda Chang, MD, MS, received the National Institute on Drug Abuse (NIDA) 2021 Avant Garde Award (DP1) for HIV/AIDS and Substance Use Disorder Research a National Institutes of Health (NIH) Directors Pioneer Award. This prestigious award supports researchers with exceptional creativity, who propose high-impact research with the potential to be transformative to the field. Her proposed project will involve a team of experts in brain imaging, infectious diseases, addiction, animal research, and gene-editing technology with the goal to essentially eradicate all traces of HIV from the body, and treat commonly co-existing substance use disorders. 2021 Avant Garde Awardees are expected to receive more than $5 million over five years.

I am extremely pleased, and feel very fortunate to have received this award, says Dr. Chang, who has a secondary appointment in the Department of Neurology at UMSOM. This project takes my work in a new direction. I believe my track record of being able to work across multiple disciplines with various researchers to initiate new areas of research and getting good results, along with the outstanding collaborators and resources at UMB, gave the proposal reviewers confidence that my team and I can significantly advance this new project.

About 38 million people around the world live with HIV, according to the Centers for Disease Control and Prevention. Although antiretroviral therapies can treat HIV to the point of undetectable viral levels and lead to long, healthy lifespans, these medications must be taken for life to prevent a resurgence, as HIV can hide from these drugs by integrating copies of itself into a persons genome. Once the drugs are stopped, the virus can reemerge.

From start to finish, Dr. Changs plan is to remove HIV from the genome, even in tough to reach spots like the brain, get more of the antiretroviral therapies into the brain, and stimulate the reward system in the brain to reduce drug cravings. The work will start out in mice before it can be tested in people.

Dr. Chang plans to use the gene-editing technology known as CRISPR to cut out copies of the hidden HIV genes in the genomes of mice, so they can be eradicated by antiretroviral drugs.

However, getting the CRISPR therapy into the brain can be difficult because of the blood-brain barrier, which protects the brain from infectious bacteria and foreign substances. The blood-brain barrier also prevents antiretroviral drugs from reaching high enough concentrations in the brain and central nervous system to effectively destroy HIV.

To seek out HIV in the brain, Dr. Chang and her team will temporarily disrupt the blood-brain barrier to allow more of the antiretroviral drugs or the CRISPR compounds to cross over the blood-brain barrier using an unique resource at the University of Marylandthe MRI-guided focused ultrasound system. This technique uses the MRI scan to help guide 2,000 pinpointed beams of high energy sound waves, along with microscopic bubbles, to non-invasively and temporarily open an area of the brain with the goal of eliminating the hidden reservoirs of virus in the brains immune cells.

About half of the people with HIV use substances, like drugs or alcohol, or have substance use disorders. Even tobacco or cannabis use in people with HIV is at 2-3 times that of the general population. Together with Victor Frenkel, PhD, an Associate Professor in the Department of Radiology and the Director of Translational Focused Ultrasound, and Donna Calu, PhD, Assistant Professor in the Department of Anatomy and Neurobiology, Dr. Chang will use low energy MR-guided focused ultrasound to suppress brain activity in the reward center of the brain, the nucleus accumbens. They hope this approach will suppress drug cravings in people with HIV who have substance use disorders.

The different components of this project will first be tested in mouse or rat models before moving onto clinical studies. As HIV does not normally infect mice, researchers use humanized mice that have weak immune systems, which are replaced with human blood stem cells that become human immune cells that can be infected with HIV. Although these humanized mice make lots of T cells a main cell for HIV infectionthey dont make the immune cells that HIV uses to hide in the brain, known as microglia. Recently, Dr. Changs collaborator Howard E. Gendelman, MD, Margaret R. Larson Professor of Internal Medicine and Infectious Diseases Chair at University of Nebraska Medical Center, and his lab created a modified humanized mouse that has an extra human gene that allows the human blood stem cells to now make microglia.

These new mice mean that these experiments can be done in a fraction of the time and cost and without the other hurdles that come along with using non-human primates, which are the only other animal that a special strain of HIV can infect, says collaborator Alonso Heredia, PhD, Associate Professor of Medicine and scientist at UMSOMs Institute of Human Virology.

He adds, There have been many attempts to eradicate HIV in the body, and it is thought they have not been successful, in part because we cannot get to the HIV reservoirs in the brain. If this works, we will be much closer to a practical cure for HIV. Dr. Heredia will be collaborating with Dr. Chang on this project using HIV-infected humanized mice that he has developed for his other ongoing projects.

For the addiction studies, Dr. Changs team will use the expertise and rodent models of addiction developed and optimized by Mary Kay Lobo, PhD, Professor of Anatomy and Neurobiology, and Dr. Calu. The mice will self-administer fentanyl, a powerful, synthetic opioid.

Dr. Frenkel and Dheeraj Gandhi, MBBS, Professor of Diagnostic Radiology and Nuclear Medicine and Clinical Director of Center of Metabolic Imaging and Therapeutics at UMSOM, are the teams MRI-guided focused ultrasound and clinical research experts.

My hearty congratulations to Dr. Chang and her colleagues and collaborators. If anything is called cutting edge this work surely qualifies for that praise. We wish this group all the success possible, said Robert C. Gallo, MD, The Homer & Martha Gudelsky Distinguished Professor in Medicine, Co-Founder and Director, Institute of Human Virology (IHV), University of Maryland School of Medicine, a Global Virus Network (GVN) Center of Excellence, and GVN Co-Founder and International Scientific Advisor.

Dr. Chang is an expert in using brain imaging to study how HIV or drug use affect the brain in adults and during adolescence, and how exposure to drugs in the womb affects childhood development. She has also conducted clinical trials for treating HIV-associated cognitive disorders and substance use disorders.

Dr. Chang joined UMSOM in 2017 through the Deans initiative Special Trans-Disciplinary Recruitment Award Program (STRAP). The STRAP Initiative was part of UMSOM's multi-year research strategy ACCEL-Med (Accelerating Innovation and Discovery in Medicine) to increase the quality and reputation of clinical and basic science research bringing UMSOM among other top-tier medical research schools.

Dr. Changs arrival to UMSOM spurred the exact kind of collaborative efforts we had hoped to foster through our recruitment program in order to accelerate discoveries, treatments and cures for the worlds most pressing diseases, says E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, UMSOM.I look forward to following her teams progress on this ambitious project in the hope that one day we can eradicate HIV.

Dr. Chang served on the National Advisory Council on Drug Abuse for NIDA and is a current member on the Council of Councils at the NIH.

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest-growing, top-tier biomedical research enterprises in the world -- with 45 academic departments, centers, institutes, and programs; and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research.

With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically-based care for nearly 2 million patients each year. The School of Medicine has more than $563 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 student trainees, residents, and fellows.

The combined School of Medicine and Medical System (University of Maryland Medicine) has an annual budget of nearly $6 billion and an economic impact of more than $15 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visitmedschool.umaryland.edu

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UM School Of Medicine Researchers Receive NIH Avant Garde Award For Out-Of-Box, Innovative Concept To Cure HIV And Treat Co-Existing Addiction -...

Antengene Announces Acceptance of IND Application in China for the Phase II Clinical Trial of Single-Agent Selinexor for the Treatment of…

SHANGHAI and HONG KONG, July 5, 2021 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in-class therapeutics in hematology and oncology, recently announced that China's National Medical Products Administration (NMPA) has accepted the Investigational New Drug (IND) application for single agent selinexor, a first-in-class orally available Exportin 1 (XPO1) inhibitor, for the treatment of patients with myelofibrosis (MF) in China.

MF is a clonal hematologic neoplasm which can emerge either as primary MF, polycythemia vera (PV) or essential thrombocythemia (ET)[1]. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment for MF. However, such treatment is difficult to carry out and has a low rate of success. According to the National Comprehensive Cancer Network (NCCN) Guidelines for the Treatment of MF, patients with intermediate-2 or high-risk MF ineligible for allo-HSCT and with a platelet count of 50109/L should be treated with ruxolitinib or fedratinib, while there are few follow-on treatment alternatives for patients failed or resistant to ruxolitinib. At present, only ruxolitinib has been approved for clinical treatment in China, and as a result, MF remains a disease with limited treatment options, representing an urgent unmet medical need.

This randomized, open-label, multicenter Phase II study is designed to evaluate the safety and efficacy of selinexor versus physician's choice (PC) in patients with MF who had at least six months of treatment with a JAK1/2 inhibitor. Approximately 112 patients with MF from 75 trial centers across the world will be randomized in a 1:1 ratio into one of the two treatment arms.

"This acceptance by the NMPA of the IND application for the China study of selinexor in patients with MF marks another major step forward in our effort to develop selinexor into a novel cancer drug. It also paves the way for our on-going exploration of additional indications for Antengene's novel assets," said Dr. Jay Mei, Founder, Chairman and CEO of Antengene. "We are hopeful that, through this novel drug candidate with strong potential in this disease, coupled with our deep expertise in the field of hematologic malignancies, we will be able to bring renewed hope to patients with MF in China. Moving forward, we will work closely with the NMPA to advance this trial in China, and strive to bring this innovative therapeutic to patients in the region and beyond."

About Selinexor (XPOVIO)

Selinexor is a first-in-class oral selective inhibitor of nuclear export (SINE) compound discovered and developed by Karyopharm Therapeutics Inc. (NASDAQ: KPTI), Selinexor is currently being developed by Antengene, which has the exclusive development and commercial rights in certain Asia-Pacific markets, including Greater China, South Korea, Australia, New Zealand and the ASEAN countries.

In July 2019, the US Food and Drug Administration (FDA) approved selinexor in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (RRMM) and in June 2020 approved selinexor as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (RR DLBCL). In December 2020, selinexor also received FDA approval as a combination treatment for multiple myeloma after at least one prior therapy. In February 2021, selinexor was approved by the Israeli Ministry of Health for the treatment of patients with RRMM or RR DLBCL and in March 2021, the European Commission (EC) has granted conditional marketing authorization for selinexor (NEXPOVIO) for the treatment of adult patients with RRMM.

Selinexor is so far the first and only oral SINE compound approved by the FDA and is the first drug approved for the treatment of both MM and DLBCL. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene's partner, Karyopharm, presented positive results from the Phase III randomized, double blind, placebo controlled, cross-over SEAL trial evaluating single agent, oral selinexor versus matching placebo in patients with liposarcoma. Karyopharm also announced that the ongoing Phase III SIENDO trial of selinexor in patients with endometrial cancer passed the planned interim futility analysis and the Data and Safety Monitoring Board (DSMB) recommended the trial should proceed as planned without any modifications. Top-line SIENDO trial results are expected in the second half of 2021.

Antengene is currently conducting five late-stage clinical trials of selinexor for the treatment of MM, DLBCL, non-small cell lung cancer, and peripheral T and NK/T-cell lymphoma. Furthermore, Antengene has submitted New Drug Applications (NDAs) for selinexor in multiple Asia-Pacific markets including China, Australia, South Korea, and Singapore, and was granted the Priority Review status by China's NMPA and an Orphan Drug Designation by the Ministry of Food and Drug Safety of South Korea (MFDS).

About Antengene

Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage R&D driven biopharmaceutical company focused on innovative medicines for oncology and other life threatening diseases. Antengene aims to provide the most advanced anti-cancer drugs to patients in the Asia-Pacific Region and around the world. Since its establishment in 2017, Antengene has built a broad and expanding pipeline of clinical and pre-clinical stage assets through partnerships as well as in-house drug discovery, and obtained 15 investigational new drug (IND) approvals and submitted 5 new drug applications (NDA) in multiple markets in Asia Pacific. Antengene's vision is to "Treat Patients Beyond Borders". Antengene is focused on and committed to addressing significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.

Forward-looking statements

The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

[1] J. Mascarenhas, B.K. Marcellino, M. Lu, M. Kremyanskaya, F. Fabris, L. Sandy, M. Mehrotra, J. Houldsworth, V. Najfeld, S. El Jamal, B. Petersen, E. Moshier, R. Hoffman, A phase I study of panobinostat and ruxolitinib in patients with primary myelofibrosis (PMF) and post-polycythemia vera/essential thrombocythemia myelofibrosis (post-PV/ET MF).

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Antengene Announces Acceptance of IND Application in China for the Phase II Clinical Trial of Single-Agent Selinexor for the Treatment of...

The Top Doctors in the Twin Cities, 2021 – Mpls.St.Paul Magazine

As medicine evolves with lightning speed, our medical community, built on a tradition of excellence, is taking a leading role in delivering transformative care. Local doctors are constantly shaping innovations that go on to become common practice and exploring new ideas about where care should be heading. The resultsimproved lives and outcomes, cutting-edge targeted treatments, and patient-centric care strategiesbenefit us all.

This year, as we celebrate the 25th edition of our Top Doctors list, we talked with professionals who have been on this list for decades and others newer to the ranks about the changes theyve seen and whats coming next in their fields. Read on to discover more than 800 local top doctors from 46 specialties who have been selected through a process involving extensive research and peer review.

See the complete list of doctors selected to this year's Top Doctors.

Theres much that is sobering about brain cancer: Glioblastoma (the most common type of brain tumor in adults) remains one of the deadliest cancers, and one of the most challenging to treat. Even with the most advanced care, it is a devastating disease. But patients today benefit from some major advancements of the past 15 years: Before 2005, there was no common standard for treating glioblastoma. Now, the protocol of surgery, radiation, and chemotherapy has extended life expectancyand much more is on the horizon. Im optimistic that before the end of my lifetime, we are going to see major changes for glioblastoma patients and achieve meaningful benefits, says Dr. Clark Chen. We asked him for his thoughts on the milestones in his field and whats giving him hope.

Surgically implanted radioactive seeds have the potential to improve life expectancy and quality of life for brain tumor patients.

Dr. Clark Chen

Why is brain cancer one of the most challenging/deadly cancers? The brain is a very different organ than the rest of the body. Our brain is so precious to us that our body has evolved barriers to protect it. For example, if you get food poisoning, your brain is protected from those toxins. And many chemotherapies are like toxins, so they cant get into the brain. Surgeons also have a very challenging task in figuring out how much of a tumor to remove, since one millimeter of difference could be the difference between the patient talking and understanding and not.

What improvements have been made in treatments over the past few decades? Surgically removing as much of a tumor as possible dictates how a patient will do. We have a number of tools to help with that, including MRI. But an MRI machine weighs tonsits not like you could easily bring it into the operating room. In the 1970s, the University of Minnesota started using one of the first intraoperative MRIs in the world, so we could do a surgery and bring in this state-of-the-art MRI and look in and know how much was removed during the surgery. It gives you real-time feedback. So surgeons could see when they could remove more and save a second surgery. That was a major, major milestone. We just installed the newest generation in 2019.

Another milestone allowing us to remove more of a tumor is a drug called 5-ALA. Its a drug that the patient drinks before surgery so that if you shine a blue light on the tumor, it will become fluorescent red. We were the first in the state, at the University of Minnesota, to have it during surgerywe started using it the moment the FDA approved it in 2017. Sometimes its very difficult to tell where the tumor ends, and this dye gives us that tool.

Im optimistic that before the end of my lifetime, we are going to see major changes for glioblastoma patients and achieve meaningful benefits.

Dr. Clark Chen

Also, surgically implanted radioactive seeds have the potential to improve life expectancy and quality of life for brain tumor patients. Picture cancer cells as unruly students, and the seeds as teachers. Having one teacher for 10,000 students is not going to work. But after a surgeon removes the majority of the cancer cells, the seed can be used to destroy the microscopic cells that are invisible to the naked eye. Because of its short range, which is five to eight millimeters, the radiation is concentrated in the region of the tumor and does not affect the rest of the brain. In the old days, the patient would have had to go back to the operating room if the tumor grew back after surgery.

When will immunotherapy be able to be used in brain cancer? Injection of a genetically engineered virus into glioblastomas will solicit immune responsesresponses that can be further enhanced with the immunotherapy that was awarded the 2018 Nobel Prize. Tumors that tend to benefit from immunotherapy are known as hot tumors. They are tumors with a lot of immune cells in there already; thats why theyre called hot. Cold tumors are ones that dont have a lot of immune cells. So a really exciting thing that we are doing is to surgically inject this virus into a cold glioblastoma that is devoid of immune cells and does not respond to immunotherapy and convert the tumor into a hot glioblastoma that responds to immunotherapy. In this way, we can engage the patients innate immune system to fight off the tumor cells. People have survived beyond expectation, but it doesnt work for everybody. Were trying to figure out why it works for some and not others. We are beginning to see extraordinary responses, and with each extraordinary response, we are one step closer to a cure for every patient. S.M.E.

Dr. Brian Swiglo, an endocrinologist with Allina Health, specializes in the treatment of conditions related to hormones and their effects on the bodys organs. Two-thirds of his practice is devoted to the treatment of people with diabetes.

Its been standard procedure for many people with type 1 diabetes to check their glucose levels with a finger stick about four times a day. However, modern technology is changing all of that. Dr. Brian Swiglo says that continuous glucose monitors are replacing finger sticksand theyre doing a much better job. Abbott, Dexcom, and Medtronic make small wearable devices (FreeStyle Libre, Dexcom G6, and Guardian Connect) that adhere to your arm or stomach and automatically read your blood sugar levels every 5 to 10 minutes. Then the information is sent to your phone or device. For people taking insulin, this is a huge boon. You really need that information in order to choose the right dose, Swiglo says. They can just look at their phone and know, Oh, Im 220. Well, now I need an extra three units on top of what I take for my food. It helps them dose their insulin a lot more accurately.

This knowledge is powerful, both for the patient, who gets a better understanding of how their glucose levels are affected by certain foods, activity, and insulin, and for the endocrinologist, who gets a better understanding of their patients meal and exercise habits. When were in clinic with them, we can download that information, look at it, and make more accurate adjustments in their insulin regimen, Swiglo says.

Insulin pumps have been around for about 30 years and are now being replaced with closed-loop insulin pumps, which talk to continuous glucose monitors. Its a huge step toward an artificial pancreas, Swiglo says. And its giving people greater freedomespecially at night. The biggest advantage is when someone goes to bed, they can fall asleep and sleep through the night while still having good control. Thats because the pump and the monitor are in constant communication and making any needed adjustments.

The newest medicines for type 2 diabetes can do more than lower a persons blood sugar. Theyre helping with weight loss and lowering the risk of cardiovascular disease. Most people with type 2 diabetes struggle with their weight, Swiglo says. So anything we can do to help them with weight loss is a benefit. J.J.

A cardiologist since the 1990s, Dr. Pamela Paulsen has worked at all three Level 1 trauma centers in the Twin Cities. After starting her career at Hennepin Healthcare, she moved to North Memorial Health Hospital for 17 years, and shes now with Regions Hospital. She also started the first womens heart clinic in Minnesota, which she ran for 10 years. Paulsen has cared for patients in acute emergency situations. Today, she practices all areas of general cardiology.

Dr. Pamela Paulsen completed her fellowship training in interventional cardiology at the University of Minnesota more than 25 years ago. We had reasonable treatment in 1994, but its unbelievably different now for patients, Paulsen says. Its our advancements in preventionbut also in heart attack carethat really revolutionized during the time I have been a cardiologist.

A combination of technological advancements and medications are helping to reduce heart disease and death from heart disease. Paulsen lists the three biggest game changers, the first of which is the use of stents. The ability to treat heart attack and chronic coronary artery disease with revascularizationor restoring blood flow predominantly through stentsreplaced a more invasive approach and had excellent outcomes, she says. Bonus: Todays stents come in all sizes and are drug-coated so that they are less likely to narrow as time goes on.

The second is the less invasive method now used to replace aortic heart valves. Transcatheter aortic valve replacement (TAVR) is performed by creating a small incision in the chest or using a blood vessel in the leg rather than through open-heart surgery. Advanced imaging guides a catheter to the aortic valve, where a new valve is positioned with the help of an inflated balloon. Its the preferred strategy for replacing aortic valves when theyre narrowed, Paulsen says.

Lastly, statins followed by injectable cholesterol drugs have significantly helped lower the risk of heart disease altogether. Since the 1970s, the risk of death from heart disease is down an average of 60 percent in the United States.

Paulsen is hopeful that the wave of the future will include incorporating personalized medicine in heart care that would pinpoint the best drugs and diet for an individual. She also is encouraged by the future potential of wearable technology for monitoring blood pressure, heart rhythms, and sleeping patterns and helping doctors care for patients. J.J.

In the 20 years that Dr. Gigi Chawla has been practicing as a pediatrician, advancements have fundamentally altered childrens health care experiences. If you still call a well-child visit a yearly checkup, heres a glimpse into the way todays parents and children experience the doctors office. First, new routine childhood immunizations for rotavirus, approved in 2006 and 2008, mean parents have one less thing to fret about. Hospitalizations from severe gastroenteritis, caused by rotavirus, have almost been eliminated. Kids would have serious morbidity, and some would die with the rotavirus, says Dr. Chawla, recalling the days when wards of kids would be hospitalized with the disease every winter.

With every scientific breakthrough, we have to think about how we apply those breakthroughs. This piece has got to be elevated.

Dr. Gigi Chawla

And COVID-19 vaccines may have a similar impact, she predicts. Even though most children dont experience serious illness from COVID-19, the technology used to create the Pfizer and Moderna vaccines could be applied to vaccine development for other illnesses, such as respiratory syncytial virus (RSV), a common respiratory virus that can hit infants hard, she says. That will also change the face of how pediatric illness is experienced, she says, explaining that RSV is the number one cause of childhood hospitalizations in winter.

But the COVID vaccines also revealed a negative side, highlighting disparities in health careand further accentuating them, Chawla says. Its not going to do us much good to have these breakthroughs if all it does is divide the haves and have-nots, she says.

Chawla has devoted the past three years to better understanding disparities in immunization rates between patients of color and white patients. With every scientific breakthrough, we have to think about how we apply those breakthroughs, she says. This piece has got to be elevated.

Its something Chawla thinks about constantly, she says, working to help health care overcome generations of institutional racism. Looking at vaccine disparity, for example, reveals a gap of 40 percent between Black and white patients in completion rates of the entire routine vaccination series before age 2, she found. For me, the first step is really understanding that vaccine disparity, which has likely been present during my entire career and weve just never been brave enough to look at it or willing as clinicians to understand what our role is in mitigating it, she says. To close the gap, Childrens Minnesota has implemented drive-up vaccination and mobile vaccination clinics and recognized other access hurdles, including the ability to make an appointment during clinic hours and to speak a language understood by front desk staff and providers, as well as the ability of clinicians to earn a patients trust.

Another important shift thats happened over Chawlas career, she says, is a recognition of just how important early childhood development is, as well as understanding the science behind it. Understanding how critical that bonding is with a trusted adult/caregiver/parent, and really engaging infants, toddlers, and young children in experiencing and exploring the worldincluding facilitating early language development, she says. There are 700 neural connections being made every second. Its immense. The time and energy we can all put into things like early language development pay off in multiple ways, including decreasing educational or opportunity gaps, which has inspired her to serve as Reach Out and Read Minnesotas Medical Director.

Childrens Minnesota and others have also integrated behavioral health into routine pediatric exams. Therapists, psychologists, and social workers are available during well-child and primary care visits should families need them. And given the high impact social determinants beyond the clinic have on kids healthwhere they live, learn, and playprimary care appointments at Childrens Minnesota now include screening for food insecurity, educational needs, housing concerns, and legal issues. After witnessing the value of this more comprehensive approach to caring for children, Chawla notes, Hopefully, every health care organization is working toward families experiences. S.M.E.

Dr. Mohamed Hassan has spent his nearly 32-year career specializing in gastroenterology and hepatology (diseases of the liver). In the last 17 years, he has also been practicing transplant hepatology. Today, he practices at M Health Fairview Clinics and Surgery Center in Minneapolis and M Health Fairview Clinics and Specialty Center in Edina.

More than 30 years ago, Drs. Harvey Alter, Michael Houghton, and Charles Rice identified the hepatitis C virus. In 2020, they received the Nobel Prize for their discovery. That was a big deal because hepatitis C went from not being known before 1989 to a disease that can easily be treated more than 93 percent of the time with direct-acting antiviral agents (DAAs), says Dr. Mohamed Hassan.

The field of liver transplantation has also made great strides since the first successful procedure in 1967. These days, a liver donor doesnt need to have a perfect bill of health. Patients in need of a liver transplant can even receive a good-functioning liver from a donor who has the hepatitis C virus. There are people who are very sick and cannot wait for a negative hep C liver or donor, Hassan says. After the transplantation is complete, the latest DAAssuch as sofosbuvirtreat the hep Cpositive liver. That is really remarkable and probably one of the best things thats happened. Hassan hopes in the near future there will be medications that can eliminate hepatitis B, a disease more likely to affect people born in Southeast Asian and African countries. It is now being tested, he says.

Hassan enjoys helping others, and his influence reaches beyond the clinic with the work he does in the local Somali community. Recently, to help build trust around the COVID-19 vaccine, Hassan was in a video with an imam at a mosque getting the vaccine. A lot of people gave me feedback and told me it did work, he says. Even family and friends back in Somalia saw the video in their community. J.J.

Back in 1990, Dr. John Wagner conducted the first-ever cord blood transplant for a leukemia patient. Now, he looks back on those early days of transplant medicine and exploration of the potential of cell therapies as a preamble to a future with endless possibilities for treating all types of diseases: manipulating cells to do what doctors and scientists want them to do. Whether you call it immunotherapy or precision or personalized medicine, Wagners work is on the fast track to curing some types of cancer.

What has been the biggest game changer in your specialty in the last few decades? Engineered cells, living drugs that can last in the body for days or a whole lifetime. One example is the use of genetically modified immune cells that specifically target a cancer. I became involved in the mid-80s during my training at Johns Hopkins School of Medicine, when we first started working with bone marrow for transplantation, but weve learned how to engineer cells more precisely since then.

Today, we can take cells from a sample of blood or skin biopsy and generate cells called induced pluripotent stem cellsreplacing the need for embryonic stem cells.

Dr. John Wagner

Has your work ever yielded any unintended results with a positive impact? A decade and a half ago, we thought that the embryonic stem cell was the only way you could make the various tissues of the body. Today, we can take cells from a sample of blood or skin biopsy and generate cells called induced pluripotent stem cells (IPSC)replacing the need for embryonic stem cellscells which can be used to test drugs and other treatments as well as repair damaged tissues. For example, our lab is working on using IPSC to make a nearly endless supply of blood-forming stem cells from a small sample of blood. You wont need any other donors, potentially.

What advancements are on deck? Even though the current approach is very effective, I cant tell when a patient with leukemia is going to come in the door and then everything stops to make it happen. Say you had leukemia. First, wed have to give chemotherapy to beat down the number of leukemia cells so that sufficient numbers of normal T cells can be collected for genetic engineering. It takes a month for manufacturing and testing the cell therapy before it is shipped back to the hospital where they give it to you. There are a couple of problems with that. One, you have to have chemo. Two, its an individual product for every single patient. That makes it logistically challenging and much more expensiveand you might not have a month. Many people are lost while waiting for the manufacturer. My guess is we may, for the first time, be able to cure cancer without using chemotherapy, radiation, or surgery. Thats the path were pursuing. So when youre diagnosed with leukemia, we will be able to forget about the traditional way of treating it and use cell therapy as the only treatment. Thats what we hope to move forward in the next one to two years. And we could move it into other fields . . . cardiology or multiple sclerosis or brain injury. All are in development with the same concept of taking a cell and modifying it to do what we want. This is going to be the game changer, and its sitting on the shoulders of the work of the prior 30 years.

How do these advancements impact previously overlooked or underserved communities? In the past, getting patients to take advantage of new advancements was more of a passive process. If you had a specific disease and you figured out how to get to the University of Minnesota and to me, I would check to see if you met the eligibility requirements and treat you. Today, we go to much greater lengths to find patients and make sure they know what is available, potentially, to them. We want to make sure the patients being enrolled into clinical trials appropriately reflect the makeup of our larger communitythat is, we want to ensure that we have people of all races and ethnicities.

One example: We want to develop off-the-shelf, cryopreserved products. Youd make them all in advance, and theyd be immediately available. Otherwise, some treatments, like immunotherapy, when manufactured as individual products, may never be available for the majority because of logistics and expense. But if I could take one sample of starting material and make 1,000 or more products and verify their potency in advance, we could send them anywhere in the world and people could get it the day theyre diagnosed.S.M.E.

Dr. Siobhan Flanagan is an interventional radiologist at University of Minnesota Health (M Physicians) who does minimally invasive procedures under imaging guidance. She treats liver cancer, vascular malformations, aortic aneurysms, peripheral arterial disease, and more.

University of Minnesota physician Kurt Amplatz helped invent interventional radiology more than three decades ago when he created a small plug-shaped medical device that could be passed through a catheter from the leg to the heart, thus repairing an atrial septal defect (hole in the heart) and avoiding open-heart surgery. Today, Dr. Siobhan Flanagan continues to move the field forward by providing targeted treatments to patients with serious medical problems, including liver cancer. If we can treat patients liver cancers effectively, we can then bridge them to transplant, Flanagan says.

With the help of a catheter and x-ray guidance, the treatment is injected directly into the artery that leads to the liver. As opposed to chemotherapy that circulates all throughout the body, were targeting the treatment just where it needs to go: the local blood supply to the tumor, Flanagan says. And thats especially great news for people with a liver tumor thats less than three centimeters. We can cure tumors less than three centimeters with some specific treatments and control tumors larger than three centimeters with a local therapy.

Compared to cancer, an abscess that develops in the abdomen after surgery might seem like an easy fix. But its not for a surgeon who has to navigate an area that was recently operated on and has a lot of inflammation. Thankfully, an interventional radiologist can come to the rescue. We can place an abscess drain under CT or ultrasound guidance to help drain the infected fluid so the patient doesnt have to have another operation, Flanagan says.

Vascular malformations, abnormal groupings and developments of blood vessels throughout the body, can also be treated with this technology. A lesion can be biopsied to test its genetics and determine which medication will help shrink it.

Flanagan is excited to see whats on the horizon in terms of personalized medicine, especially with tumor-specific therapy, determined by tissue receptors and genetics. Theres this continued opportunity for us to be involved with these treatments by delivering them directly to a tumor, she says. J.J.

Dr. Charles E. Crutchfield III practices dermatology at his clinic in Eagan, where he sees patients for the treatment of a variety of medical and cosmetic conditions. He also teaches dermatology to medical students, residents, and other clinical physicians at the University of Minnesota, Carleton College, and around the world.

Crutchfield has made it his mission to share the knowledge he has with others, including those in the medical field. Skin conditions in skin of color can look a lot different than what were trained on. So I coauthored a textbook of dermatology and made sure to include over 3,000 photographs, half of them in skin of color. He also covers the topic in lectures at the University of Minnesota and around the country. And he writes a weekly health column for the Minnesota Spokesman Recorder, the oldest Black newspaper in the state of Minnesota. Were doing our part to educate and further the knowledge in treating skin of color, he says.

Crutchfield is excited about the advances he sees in the treatment of various skin conditions. Were seeing treatments now for psoriasis, atopic eczema, and vitiligo that are extraordinarily effective for treating skin and inflammatory conditions in the human body, he says. They are changing the lives of our patients, he says.

And the advancements in aesthetic dermatology are also big game changers. Hyaluronic acid fillers and Botox injections rejuvenate the skin with natural-looking results. Crutchfield estimates he does 5 to 10 aesthetic treatments a day. And many of his patients will express to him that they wish they would have done the treatment years ago. I tell them, Well, we couldnt have done it years ago because we didnt have it, but we have it now. And well use it moving forward.

As everyone learned in 2020, COVID-19 created a paradigm shift in the delivery of care. And physicians had to pivot their practices to meet the needs of patients in a safe manner. These days, telehealth visits make up 30 to 40 percent of Crutchfields appointments. A year and a half ago, I had not done one telehealth visit, he says. And now Ive done 10,000-plus. Its surprising how much can be covered in a visit with a dermatologist via a webcam. Platforms such as Zoom, FaceTime, and Google Duo have great clarity of picture for medical evaluations and discussions. Crutchfield uses them for triage purposes, follow-up visits, and prescription refills. This will be part of our practice moving forward, he says. Patients love it, and I like it too.

After more than two decades of being the doctor, Crutchfield is now the patient. In early 2021, he was diagnosed with non-Hodgkins lymphoma, for which he is currently receiving treatments at the Mayo Clinic in Rochester. And the cancer treatment he has received has a medical legacy that ties back to early efforts by friends in the medical community. I have colleagues that were on the development team at Genentech 30 years ago that helped develop the [monoclonal antibody treatment] thats being used to treat me right now, Crutchfield says. My friends are so delighted that the medicine they helped develop is actually helping their friend. J.J.

Back when Dr. Elizabeth Arendt was playing sports in her first few years of college, the training room was only for male athletes. When Arendt or a female teammate got injured, they went to student health services, where ankle sprains were sometimes mistakenly treated with a hot-water bath.

Arendt, who played everything growing up, from Ping-Pong to horseshoes, competed in varsity volleyball and basketball in college in the early days of Title IX, the federal civil rights law aimed at preventing discrimination based on sex in education. As a premed student studying biology and anatomy, she was encouraged by administrators to fill a gap in the training room by treating female athletes. By her senior year, she was a student athletic trainer, challenging inequities in the newly coed training room. This experience not only motivated her to work to change the culture of athletics at the University of Rochester in New York; it also inspired her to pursue orthopedics and sports medicine instead of pathology, she says.

Research suggests that simple warm-up exercises can drastically lower the risk of ACL injuries.

Dr. Elizabeth Arendt

The world of orthopedic surgery is heavily male-dominated. In a 2015 survey, according to the Association for American Medical Colleges, 95 percent of orthopedic surgeons were male. The field is also lagging in diversity as a subspecialty field, but that is improving, Arendt says. But since graduating from medical school in 1979, shes seen some shift in the way athletic injuries are viewed in the field, placing less emphasis on gender.

When it was first discovered that females tear their anterior cruciate ligaments (ACL) more than males, some doctors theorized this was related to the hormonal environment due to menstrual cycles. While that hasnt been ruled out conclusively, theres much more evidence linking the risk to anatomic risk factors present in both sexes and body movement patterns, Arendt says. I think the focus has been less on the sex of the patient and more on what it is that characterizes knee injuries, says Arendt, who conducts research in the area.

This has led to a better understanding of acute injuries to the ACL and the patellofemoral joint, including an increased recognition of risk factors such as body movement patterns and anatomy in other musculoskeletal injuries. And thats helpful because smart training and coaching can reduce the risk of injury. Research suggests that simple warm-up exercises can drastically lower the risk of ACL injuries, for example.

The biggest change across knee surgeries, however, is probably the push toward outpatient surgeries. Ultimately, Arendt says, the shift comes with pros and cons, but to optimize the experience, patients should understand their insurance plans more than most do. For example, even patients who stay in the hospital overnight may be counted as outpatient surgeries, she says, meaning they dont qualify for a skilled nursing facility and would be expected to complete physical therapy with in-home physical therapy or on an outpatient basis.

And, love it or hate it, the biggest change in medicine in the past 30 years is the advancement of electronic medical records (EMR), she says, recalling the days of taking charts home to work on at night. From the patients perspective, there are clear benefits.

As much as it burdens us, theres no doubt the ability to document a patients pertinent information electronically and share it across medical systems is a huge improvement, she says. And its greatly improved our ability to deliver service at all hours. S.M.E.

Dr. BJ Harris specializes in gynecology and urogynecology at Womens Health Consultants and the Pelvic Floor Center.

In her 21-year career, Dr. BJ Harris has witnessed many gynecological and medical game changers. One of the big ones is the reduction in the number of hysterectomies, which used to be much more common and not always a medical necessity. Today, she says, minimally invasive hysteroscopies allow doctors to manage many issues in the uterus, such as abnormal bleeding and the removal of polyps and some fibroids. Also, some types of IUDstypically used for contraceptionhave been FDA-approved to help mitigate heavy bleeding. And tranexamic acid, originally prescribed to women to help make their periods less heavy, is now being used to help reduce blood loss from C-sections or other big surgeries, she says.

Other discoveries, such as the fact that some of the more aggressive types of ovarian cancers can begin in the fimbriae (fingers) of the fallopian tubes, help women make decisions about how to manage their long-term health. So, if one of Harriss patients is having a procedure, like removing an ovarian cyst, and this person is not planning on having (more) children, Harris also recommends removing the patients fallopian tubes at the same time. The fallopian tubes have never provided any hormone in the past, and they never will in the future, she says. All they provide is a cancer risk once women are done childbearing.

The majority of her practice focuses on patients with pelvic floor issues, such as vaginal prolapse or urinary incontinence. She helps them assess treatment options. For those with incontinence, she says, I do quality-of-life surgeries. One womans quality of life versus another womans is very different. I have some people that leak urine like a sieve, and they dont want surgery. And I have other people that say, I leaked twice at my aerobics class last week and I want surgery yesterday. She helps these individuals weigh risks and find healthy solutions and alternatives if they dont want surgery. J.J.

Dr. Mumtaz Kazim grew up watching her parents take care of patients in their 17-bed hospital on the island of Trinidad. She went to college in Canada and med school in India. Shes seen plenty of changes in health care in her career as a physician in the field of family medicine and as president of Edina Family Physicians.

What has been the biggest game changer in your specialty in the last 20 to 25 years? You said game changer, but maybe youll allow me three! The first everyone will agree with: EMR. Its increased access and ability to share information with specialists, allowing for better communication for multidisciplinary care. Also, the concept of what has happened with outpatient clinics. Edina Family Physicians used to be an independent family practice; most of these are now being purchased by larger systemsEdina Family Physicians is now affiliated with Allina. Its a big change. Then theres the concept of virtual visits. With COVID, our clinic was closed for a while, except for emergency care and phone calls, and you cant imagine the expressions of patients who were so lonely. When you see each other face-to-face, there is such delight to talk to somebody. And you can call back to check up on them. It was very helpful. It shouldnt be used for all medical care, but when they cannot come in, seeing them face-to-face in their own home gives you a whole different perspective.

I believe the increased number of women and minorities in all medical fields has had a positive impact on patient care.

Dr. Mumtaz Kazim

Whats the most exciting advancement just around the corner in family medicine? Personalized medicine, including genomic sequencing to target drugs for certain diseases, immunologic approaches to treat cancer, and CRISPR, which is a technology that adds or deletes genes to improve and cure medical conditions. It will help to improve the medical health of the community from sickle cell disease to diabetes and various cancers. Think about it, how great it would be if we could cure diabetes.

How has the diversity of our medical community changed things, and how have advances impacted previously overlooked or underserved communities? I believe the increased number of women and minorities in all medical fields has had a positive impact on patient care. Providers are so much more sensitive to disparities in the medical services available nowso much more than 30 years ago. I think that will eventually have a positive effect on delivery of care to underserved communities. And with the continuity of care now with EMR, we can provide better tracking of patients. Even though EMR is far, far from perfect (this is not an ad for it!), it provides us a tool to have continuity of care. And access to previous medical records is a tremendous help. For example, take the case of a patient who has mental health issues, in addition to some dementia, and no family in the Twin Cities. Hes gone to different emergency rooms and been seen by different providers across all of the systems. We have the EMR, and we can then get access to some of those records, which will then educate me on what has been happening.

Patients dont always offer a detailed medical history, and many patients, especially with cardiac disease, get shipped from one hospital to the next. So we may have patients with records from Abbott and then Southdale, and by the time they come back to me, I can check all of it. Thats very important because doctors shuffle around medications and dosages all the time, and cardiac patients are often on 6 to 10 medications.S.M.E.

Dr. Marjorie Hogan is a pediatrician at Hennepin Healthcare whos been caring for the needs of infants, children, adolescents, and young adults for 41 years.

When Dr. Marjorie Hogan started her practice in 1980, office visits typically involved the usual litany of questions regarding nutrition, sleep, and vaccines. Since then, pediatric careand the worldhas become much more complicated. We used to think brain development stopped sort of abruptly in childhood, but thats not the case, she notes. The brain continues evolving and maturing and arborizing and getting more complex and wonderful in many kids up to their 20s.

One of the dramatic shifts she has seen recently is in the number of school-aged children and teens expressing feelings about anxiety, fear, and stress, Hogan says. Thankfully, during these unprecedented times, providers like Hogan can put patients and their families in touch with a team of resourcesincluding nurses, social workers, educators, community health workers, and morethat will support the whole health of the child. However, she says, We need more mental health providers for children and teens. Its a crisis. It impacts every part of their lives. I am seeing more teensboth male and femalegrapple with eating disorders, with the risk of self-harm, [and] with substance abuse.

One of the complicating factors in the struggle: media. Back in the 80s, Hogan authored some of the first American Academy of Pediatrics (AAP) media statements that recommended parents limit childrens TV watching to less than 2 hours a day. Today, young people have access to more media than ever. In this past year, theres not one family Ive seen that has not had concerns about their childrens screen time and media use. Hogan recommends that parents be good media role models and develop a family plan. That means no electronic devices at the dinner table and certain shows and games should be off-limits. Be aware of what your children are watching or using as much as you can.

In recent years, the medical community has become more aware of the role that social determinants and inequities play in a childs overall health. Hogan is pleased that todays medical students and residents take courses on the topic so they can be better prepared to help children in a changing world. J.J.

See the complete list of doctors selected to this year's Top Doctors.

The 25thedition of our Top Doctors list includes 816doctors in 46specialties. Heres how we put it together. When compiling a list thats as relied upon as our annual Top Doctors list, research is essential. We asked physicians to nominate one or more doctors (excluding themselves) to whom they would go if they or a loved one were seeking medical care. From there, candidates were grouped into 46specialties and evaluated on myriad factors, including (but not limited to) peer recognition, professional achievement, extensive research, and disciplinary history. Doctors who had the highest scores from each grouping were invited to serve on a blue-ribbon panel that evaluated the other candidates. It should be noted that doctors cannot pay to be included on this list, nor are they paid to provide input. Only doctors who acquired the highest total points from the surveys, the research, and the expert physician review panel were selected to this list. Of course, no list is perfect. Many qualified doctors providing excellent care are not included on this years list. However, if youre looking for exceptional physicians who have earned the confidence and high regard of their peers, you can start your search here.In addition, this years crop of Top Doctors will join a prestigious group of doctors from more than 20 cities around the country who have been selected to Super Doctors, the full list of which you can find at superdoctors.com.

Editors Note: Many of our Top Doctors have specialty certification recognized by the American Board of Medical Specialties. This board certification requires substantial additional training in a doctors area of practice. We encourage you to discuss this board certification with your doctor to determine its relevance to your medical needs. More information about board certification is available at abms.org.

2021MSP Communications. All rights reserved. Super Doctors is a registered trademark of MSP Communications. Disclaimer: The information presented is not medical advice, nor is Super Doctors a physician referral service. We strive to maintain a high degree of accuracy in the information provided. We make no claim, promise, or guarantee about the accuracy, completeness, or adequacy of the information contained in the directory. Selecting a physician is an important decision that should not be based solely on advertising. Super Doctors is the name of a publication, not a title or moniker conferred upon individual physicians. No representation is made that the quality of services provided by the physicians listed will be greater than that of other licensed physicians, and past results do not guarantee future success. Super Doctors is an independent publisher that has developed its own selection methodology; it is not affiliated with any federal, state, or regulatory body. Self-designated practice specialties listed in Super Doctors do not imply recognition or endorsement of any field of medical practice, nor do they imply certification by a Member Medical Specialty Board of the American Board of Medical Specialties (ABMS) or that the physician has competence to practice the specialty. List research concluded April 19, 2021.

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The Top Doctors in the Twin Cities, 2021 - Mpls.St.Paul Magazine

Case study: Use of platelet-rich plasma and bone marrow …

April 21, 2018

The patient is a fit 83-year-old who, as a former flight attendant, is used to being on her feet. In 2014, she presented with osteoarthritis pain that started to affect her left knee and threatened her mobility, and she was searching for treatments that wouldn't interfere with her active lifestyle.

In January 2015, the patient had received two separate injections of platelet-rich plasma (PRP). The PRP injections alone did not provide adequate symptom relief. In July, she received an injection of bone marrow aspirate concentrate (BMAC) and PRP.

Jay Smith, M.D., a physiatrist and the director of Regenerative Medicine within the Rehabilitation Medicine Research Center at Mayo Clinic's campus in Rochester, Minnesota, evaluated the patient and administered the BMAC and PRP injections. To date, Dr. Smith and colleagues at Mayo have administered PRP or BMAC injections in more than 400 patients. Current scientific literature indicates that between 40 and 70 percent of individuals who receive this treatment find some level of pain relief, according to Dr. Smith. "It doesn't work 100 percent of the time," he says. "But we have a pretty good success rate when the primary goal is to improve symptoms and allow patients to do the things they want to do."

Dr. Smith says that a portion of the conversation he has with patients is that regenerative medicine strives to restore health by harnessing the body's natural ability to heal itself. "We tell our patients that it's an acceptably safe orthopedic procedure, and it may or may not modify their level of pain," Dr. Smith says.

What is known about the treatments is that they most likely lessen the inflammatory process caused by degrading joint cartilage. "Treatment with PRP is built upon the knowledge that platelets carry a multitude of growth factors," Dr. Smith says. "They are the first responder cells when we get injured, and they control the damage and start the healing process."

For PRP therapy, platelets are extracted from a vein in the patient's arm and concentrated using a centrifuge. The concentrate is then injected back into the patient's joint, where the growth factors mitigate inflammation.

BMAC contains not only platelets but also a variety of other powerful cells, including stem cells. Stem cells also have significant anti-inflammatory properties and can powerfully influence other cells involved in inflammation and healing. They also have the ability to become other types of cells. The bone marrow is drawn from a patient's pelvic bone, concentrated in a centrifuge and then injected into the problematic area. "The bone marrow concentrate and platelet rich plasma very naturally modify the inflammatory and immune response," Dr. Smith says.

A few hours after receiving treatment, the patient walked out of the procedure room with the aid of crutches and a knee brace, which she used for one week. The patient indicated that the injections eased the pain enough for her to return to her previous level of activity.

Dr. Smith notes that the patient's overall health contributed to the treatment's chance of success.

"One of the things I feel is relevant to her success is that she's very healthy," Dr. Smith says. "We are working with biologic products. They are only as healthy as the people they come from. I strongly believe that the healthier you are, the more likely these treatments are to succeed."

PRP and BMAC are not yet approved by the Food and Drug Administration (FDA) for use in treating osteoarthritis pain and therefore are typically not covered by insurance. In addition to treating patients with PRP and BMAC, Dr. Smith and colleagues are conducting FDA-approved clinical trials on the use of purified stem cells to treat knee arthritis. And researchers at Mayo Clinic's campus in Jacksonville, Florida, are conducting clinical trials comparing conventional PRP treatment with concentrated bone marrow stem cell injections for osteoarthritis of the knee.

A Study of the Safety and Usability of Culture Expanded STEM Cells Derived from the Patient's Own Fat Tissue for Treatment of Knee Osteoarthritis. Mayo Clinic.

Conventional Platelet-Rich Plasma Versus Concentrated Bone Marrow Stem Cell Injections for Osteoarthritis of the Knee. Mayo Clinic.

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Case study: Use of platelet-rich plasma and bone marrow ...