Lee C. Bollinger and the Revitalization of Columbia’s Medical Center – Columbia University

In his 2002 inaugural address, Columbia President Lee C. Bollinger made it clear that the Universitys medical center would be among his core leadership priorities. The discoveries in the combined areas of medicine and health care, biology, engineering, chemistry, physics, computers, and technologyknown today as the life sciencesare revolutionary in scale, he said. No great university can minimize the potential here for transforming our understanding of life and our capacity to preserve health. And a great university will figure out how to deal with one of the most important questions of higher education, namely how to bridge the intellectual strengths of the health sciences and professions and the fundamental science disciplines in Arts and Sciencesrepresented physically for us by the two campuses of Washington Heights and Morningside Heights.

In his first full year at Columbia, Bollinger took major steps to realize those goals, strengthening the medical centers leadership both within the institution and around the world. He worked with Mailman School Professor Wafaa El-Sadr and then-Dean Allan Rosenfeld on the establishment of ICAP, which went on to become one of the pioneering AIDS/HIV prevention, care, and research initiatives in sub-Saharan Africa. He also created auniversity-wide executive vice president for research, naming David Hirsh, the College of Physicians and Surgeons chair of biochemistry and molecular biophysics, to build an office designed to elevate faculty research though a more systemic, unified, and professionalized system for grant applications, compliance, and administration.While the office supports the academic and clinical research mission across every campus, its work has been especially important at the medical center, which typically generates at least two-thirds of Columbia's total research funding.

While Columbia University Irving Medical Center (CUIMC) had long been among the nations leading academic medical centers, it was essential for the University to address the growing financial and organizational challenges of managing the institutions resources and relationship with its clinical partner, NewYork-Presbyterian Hospital. In the spring of 2006, Bollinger named Lee Goldman of the University of California San Francisco as the executive vice president for health and biomedical sciences and dean of the Faculties of Health Sciences and Medicine. Over the years that followed, the two went on to appoint transformational deans at every CUIMC school: Linda Fried at the Mailman School, Christian Stohler at the College of Dental Medicine, and Bobbie Berkowitz and later Lorraine Frazier at the School of Nursing. Fried, for example, a distinguished geriatrician at Johns Hopkins, expanded Mailmans local and global leadership in establishing auniversity-wide, interdisciplinary aging center to explore and better understand the aging process and its societal implications. After Goldmans retirement in 2020, Bollinger asked Anil Rustgi, professor of medicine, director of the Herbert Irving Comprehensive Cancer Center, and associate dean of oncology at Vagelos College of Physicians and Surgeons, to serve as interim executive vice president and dean of the Faculties of Health Sciences and Medicine during what turned out to be a period of profound challenge and success in CUIMCs response to the COVID-19 pandemic. Last year, Bollinger appointedHarvard Medical School Professor Katrina Armstrong, chair of the Department of Medicine and physician in chief at Massachusetts General Hospital, to write the next chapter of CUIMC history as its chief executive and dean of the Vagelos College of Physicians and Surgeons.

Individually and collectively, these leaders have revitalized the medical center over the last two decades, expanding research, teaching, and clinical care; hiring a diverse range of accomplished faculty members; and deepeningpartnerships with and services for Upper Manhattan communities. They also helped transform the CUIMC campus through a massive investment in acclaimed new buildings for medical education at VP&S and the Nursing School, as well as capital renovations that enhanced some 1.8 million square feet of space for students, clinicians, researchers, and staff. Goldman oversaw the introduction of a modernized Faculty Practice Organization, the opening of a center for outpatient clinical care in Midtown Manhattan, a major expansion of ColumbiaDoctors into New Yorks Westchester County, as well as other locations across the city and region.

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Lee C. Bollinger and the Revitalization of Columbia's Medical Center - Columbia University

Annals of Rheumatic Diseases Publishes Results from Phase 2 Study of emapalumab in Patients with Secondary HLH/Macrophage Activation Syndrome – Yahoo…

Sobi, Inc.

Results showed that MAS remission was seen in 13 of 14 patients with sHLH/MAS receiving emapalumab who had an inadequate response to high-dose glucocorticosteroids

WALTHAM, Mass., April 04, 2023 (GLOBE NEWSWIRE) -- Sobi North America, the North American affiliate of Swedish Orphan Biovitrum AB (Sobi) (STO:SOBI), today announced that the Annals of Rheumatic Diseases has published results from an open-label, single-arm, multicenter phase 2 study evaluating the safety and efficacy of emapalumab, an anti-interferon-gamma monoclonal antibody, being investigated in patients with Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) who developed secondary hemophagocytic lymphohistiocytosis (sHLH)/Macrophage Activation Syndrome (MAS) following an inadequate response to high-dose glucocorticosteroids.

In the published study, 14 patients with sJIA or AOSD and sHLH/MAS who did not respond to high-dose glucocorticosteroids received emapalumab. MAS remission was seen in 13 of the 14 patients by week 8, at a median time of 25 days, based on clinical and laboratory criteria. All 14 patients completed the trial, entered long-term follow-up and were alive at the end of follow-up. Based on the results of this study, Sobi decided to continue to evaluate emapalumab in this patient population and initiated the EMERALD phase 3 study, which is ongoing.

"I believe that the results of this study represent an important milestone for the identification of a potential novel targeted treatment for patients with sJIA or AOSD with sHLH/MAS who have failed high-dose glucocorticoids," said Dr. Fabrizio De Benedetti, Head of the Division of Pediatric Rheumatology and Head of the Laboratory of ImmunoRheumatology at Bambino Ges Children's Hospital in Rome, Italy. "We are eager to collect more data so that emapalumab becomes part of the therapeutic armamentariumfor this rare disease and its high unmet medical need."

sHLH/MAS is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on a background of rheumatologic diseases such as sJIA. It is classified as a secondary form of HLH and is caused by excessive activation and expansion of T cells and macrophages. A body of scientific evidence has been accumulated suggesting interferon gamma (IFN) is a major driver of hyperinflammation in diseases such as sHLH/MAS.

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The results published in the Annals of Rheumatic Diseases are encouraging for patients with sJIA or AOSD developing sHLH/MAS, who have had an inadequate response to high dose glucocorticoid treatment, said Dr. Alexei Grom, Research Director, Division of Rheumatology and Professor of Pediatrics at Cincinnati Children's Hospital Medical Center, in Cincinnati, Ohio. The ability of emapalumab to achieve MAS remission is meaningful as there is a high unmet need for these patients.

We are pleased that this newly published clinical data shows the potential benefit of emapalumab in patients with secondary HLH, said Tony Hoos, Head of Research & Development and Medical Affairs, Chief Medical Officer at Sobi. We remain committed to evaluating emapalumab as a potential new treatment option for patients affected by this severe condition. If our ongoing EMERALD phase 3 study in sHLH/MAS confirms the benefit, we are intending to file a supplemental Biologics License Application.

Emapalumab is marketed in the United States as Gamifant and is indicated for the treatment of adult and pediatric (newborn and older) patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy.Gamifant has not been reviewed or approved by the U.S. Food and Drug Administration for sHLH/MAS.

ContactsFor details on how to contact the Sobi Investor Relations Team, please click here. For Sobi Media contacts, click here.

About macrophage activation syndrome (MAS) Macrophage activation syndrome (MAS) is a severe complication of rheumatic diseases, most frequently systemic juvenile idiopathic arthritis (sJIA) a rare systemic disorder of auto-inflammatory nature with common clinical manifestations such as daily spiking fever, typical transient cutaneous rash, arthritis, lymphadenopathy, hepatosplenomegaly and serositis. MAS is characterized by fever, hepatosplenomegaly, liver dysfunction, cytopenias, coagulation abnormalities and hyperferritinaemia, possibly progressing to multiple organ failure and death. MAS is classified as a secondary form of haemophagocytic lymphohistiocytosis (HLH).

About emapalumab-lzsgEmapalumab-lzsg is a fully human, anti-IFN monoclonal antibody that binds free and receptor-bound IFN, neutralizing its biological activity. In the US, emapalumab-lzsg is indicated for pediatric (newborn and older) and adult primary hemophagocytic lymphohistiocytosis (HLH) patients with refractory, recurrent or progressive disease, or intolerance to conventional HLH therapy. Emapalumab-lzsg is the first and only medicine approved in the US for primary HLH, a rare syndrome of hyperinflammation that usually occurs within the first year of life and can rapidly become fatal unless diagnosed and treated. The FDA approval in 2018 was based on data from the phase 2/3 studies (NCT01818492 and NCT02069899). Emapalumab is indicated for administration through intravenous infusion over one hour twice per week until hematopoietic stem cell transplantation (HSCT). The efficacy and safety of emapalumab are currently being evaluated in a phase 3 study in patients with MAS in Stills disease or systemic lupus erythematosus (SLE) (EMERALD; NCT05001737).

U.S. Indication for Gamifant (emapalumab-lzsg)Gamifant (emapalumab-lzsg) is an interferon gamma (IFN)blocking antibody indicated for the treatment of adult and pediatric (newborn and older) patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy.

Important Safety InformationInfectionsBefore initiating Gamifant, patients should be evaluated for infection, including latent tuberculosis (TB). Prophylaxis for TB should be administered to patients who are at risk for TB or known to have a positive purified protein derivative (PPD) test result or positive IFN release assay. During Gamifant treatment, patients should be monitored for TB, adenovirus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) every 2 weeks and as clinically indicated. Patients should be administered prophylaxis for herpes zoster, Pneumocystis jirovecii, and fungal infections prior to Gamifant administration.

Increased Risk of Infection with Use of Live VaccinesDo not administer live or live attenuated vaccines to patients receiving Gamifant and for at least 4 weeks after the last dose of Gamifant. The safety of immunization with live vaccines during or following Gamifant therapy has not been studied.

Infusion-Related ReactionsInfusion-related reactions, including drug eruption, pyrexia, rash, erythema, and hyperhidrosis, were reported with Gamifant treatment in 27% of patients. In one-third of these patients, the infusion-related reaction occurred during the first infusion.

Adverse ReactionsIn the pivotal trial, the most commonly reported adverse reactions (10%) for Gamifant included infection (56%), hypertension (41%), infusion-related reactions (27%), pyrexia (24%), hypokalemia (15%), constipation (15%), rash (12%), abdominal pain (12%), CMV infection (12%), diarrhea (12%), lymphocytosis (12%), cough (12%), irritability (12%), tachycardia (12%), and tachypnea (12%). Additional selected adverse reactions (all grades) that were reported in less than 10% of patients treated with Gamifant included vomiting, acute kidney injury, asthenia, bradycardia, dyspnea, gastrointestinal hemorrhage, epistaxis, and peripheral edema.

Please see full US prescribing information for Gamifant.

Sobi North AmericaAs the North American affiliate of international biopharmaceutical company Sobi, the Sobi North America team is committed to Sobis vision of providing access to innovative treatments that make a significant difference in the lives of individuals with rare diseases. Our product portfolio includes multiple approved treatments focused on immunology, hematology and specialty care. With U.S. headquarters in the Boston area, Canadian headquarters in the Toronto area, and field sales, medical and market access representatives spanning North America, our growing team has a proven track record of commercial excellence. More information is available atwww.sobi-northamerica.comor atwww.sobi.com.

SobiSobi is a specialized international biopharmaceutical company transforming the lives of people with rare and debilitating diseases. Providing reliable access to innovative medicines in the areas of hematology, immunology and specialty care, Sobi has approximately 1,600 employees across Europe, North America, the Middle East, Asia and Australia. In 2022, revenue amounted to SEK 18.8 billion. Sobis share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi atsobi.com, LinkedIn and YouTube.

Media Contact:matt.tooth@sobi.com

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Annals of Rheumatic Diseases Publishes Results from Phase 2 Study of emapalumab in Patients with Secondary HLH/Macrophage Activation Syndrome - Yahoo...

Five health tech startups you should know – University of Wisconsin-Madison

Health-care startups with their roots at UWMadison have boosted the Wisconsin economy and helped improve patients lives. Photo: Bryce Richter

When it comes to helping Wisconsin residents and the states economy, youCant Stop a Badger. This March, see how UWMadison scientists conduct cutting-edge research that delivers tangible benefits for Wisconsinites and the world. Follow along using #CantStopABadger on social media.Your supportcan help us continue this work.

Five innovative University of WisconsinMadison startups are leveraging scientific research to provide new insights into medicine and treatments, which improves peoples lives and boosts Wisconsins economy.

Starting a research-based company is hard work and it can take years to get established. Here at UWMadison theres increasing support to help innovators on their journey from concept to commercialization, says Discovery to Product (D2P) director Andy Richards. These five startups combined their passion and persistence with D2P and other campus resources to further their ideas to benefit society.

As these early-stage companies continue to grow, theyre creating high-paying scientific and professional jobs in Wisconsin. Theyre also contributing to the states economy by attracting venture capital investment and other funding.

From new methods for drug development to personalizing tumor treatment, here are five startups changing how we experience healthcare:

The idea for Ayrflo was born out of the lab of co-founder Guelay Bilen-Rosas in the UWMadison Department of Anesthesiology. The team is developing a new way of monitoring breathing patterns in patients who are breathing spontaneously recovering from surgery or receiving ongoing sedation, both of which make them vulnerable for respiratory complications. This respiratory monitoring deviceprovides real-time breathing metricsby measuring airflow velocities across the windpipe, immediately detecting changes in breathing. Typical fingertip reading methods can have a devastating lag timein warning about the downstream onset of oxygen deprivation. Real-time monitoring provides critical extra time for medical professionals to address problems and save lives.

Founders: Guelay Bilen-Rosas, Irene Ong, Humberto RosasYear: 2020

UWMadison Connection: School of Medicine and Public Health

The AIQSolutions medical device software platform is built on technology invented at UWMadison by faculty at the Carbone Cancer Center, and the School of Medicine and Public Healths Oncology and Medical Physics departments. The company helps doctors better understand and predict a patients response to treatment for complex diseases such as cancer. The technology usesadvanced algorithms,includingartificial intelligenceto analyze radiology images to create a detailed map of how each area in the body responds to treatment. Physicians are using AIQs product to improve patient outcomes and decreasehealthcarecosts at hospitals, including UW Health.

Founders: Dona Alberti (COO), Robert Jeraj (CSO), Glenn Liu (CMO), Guy Starbuck (CTO)

Year: 2015

Employees: 28

UWMadison Connection: School of Medicine and Public Health

Su-Chun Zhang UW Health / John Maniaci

BrainXell is based on technology developed in the lab of co-founder Su-Chun Zhang, a professor of neuroscience and neurology at the Waisman Center on the UWMadison campus. The company creates drug discovery and toxicology testing tools using patient-derived or genetically modified stem cells. They provide large-scale production of specialized neural cells to the pharmaceutical and biotechnology industry. Neural cells produced with this same technology are used to treat devastating central nervous system diseases such as Parkinsons and Alzheimers as well as spinal cord injuries, through their subsidiary BrainXell Therapeutics.

Founders: Shouming Du (President & CEO), Su-Chun Zhang (Board member)

Year: 2015

Employees: 26

UWMadison Connection: Waisman Center; School of Medicine and Public Health

Mike Sussman

The core technology for Immuto Scientific was developed by co-founder Michael Sussman, UWMadison biochemistry professor, in collaboration with Leon Shohet, engineering professor emeritus. Other co-founders include former engineering postdocs and grad students Josh Blatz, Daniel Benjamin and Faraz Choudhury, as well as Dr. Sussmans lab scientist Benjamin Minkoff. The company develops solutions that accelerate the drug discovery process by automating complex protein structure analysis for protein therapeuticsa type of drug produced within living cells (such as Herceptin). These drugs are used in the treatment of difficult-to-cure diseases such as cancer. Their Plasma Induced Modification of Biomolecules technology helps companies understand how a drug attaches to its target molecule in the body.

Founders: Daniel Benjamin (CTO), Josh Blatz, Faraz A. Choudhury (President & CEO), Benjamin Minkoff, Leon Shohet, Mike Sussman (CSO)Year: 2018

Employees: 11

UWMadison Connection: College of Engineering; College of Agricultural & Life Sciences

Bryan Bednarz

Voximetry is a spin-off company out of the lab of Bryan Bednarz, associate professor of medical physics at UWMadison, who co-founded the company with two other lab members, Joseph Grudzinski and Paul Wickre. Using high-speed graphics processing, the technology helps deliver personalized radiopharmaceutical therapy (a radioactive drug)a safe, effective and targeted approach to tumor treatment. The software provides detailed information on how the drug circulates and how it interacts with both cancers and healthy tissues. This enables physicians and physicists to tailor treatment to each individual patient.

Founders: Bryan Bednarz (CSO), Joseph Grudzinski (CIO), Paul Wickre (CTO)

Year: 2016

Employees: 12

UWMadison Connection: School of Medicine and Public Health

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Five health tech startups you should know - University of Wisconsin-Madison

Direct Biologics Announces FDA Authorization to Expand Ongoing Phase 3 Clinical Study of ExoFlo to All-Cause Moderate-to-Severe ARDS – Yahoo Finance

Ongoing pivotal Phase 3 EXTINGUISH ARDS trial expands to enroll hospitalized patients with moderate-to-severe ARDS, regardless of underlying etiology

ExoFlo is the first cell or cell-derived therapeutic candidate to be evaluated in a Phase 3 trial for all-cause moderate-to-severe ARDS

AUSTIN, Texas, April 04, 2023--(BUSINESS WIRE)--Direct Biologics, LLC, a late-stage biotechnology company leveraging its regenerative medicine platform using extracellular vesicles (EVs) secreted from bone marrow-derived mesenchymal stem cells to address multiple disease indications, announces that the U.S. Food and Drug Administration (FDA) has authorized the expansion of its pivotal Phase 3 EXTINGUISH ARDS trial to evaluate the safety and efficacy of ExoFlo in the treatment of moderate-to-severe acute respiratory distress syndrome (ARDS) from any underlying etiology.

"ARDS is a respiratory disease characterized by a rapid onset of inflammation and fluid in the lungs with unacceptably high mortality and unsustainable treatment costs," said Mark Adams, Chief Executive Officer of Direct Biologics. "We look forward to the results of our Phase 3 study given the significant survival benefit observed in our Phase 2 trial and the absence of any FDA-approved biologic for the treatment of moderate-to-severe ARDS."

The global multicenter randomized, double-blinded, placebo-controlled pivotal Phase 3 EXTINGUISH ARDS trial (NCT05354141) is designed to evaluate the safety and efficacy of ExoFlo for the treatment of all-cause moderate-to-severe ARDS. The trial is expected to enroll 320 patients ages 18-65. The trial will have two treatment arms with half of the enrolled patients receiving a placebo and half receiving up to three intravenous doses of 15 mL of ExoFlo. All patients in both arms will receive standard of care.

The primary endpoint of 60-day all-cause mortality was selected based on the significant survival benefit observed in the completed randomized Phase 2 clinical trial of ExoFlo. Secondary endpoints include ventilator-free days, oxygen-free days and ICU-free days, along with additional exploratory endpoints. In addition, the trial will evaluate the efficacy of ExoFlo in ARDS subtypes to better understand the disease process. In March 2022, ExoFlo received Regenerative Medicine Advanced Therapy, or RMAT, designation by the FDA, which provides opportunities to expedite ExoFlos clinical development for ARDS.

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"FDA authorization to expand our ongoing Phase 3 clinical trial to all-cause ARDS marks a defining moment for regenerative medicine. ExoFlo, designed to repair lung tissue while being a potent anti-inflammatory and immunomodulatory agent, is the first cell or cell-derived therapeutic candidate to be evaluated in a Phase 3 trial for all-cause moderate-to-severe ARDS. In fact, ExoFlo is one of a small handful of biologics that has demonstrated adequate tolerability and clinical activity to gain allowance by the FDA for Phase 3 evaluation in moderate-to-severe ARDS," said Amy Lightner, M.D., Chief Medical Officer of Direct Biologics.

About ARDS

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by acute and diffuse inflammatory lung injury resulting in increased fluid in the lungs, loss of ability to oxygenate and decreased lung compliance. Currently, 15% of all ICU patients and 23% of all ventilated patients in the United States are ARDS patients, which results in an annual intensive care expenditure exceeding $80 billion. The mortality rate of moderate-to-severe ARDS remains unacceptably high at 50%, despite improved ventilatory strategies such as protective ventilation and prone positioning. After decades of research, there is still no targeted or individualized therapy for the treatment of ARDS in the United States. The standard of care is still centered around optimizing mechanical ventilation and supportive care strategies without known mortality benefit.

About Direct Biologics

Direct Biologics is a late-stage biotechnology company leveraging a regenerative medicine platform which uses extracellular vesicles (EVs) secreted from mesenchymal stem cells to address multiple disease indications. Direct Biologics mission is to be the global leader in regenerative medicine through discovery, innovation, advancement of science, and treatment of patients in a safe and effective manner. Our therapeutic product candidate, ExoFlo, is designed to be a scalable, reproducible, and effective next-generation biologic that leverages our proprietary EV platform technology designed to reduce inflammation, modulate the immune system, and restore tissue through cellular regeneration. Direct Biologics is currently conducting the global Phase 3 EXTINGUISH ARDS clinical trial of ExoFlo for the treatment of hospitalized adults with moderate-to-severe acute respiratory distress syndrome (ARDS). In addition, the Company has initiated Phase 1 clinical trials with ExoFlo for the treatment of ulcerative colitis and Crohns disease, and expanded access trials in solid abdominal organ transplantation and severe ARDS patients. Direct Biologics intends to pursue additional clinical applications including perianal fistulizing Crohns disease and necrotizing enterocolitis. Headquartered in Austin, Texas, Direct Biologics also has an R&D facility at the Center for Novel Therapeutics on the campus of University of California at San Diego, and operations and order-fulfillment center in San Antonio, Texas. For more information, please visit http://www.directbiologics.com and follow us on Twitter @directbiologics.

View source version on businesswire.com: https://www.businesswire.com/news/home/20230404005769/en/

Contacts

Direct Biologics 800-791-1021info@directbiologics.com Twitter: @directbiologics

Investor Relations LHA Investor RelationsYvonne Briggs310-691-7100YBriggs@lhai.com

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Direct Biologics Announces FDA Authorization to Expand Ongoing Phase 3 Clinical Study of ExoFlo to All-Cause Moderate-to-Severe ARDS - Yahoo Finance

Multiple Myeloma in the Black Community – Everyday Health

For many Black Americans with multiple myeloma, socioeconomic status can stand in the way of even standard care, especially for those who live in rural areas, according to Calloway-Campbell.

Youre not close to an academic center, she says. And local doctors may not have even heard of multiple myeloma. Getting to a doctor can be near-impossible for people who dont have a car or other means of transportation, as well, and even gathering information can be challenging without easy access to Wi-Fi.

Treatment for myeloma is exorbitantly expensive too. According to a study published in JAMA Open Network in July 2021, the average lifetime cost of treating multiple myeloma was upwards of $185,000 an intimidating price tag for most people, much less for those who may be unemployed or underpaid, lacking health insurance, or inadequately covered.

The National Cancer Institute (NCI)reports that while 67 percent of white Americans under 65 and 44 percent over 65 have private health insurance, only 51 percent of African Americans under 65 and 28 percent over 65 are insured. And private health insurance is key to quality myeloma care.

According to the NCI, for instance, non-white recipients of Medicaid or Medicare are less likely to be prescribed new drugs or treated with stem cell transplants compared to non-white patients who have private insurance. This is significant, given a quarter of Medicare and Medicare Advantage recipients are African American.

Financial assistance for myeloma treatment is available though. On the IMF websites Financial Assistance page, for instance, are a list of options ranging from small stipends, which can be put directly toward treatment, to sources of help for non-medical expenses, such as transportation and childcare. The organization also has a page with information about drug reimbursement and help with copays.

Other sources for financial aid for people of all ethnicities living with multiple myeloma include:

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Multiple Myeloma in the Black Community - Everyday Health

Diamyd Medical partners with JDRF to advance the DIAGNODE-3 … – PR Newswire

STOCKHOLM, April 4, 2023 /PRNewswire/ -- Diamyd Medical and JDRF, the leading global type 1 diabetes research and advocacy organization, have entered into a four-year research and development collaboration including a non-dilutive $5 million award to Diamyd Medical to support its ongoing Phase 3 trial with the precision medicine antigen-specific immunotherapy Diamyd. The grant will be funded under JDRF's Industry Discovery & Development Partnerships program that focuses on commercialization of therapeutics and devices for the treatment, cure, and prevention of type 1 diabetes and its complications.

"We could not have a better partner than JDRF as we are focusing on rapid advancement of our antigen-specific immunotherapy towards the market," said Ulf Hannelius, CEO of Diamyd Medical. "We expect this collaboration to significantly boost patient recruitment to this international study as well as our commercial preparations."

"JDRF is committed to supporting and advancing disease modifying therapies to delay and reverse type 1 diabetes," said Sanjoy Dutta, Ph.D., chief scientific officer at JDRF. "We are excited about Diamyd Medical's groundbreaking Phase 3 trial and its potential advancements in the preservation of insulin production for people recently diagnosed with type 1 diabetes."

"JDRF has played a crucial role in many of the most novel therapeutics and devices that have been approved in the field for those with type 1 diabetes," said Mark Atkinson, Ph.D., director of the Diabetes Institute at the University of Florida and Diamyd Medical Board Member. "JDRF's commitment to this Phase 3 program is a validation of the scientific and clinical value of the antigen-specific immunotherapy Diamyd. It also emphasizes the importance of making disease modifying therapies available to everyone affected by this disease."

About Diamyd MedicalDiamyd Medical develops precision medicine therapies for Type 1 Diabetes. Diamyd is an antigen-specific immunotherapy for the preservation of endogenous insulin production. DIAGNODE-3, a confirmatory Phase III trial is actively recruting patients with recent-onset Type 1 Diabetes in eight European countries and is being preparedto start recruiting patients in the US this summer. Significant results have previously been shown in a large genetically predefined patient group in a large-scale meta-analysis as well as in the Company's European Phase IIb trial DIAGNODE-2, where the Diamyd was administered directly into a lymph node in children and young adults with recently diagnosed Type 1 Diabetes. A biomanufacturing facility is being set up in Ume for the manufacture of recombinant GAD65, the active ingredient in the antigen-specific immunotherapy Diamyd. Diamyd Medical also develops the GABA-based investigational drug Remygen as a therapy for regeneration of endogenous insulin production and to improve hormonal response to hypoglycaemia. An investigator-initiated Remygen trial in individuals living with Type 1 Diabetes for more than five years is ongoing at Uppsala University Hospital. Diamyd Medical is one of the major shareholders in the stem cell company NextCell Pharma AB as well as in the artificial intelligence company MainlyAI AB.

Diamyd Medical's B-share is traded on Nasdaq First North Growth Market under the ticker DMYD B. FNCA Sweden AB is the Company's Certified Adviser.

About JDRF JDRF's mission is to accelerate life-changing breakthroughs to cure, prevent and treat T1D and its complications. To accomplish this, JDRF has invested more than $2.5 billion in research funding since our inception. We are an organization built on a grassroots model of people connecting in their local communities, collaborating regionally and globally for efficiency and broader fundraising impact, and uniting on a global stage to pool resources, passion, and energy. We collaborate with academic institutions, policymakers, and corporate and industry partners to develop and deliver a pipeline of innovative therapies to people living with T1D. Our staff and volunteers throughout the United States and our five international affiliates are dedicated to advocacy, community engagement, and our vision of a world without T1D. For more information, please visit jdrf.org or follow us on Twitter (@JDRF), Facebook (@myjdrf), and Instagram (@jdrfhq).

About Type 1 Diabetes Type 1 diabetes is an autoimmune condition that causes the pancreas to make very little insulin or none at all. This leads to dependence on insulin therapy and the risk of short or long-term complications, which can include highs and lows in blood sugar; damage to the kidneys, eyes, nerves, and heart; and even death if left untreated. Globally, it impacts nearly 9 million people. Many believe T1D is only diagnosed in childhood and adolescence, but diagnosis in adulthood is common and accounts for nearly 50% of all T1D diagnoses. The onset of T1D has nothing to do with diet or lifestyle. While its causes are not yet entirely understood, scientists believe that both genetic factors and environmental triggers are involved. There is currently no cure for T1D.

For further information, please contact:Ulf Hannelius, President and CEOPhone: +46 736 35 42 41E-mail: [emailprotected]

The following files are available for download:

SOURCE Diamyd Medical AB

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Diamyd Medical partners with JDRF to advance the DIAGNODE-3 ... - PR Newswire

Rejuvenation Roundup March 2023 – Lifespan.io News

March marks the beginning of spring and the time for renewal, and this month, labs around the world have looked into renewing older concepts of aging and discovered potential methods for renewing our bodies.

Partnership Opportunities for the 5th Annual Age-Related Disease Therapeutics Summit: This conference is seeking partners who want to showcase their companies to biotechnology and investment leaders, listing contract research, biomarkers of aging, epigenetics, and preclinical services as the preferred areas of interest.

Thank you to OneSkin, one of our philanthropic partners who has generously agreed to donate a percentage of their monthly revenue to Lifespan.io, to support our mission of longevity biotechnology advocacy and education.

OneSkin is a longevity company developing products designed to extend skin and body health by targeting aging at its source.

Team and activities

Rep. Bilirakis on the Longevity Science Caucus: We in the longevity field have received powerful allies on Capitol Hill with the creation of the bipartisan Congressional Caucus for Longevity Science. We had the opportunity to ask questions of one of its co-chairs.

Lifespan News

Human Brain Organoids in Rats: Emmett Short talks about how human neurons in rat brains can actually fulfill critical functions in these animals.

NAD+, Fat, and Muscle: On this episode, Emmett Short goes over a new study showing that nicotinamide riboside (NR) increases both fat and muscle.

Best Time to Exercise: This episode features some rather surprising results gleaned from examining the effects of regular morning exercise on UK Biobank participants.

Protein and Muscle: This Lifespan News is on a study showing that diets with less protein are connected to better muscle maintenance with aging.

Exercise and Supplements: Emmett Short talks about a recent meta-study of exercise and supplements, which showed inconclusive results despite its large dataset.

Young Blood for Brain Boosting: This episode discusses a study showing that the brains of old mice benefit by receiving the blood of young mice.

Prof. Tzipi Strauss on the Upcoming Longevity Center: In Sheba Medical Center in Israel, the first-of-its-kind Longevity Center will soon open its doors. We spoke with its future director, Prof. Tzipi Strauss, who is also leading the Department of Neonatology at Sheba.

Prof. George Church on Cellular Reprogramming and Longevity: Professor of Genetics at Harvard Medical School, a veteran geroscientist, and a serial entrepreneur, George Church hardly needs an introduction. While we are always happy to discuss the present and future of geroscience with him, this interview focuses on the two gene therapy papers that he recently co-authored.

Ashley Zehnder on Harnessing Animal Genes Against Aging: Many species have developed amazing mechanisms to cope with various drivers of aging. A handful of bold entrepreneurs are trying to go commercial, and one of them is Ashley Zehnder, DVM, PhD, co-founder and CEO of Fauna Bio, a biotech startup that looks for protective genotypes in animals in order to weaponize them against human diseases.

Ryan OShea of Future Grind hosts this months podcast, showcasing the events and research discussed here.

Human Fasting Modulates Macrophage Function: This month, Dr. Oliver Medvedik explored a recent study that looked at the effects of prolonged fasting on human macrophages and how metabolites from that fasting increased median lifespan in Caenorhabditis elegans.

Insider Insight: Meet the Organizers of LongHack: LongHack, the longevity hackathon hosted by DeSci organization VitaDAO, was held on January 20th-23rd, 2023. Gathering researchers, developers, and other interested parties to create new tools and solutions for longevity, ten teams competed to impress the judging panel and take home prizes.

A Lasting Rise in Investment in the Longevity Sector: 2021 marked one of the biggest years in longevity financing, with 2022 following closely behind. Over the past ten years, the industry has grown in financing from $500 million in 2013 to a peak of $6.2 billion in 2021.

Dr. Nir Barzilai on How to Age Later: In Age Later: Healthspan, Lifespan, and the New Science of Longevity, Dr. Nir Barzilai provides an insightful and comprehensive overview of the latest research on aging and longevity.

Research Roundup

Association Between BMI and Mortality Revisited: Ryan K. Masters, professor at CU Boulder, suggests that when adjusted for body shape and lifelong shifts, the relationship between BMI and mortality is more linear and robust than previously thought, with normal BMI being the healthiest.

Exercise and Supplements Against Age-Related Inflammation: In a new systematic review, researchers have shown that combining some dietary supplements and exercise might be beneficial for people over the age of 60.

How NAD+ Relates to Smell Loss with Age: Researchers publishing in Aging Cell have elucidated a relationship between aging, the loss of smell, and NAD+ in a mouse model. Roughly half of people over the age of 65 experience a decreased ability to smell, and research has shown that it is an early biomarker for neurodegenerative diseases.

Extracellular Vesicles as a Hallmark of Aging: A review paper published in Cells has described multiple ways in which the secretion of extracellular vesicles changes with aging, leading the authors to propose it as its own hallmark.

New Small Molecule Alleviates Alzheimers in Mouse Model: Scientists have developed a custom-made molecule that targets a post-translationally modified kinase linked to Alzheimers, improving symptoms in a murine model of the disease.

Metformin and Rapamycin Rejuvenate Stem Cells in Mice: In a new study published in Aging Cell, researchers have shown that two promising anti-aging agents, the antibiotic rapamycin and the anti-diabetic drug metformin, reverse aging in a population of intestinal stem cells.

Young Blood Alters Gene Expression in Old Brain Cells: Research published in Nature Aging has shown that heterochronic parabiosis, the circulatory joining of young and old organisms, has rejuvenative effects on the gene expression of multiple types of brain cells in mice.

New Treatment Alleviates Depression Symptoms in Mice: Scientists have shown that the protein GDF11 can reverse depression-like symptoms in naturally aged mice and in a mouse model of depression.

Mitochondria, DNA, and Oxidative Stress: A paper published in Experimental Gerontology has provided a fresh and detailed look at the effects of oxidative stress on longevity. The free radical theory of aging, which purports that reactive oxygen species (ROS) are the core driver of aging, was developed all the way back in 1956.

Epigenetic Biomarker for Measuring Aging Through Fitness: A new biomarker for measuring biological aging based on physical fitness has been published in Aging, and it has been found to be useful in predicting health issues.

Excessive Fat, Not Sugar, Leads to Obesity in Mice: In a new study published in Endocrinology and Metabolism, researchers have shown that fat rather than sugar is the macronutrient that drives obesity and other detrimental metabolic changes if it constitutes a large proportion of dietary calories.

Inflammation Strongly Predicts Mortality After Statin Use: Analyzing data from three clinical trials, scientists have shown that excessive inflammation is a much stronger predictor of cardiovascular and all-cause mortality in patients on statins than excessive LDL cholesterol levels.

Sleep Apnea and Inflammatory Biomarkers of Tooth Decay: A study published in Heliyon has explained a relationship between sleep apnea and an increase of inflammatory factors in the mouth that are connected to the gum disease peridontitis.

The Human Cost of Metabolic Diseases: A new paper published in Cell Metabolism has shown the growing influence of metabolic diseases in an aging population. Metabolic diseases include hypertension, type 2 diabetes, hyperlipidemia, obesity, and non-alcoholic fatty liver disease.

Mediterranean Diet Might Lower Risk of Dementia: In a large-scale observational study, British scientists have shown that high levels of adherence to the Mediterranean diet might substantially lower the risk of dementia. The Mediterranean diet, is based on ingredients such as olive oil, vegetables, legumes, fish, and whole grains.

Vital Muscle Enzyme Declines With Aging: Research published in Nature Metabolism has described PCYT2, an enzyme essential for muscle function, and how it declines with aging. A necessary lipid synthesizer in muscle Human beings need PCYT2 as part of the Kennedy pathway to synthesize two critical components of the phosopholipid membrane that surrounds cells.

Long-Term Resistance Exercise Increases Autophagy: In a new systemic review published in Autophagy Reports, researchers have demonstrated that exercise plays a role in regulating autophagy, depending on its type. Autophagy is the way cells break down misbehaving or nonfunctional organelles and proteins in the cell.

Promoting Muscle Regeneration With an Immune Factor: A paper published today in Nature Aging has shown that a macrophage-regulating factor has a significant impact on muscle regeneration.

Vesicles from Senescent Cells Encourage Young Stem Cells: Scientists have shown that extracellular vesicles derived from senescent stem cells can improve the proliferation, viability, and migration capacity of healthy stem cells.

Senescent Cells and Loose Teeth: A team of researchers has recently published a study on the effects of senescence on periodontal tissues, which hold teeth to bone, in Aging.

Inhibiting DREAM for Enhanced DNA Damage Repair: In a new study published in Nature Structural and Molecular Biology, researchers have demonstrated that by manipulating the DREAM protein complex, a major regulator of DNA damage response, it might be possible to alter the number of DNA mutations accumulated with age.

Using AI to Measure Age Through the Eyes: An accepted manuscript in eLife Sciences has described eyeAge, a new clock that uses deep learning to analyze the eye in detail in order to predict chronological age and age acceleration.

Daily Step Count, Less Mortality, Diminishing Returns: A new study using wearable accelerometers suggests that you dont have to clock extreme numbers of steps every day to stay healthy.

Associations of sleeping, sedentary and physical activity with phenotypic age acceleration: Sedentary behavior was positively associated with aging. Replacing sedentary behaviors with walking/bicycling or moderate to vigorous physical activity was adversely associated with aging among adults.

Coenzyme Q10 supplementation improves the motor function of middle-aged mice by restoring the neuronal activity of the motor cortex: This study shows that CoQ10 improves brain mitochondrial function and physical performance in mice.

Increased SIRT1 Concentration Following Four Years of Selenium and Q10 Intervention Associated with Reduced Cardiovascular Mortality at 10-Year Follow-Up: This study suggests that this combination increases SIRT1 in a way that helps to prevent vascular aging.

Dietary magnesium intake is related to larger brain volumes and lower white matter lesions with notable sex differences: Higher dietary magnesium intake has been found to be associated with better brain health in the general population, particularly women.

Potential reversal of biological age in women following an 8-week methylation-supportive diet and lifestyle program: There was a statistically significant (p=.039) difference in the participants mean biological age before (55.83 years) and after (51.23 years) the 8-week diet and lifestyle intervention, with an average decrease of 4.60 years.

Six-Month Synbio Administration Affects Nutritional and Inflammatory Parameters of Older Adults: The PROBIOSENIOR project demonstrated how SYNBIO supplementation may positively influence some nutritional and inflammatory parameters in the elderly.

Mendelian randomization analyses reveal causal relationships between the human microbiome and longevity: These findings strongly implicate that these commensal microbes play a role in human longevity and suggest that they should be monitored to promote longevity.

AAV1.NT-3 gene therapy prevents age-related sarcopenia: The researchers reported functional, in vivo muscle physiology improvements

Transcriptional activation of endogenous Oct4 via the CRISPR/dCas9 activator ameliorates Hutchinson-Gilford progeria syndrome in mice: These results suggest that partial rejuvenation by activating this Yamanaka factor can be used as a novel strategy in treating geriatric diseases.

Ageing as a software design flaw: Well-known aging researcher Joo Pedro de Magalhes expands on the idea that aging is the result of misguided genetic programming rather than entropic damage.

Necroptosis inhibition counteracts neurodegeneration, memory decline, and key hallmarks of aging, promoting brain rejuvenation: These results demonstrate that necroptosis, which mediates degeneration of injured axons, contributes to age-dependent brain degeneration.

Effect of peripheral cellular senescence on brain aging and cognitive decline: Preserved cognition was associated with the removal of peripheral senescent cells, which decreased the systemic inflammation that normally drives neuroinflammation, BBB breakdown, and impaired synaptic function.

Immunotherapeutic approach to reduce senescent cells and alleviate senescence-associated secretory phenotype in mice: These results show that HCW9218 represents a novel immunotherapeutic approach and a clinically promising new class of senotherapeutic agents targeting cellular senescence-associated diseases.

The Fifth Annual Age-Related Disease Therapeutics Summit: The Age-Related Disease Therapeutics Summit will once again be held in San Francisco this year, and Lifespan.io readers are encouraged to use the code 32026Lifespan when signing up.

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Rejuvenation Roundup March 2023 - Lifespan.io News

Comprehensive proteomics and platform validation of urinary … – BMC Medicine

Research over the past several years has uncovered potentially important urine biomarkers and tests for BC, including BTA and NMP22. BTA-stat, an FDA-approved urine biomarker, is used clinically to detect bladder tumor-associated antigen (human complement factor H-related protein) in the urine. A meta-analysis of BTA stat reported a specificity of 67% and a sensitivity of 75% after reviewing 13 studies [8]. The sensitivity levels of BTA-stat have been shown to positively correlate with increasing grade of BC [8]. However, BTA-stat has several limitations. These include lower specificity values and issues relating to false-positive results in benign conditions [6]. Hence, urine BTA-stat may have limitations in the diagnosis and monitoring of disease progression. Similarly, NNP22 is an FDA-approved urine biomarker designed to detect the NMP22 protein levels which are high due to cell turnover from tumor apoptosis. A meta-analysis of 19 studies has identified this marker to have a pooled specificity of 88% and a sensitivity of 56% [7].

As opposed to studies looking at an isolated protein in the urine, a few screens have been reported where multiple proteins were examined simultaneously. Summarized below are a couple of studies documenting biomarkers with both sensitivity and specificity values greater than or equal to 85%. Goodison et al. performed a validation study for the urinary concentrations of 14 proteins (A1AT, APOE, ANG, CA9, CCL18, CD44, IL-8, MMP-9, MMP-10, OPN, PAI-1, PTX3, SDC1, and VEGF) using an ELISA [30]. An 8-biomarker panel (ANG, APOE, CA-9, IL-8, MMP-9, MMP-10, PAI-1, and VEGF) achieved the most accurate BC diagnosis with a sensitivity of 92% and a specificity of 97%. However, a panel of 3 biomarkers (APOE, IL-8, and VEGF) also performed well with a sensitivity of 90% and a specificity of 97% for the detection of BC [30]. Kumar et al. identified a 5-biomarker panel consisting of Apolipoprotein A4, Coronin-1A, DJ-1/PARK7, Gamma synuclein, and Semenogelin-2. ELISA and western blot data obtained an AUC of 0.92 and 0.98, respectively, in diagnosing Ta/T1 BC (sensitivity 79.2% and 93.9% for ELISA; specificity 100% and 96.7% for western blot) [31]. For the diagnosis of T2/T3 BC, the panel of markers achieved an AUC of 0.94 and 1, respectively, using the same methods (sensitivity 86.4% and 100%; specificity 100%) [31].

Low-grade BC has a high recurrence rate; therefore, identifying biomarkers for the surveillance of BC is essential for the potential clinical management of the disease. Rosser et al. identified 10 biomarkers (ANG, APOE, CA9, IL-8, MMP-9, MMP-10, SDC1, SERPINA1, SERPINE1, and VEFGA) using ELISA for monitoring urine for recurrent BC. The complete panel achieved an AUC of 0.90, a sensitivity of 79%, and a specificity of 88% [32]. De Paoli et al. identified a panel of 6 biomarkers (cadherin-1, EN2, ErbB2, IL-6, IL-8, and VEGF-A) and three clinical parameters including BCG therapies, stage at the time of diagnosis, and past recurrences. The panel achieved an AUC of 0.91 and was identified through microarray and ELISA analysis [33].

There are several reasons to discriminate patients with bladder cancer from benign conditions. In patients with hematuria, it would be helpful to identify who needs cystoscopic evaluation which is invasive. Given that urine proteins are easily measurable and are compatible with point-of-care monitoring, a quick urine test could dramatically impact triage and workflow in urology outpatient clinics. Likewise, in bladder cancer surveillance, a reliable urine biomarker can help determine if cancer (like CIS) was missed or to avoid cystoscopy in marker-negative patients. Similarly, urine biomarkers that can reliably distinguish MIBC from NMIBC can inform us as to who has the more aggressive disease. When used as a routine point-of-care test (either at home or at outpatient visits), these urinary biomarkers may facilitate earlier identification of aggressive disease and design of tailored therapy.

The present work represents the first attempt to screen>1000 urine proteins for urine biomarker candidates in BC, using a relatively novel aptamer-based screen. Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 being key regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression (Fig.3D). This study has also uncovered urine proteins that outperform current FDA-approved markers in many respects. Several urine proteins (d-dimer, Apolipoprotein A1, MMP-1, Properdin, Calgranulin B) significantly discriminate BC from UC with AUC values from 0.85 to 0.96 (p-value<0.0001). As a single biomarker, urine d-dimer was able to discriminate BC from UC with 96% accuracy (sensitivity=95%; specificity=90%). Likewise, several urine proteins (IL-8, IgA, Fibronectin, C2, Proteinase 3) significantly discriminate MIBC from NMIBC with AUC 0.840.99 (p-value<0.001). Interestingly, several of the proteins described above have been documented to be elevated in bladder cancer tissue (at the RNA or protein level) and/or implicated in tumor biology at some level, as summarized in Additional file 1: Table S5. Considering their biomarker potential and functional properties based on the literature (Additional file 1: Table S5), these urine proteins warrant further investigation, including, d-dimer [34], Apolipoprotein A1 [35, 36], Apolipoprotein L1, Calgranulin B [37, 38], complement C2 [39], Fibronectin [40,41,42,43], Ficolin-3, IL-8 [44,45,46,47,48,49], IgA [50], MMP-1 [51, 52], Properdin, and Proteinase 3 [53]. A summary of previous research on these proteins can be found in Additional file 1: Table S6. Additional markers increased in tissues are described in Additional file 1: Table S7.d-dimer is a specific cleavage product of fibrin and a symbol of hyperfibrinolysis [34]. It is the primary diagnostic tool in various diseases, such as deep venous thrombosis, systemic illness, and cancers [54]. Previous studies have reported that molecules in the coagulation/fibrinolysis system, especially plasma fibrinogen and d-dimer, are abnormal in cancer patients [34]. In the present study, urine d-dimer levels show a significant ability to differentiate BC from UC (AUC=0.96) (p<0.0001). After correcting for patient demographics, urine d-dimer is still eligible for inclusion within the 5-biomarker panel for best distinguishing BC from UC. Perhaps most impressive is the observation that urine d-dimer demonstrates a high sensitivity for the detection of BC (95%), and at a fixed specificity of 0.8, it can achieve a sensitivity of 0.97. Hence, as a single biomarker, urine d-dimer outperforms current FDA-approved biomarkers and competing biomarkers in the research literature as a sensitive biomarker for BC detection.

Apolipoproteins (Apolipoprotein A1 and Apolipoprotein L1) are proteins known to interact with the lipids of the lipoprotein core and also the aqueous environment of the plasma. Apolipoprotein A1 is the primary protein component of high-density lipoprotein while Apolipoprotein L1 is a minor component. Previous studies have validated Apolipoprotein A1 as a novel urinary biomarker for BC [35, 36]. In the current research, Apolipoprotein A1 was the second-best performing protein in terms of the AUC value (0.91) in distinguishing BC from UC.

After adjusting for demographics, this protein ranked within a 5-marker panel for distinguishing BC from UC. Similarly, Apolipoprotein L1 also ranked within the 5-marker panel for distinguishing BC from UC and MIBC from NMIBC.

Calgranulin B (S100A9) is a zinc- and calcium-binding protein that plays a prominent role in regulating inflammatory and immune responses. Several S100 proteins, including S100A9, have received attention regarding their possible role in tumor development and progression and studies report an increased expression in a variety of tumors, including ovarian, colon, gastric, and prostate cancer [37]. Increased expression of S100A9 protein in the serum has been previously associated with tumor grade [37]. Current validation results of Calgranulin B are promising as it was among the top markers in discriminating BC from UC with an AUC of 0.85.

Complement proteins may promote tumor growth in the context of chronic inflammation [39]. Complement C2s relation to BC at this time is unknown. However, the present study identified this protein as the fourth best single protein for differentiating MIBC from the NMIBC stage. Properdin is also a member of the complement system, controlling the alternate pathway of complement activation. Research on properdin in BC is limited. However, in the current study, properdin demonstrated the third highest AUC value (AUC=0.89, p<0.0001) in discriminating BC from UC. These biomarker findings are consistent with the observation that changes in complement activation constitute one of the major pathways that predict BC disease progression, based on STEM analysis (Fig.3D).

Fibronectin is a glycoprotein component of the extracellular matrix. Tumor cells can attach to fibronectin via integrins or other cell surface receptors [55]. Its effectiveness as a urine biomarker for BC has been explored in a variety of studies [40,41,42,43]. Here, fibronectin showed the third best discriminatory ability in identifying MIBC compared to NMIBC. The marker exhibited an AUC value of 0.87 (p<0.0001).

IL-8 is a proinflammatory CXC chemokine. It has previously been associated with the promotion of neutrophil chemotaxis and degranulation [56]. Increased expression of IL-8 has been associated with endothelial cells, infiltrating neutrophils, tumor-associated macrophages, and cancer cells [56]. Therefore, IL-8 may be a significant regulatory factor within the tumor microenvironment. Previous studies have identified urinary IL-8 as a potential marker for BC [44,45,46,47,48,49]. In the present study, urine IL-8 was the best-performing protein in the MIBC vs NMIBC comparison, with an AUC of 0.99 (p<0.0001), although its specificity was modest at a fixed sensitivity of 80%. Taken together with a wealth of supporting literature, this marker has the potential to be a monitoring tool for BC disease progression and warrants further analysis in this context.

IgA is an immunoglobulin and is often the first line of defense in the resistance against infections, particularly in mucosal tissues. A correlation of intra-tumor IgA1 and poor overall survival in BC patients has been identified in a previous study [50]. However, research regarding IgA in BC urine is limited. The data presented in this study indicated that urinary IgA may differentiate MIBC from NMIBC (AUC=0.89, p<0.0001). Overall, IgA performed 2nd best out of a total of 30 urinary markers validated for this comparison. Of particular note, urine IgA exhibited the highest specificity of 80% for MIBC, at 80% sensitivity, out-performing IL-8.

Matrix metalloproteinases (MMP) are a group of zinc-dependent proteolytic enzymes. Their role involves remodeling of the extracellular matrix. Many studies have evaluated the levels of MMPs in cancer patients and have reported the vital roles of some MMPs as potential diagnostic and prognostic biomarkers in tumorigenesis [57]. The current study has uncovered MMP-1 as the fourth best-performing molecule for distinguishing BC from UC (AUC=0.89, p<0.0001). This protein was also included in a 5-marker panel for distinguishing BC from UC. At the mechanistic level, one can envision tissue matrix remodeling as an important pre-requisite for cancer progression.

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Comprehensive proteomics and platform validation of urinary ... - BMC Medicine

What makes blood stem cells transform? Regulation of RNA splicing … – Science Daily

Researchers at Lund University Faculty of Medicine have determined a novel mechanism linking the metabolism of ribonucleic acids, RNA, to the development of leukemia in myelodysplastic syndrome patients, MDS. In a study published in the Molecular Cell journal, they explain what makes hematopoietic stem cells acquire malignant traits in cancer.

RNA splicing is a major nexus of gene expression regulation, shaping cellular identity during development, frequently altered in human cancers. This process is mediated by a complex molecular machinery known as the spliceosome, which enables the production of multiple and functionally distinct proteins from single genes.

A team of researchers led by Dr. Cristian Bellodi recently discovered a hardwired genetic control mechanism modulating individual spliceosomal components, known as splicing factors, in cells harboring oncogenic lesions common in human cancers.

This work highlighted core splicing proteins, including SF3B1, frequently mutated in various cancers. Splicing factor mutations are particularly prevalent in MDS, a group of heterogeneous hematological disorders characterized by defective blood stem cells and a high risk of leukemia development. "Accumulating evidence is highlighting a role for aberrant splicing in cancer even in the absence of splicing factors mutations. However, little is known about the contribution of the non-mutated splicing factors in tumor evolution," explain the researchers.

The team began by investigating how the levels of non-mutated SF3B1, a core spliceosome component, contribute to the MDS disease. With Prof. Eva Hellstrm-Lindberg's group at the Karolinska Institute, Maciej Ciela and coworkers discovered dynamic regulation of SF3B1 levels during the malignant transformation from MDS to leukemia.

"Strikingly, we found that SF3B1 protein accumulates in MDS patients to ensure genome integrity via splicing regulation. Blocking this mechanism drastically accelerates progression to aggressive leukemia," remarks Maciej Ciela, a postdoctoral fellow in the RNA and Stem Cell Biology group at tLund University Stem Cell Center and first author of the study. Now, a group leader at IMOL, Poland.

The authors further investigated the molecular determinants controlling the SF3B1 production during the transition to leukemia. These studies led to the breakthrough discovery that SF3B1 synthesis depends on a single RNA chemical modification mark, known as N6-methyladenosine, m6A, deposited on its messenger RNA.

"We found that the presence of m6A RNA modification provides a "stop signal" that regulates SF3B1 production, a critical event that impacts accumulation of DNA damage in leukemic cells," explains Maciej Ciela.

"Our results revealing a new critical connection between RNA metabolism and genome integrity in leukemic stem cells, provide important insights into the complex underlying mechanisms fueling cancer development in MDS patients. Our findings are particularly timely, as increasing evidence indicates that RNA modification and splicing alterations represent new therapeutic vulnerabilities for treating hematological and solid cancer patients," concludes Cristian Bellodi, Associate Professor, Division of Molecular Hematology and Lund Stem Cell Center, Lund University.

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What makes blood stem cells transform? Regulation of RNA splicing ... - Science Daily

UCLA-led study uses base editing to correct mutation that causes … – UCLA Newsroom

Key takeaways

A new UCLA-led study suggests that advanced genome editing technology could be used as a one-time treatment for the rare and deadly genetic disease CD3 delta severe combined immunodeficiency.

The condition, also known as CD3 delta SCID, is caused by a mutation in the CD3D gene, which prevents the production of the CD3 delta protein that is needed for the normal development of T cells from blood stem cells.

Without T cells, babies born with CD3 delta SCID are unable to fight off infections and, if untreated, often die within the first two years of life. Currently, bone marrow transplant is the only available treatment, but the procedure carries significant risks.

In a study published in Cell, the researchers showed that a new genome editing technique called base editing can correct the mutation that causes CD3 delta SCID in blood stem cells and restore their ability to produce T cells.

The potential therapy is the result of a collaboration between the laboratories of Dr. Donald Kohn and Dr. Gay Crooks, both members of the Eli and Edythe Broad Center ofRegenerative Medicine and Stem Cell Research at UCLA and senior authors of the study.

UCLA Broad Stem Cell Research Center

Dr. Donald Kohn and Dr. Gay Crooks

Kohns lab has previously developed successful gene therapies for several immune system deficiencies, including other forms of SCID. He and his colleagues turned their attention to CD3 delta SCID at the request of Dr. Nicola Wright, a pediatric hematologist and immunologist at the Alberta Childrens Hospital Research Institute in Canada, who reached out in search of a better treatment option for her patients.

CD3 delta SCID is prevalent in the Mennonite community that migrates between Canada and Mexico. Because newborns are not screened for SCID in Mexico, I often see babies who have been diagnosed late and are returning to Canada quite sick, Wright said.

When Kohn presented Wrights request to his lab, Grace McAuley, then a research associate who joined the lab at the end of her senior year at UCLA, stepped up with a daring idea.

Grace proposed we try base editing, a very new technology my lab had never attempted before, said Kohn, a distinguished professor of microbiology, immunology and molecular genetics, and of pediatrics.

Base editing is an ultraprecise form of genome editing that enables scientists to correct single-letter mutations in DNA. DNA is made up of four chemical bases that are referred to as A, T, C and G; those bases pair together to form the rungs in DNAs double-helix ladder structure.

While other gene editing platforms, like CRISPR-Cas9, cut both strands of the chromosome to make changes to DNA, base editing chemically changes one DNA base letter into another an A to a G, for example leaving the chromosome intact.

I had a very steep learning curve in the beginning, when base editing just wasnt working, said McAuley, who is now pursuing an M.D.-Ph.D. at UC San Diego and is the studys co-first author. But I kept pushing forward. My goal was help get this therapy to the clinic as fast as was safely possible.

McAuley reached out to the Broad Institutes David Liu,the inventor of base editing, for advice on how to evaluate the techniques safety for thisparticular use. Eventually, McAuley identified a base editor that was highly efficient at correcting the disease-causing genetic mutation.

UCLA Broad Stem Cell Research Center

Dr. Gloria Yiu and Grace McAuley

Because the disease is extremely rare, obtaining patient stem cells for the UCLA study was a significant challenge. The project got a boost when Wright provided the researchers with blood stem cells donated by a CD3 delta SCID patient who was undergoing a bone marrow transplant.

The base editor corrected an average of almost 71% of the patients stem cells across three laboratory experiments.

Next, McAuley worked with Dr. Gloria Yiu, a UCLA clinical instructor in rheumatology, to test whether the corrected cells could give rise to T cells. Yiu used artificial thymic organoids,which are stem cell-derived tissue models developed by Crooks lab that mimic the environment of the human thymus the organ where blood stem cells become T cells.

When the corrected blood stem cells were introduced into the artificial thymic organoids, they produced fully functional and mature T cells.

Because the artificial thymic organoid supports the development of mature T cells so efficiently, it was the ideal system to show that base editing of patients stem cells could fix the defect seen in this disease, said Yiu, who is also a co-first author of the study.

As a final step, McAuley studied the longevity of the corrected stem cells by transplanting them into a mouse. The corrected cells remained four months after transplant, indicating that base editing had corrected the mutation in true, self-renewing blood stem cells. The findings suggest that corrected blood stem cells could persist long-term and produce the T cells patients would need to live healthy lives.

This project was a beautiful picture of team science, with clinical need and scientific expertise aligned, said Crooks, a professor of pathology and laboratory medicine. Every team member played a vital role in making this work successful.

The research team is now working with Wright on how to bring the new approach to a clinical trial for infants with CD3 delta SCID from Canada, Mexico and the U.S.

This research was funded by theJeffrey Modell Foundation, the National Institutes of Health, the Bill and Melinda Gates Foundation, the Howard Hughes Medical Institute, the V Foundation and the A.P. GianniniFoundation.

The therapeutic approach described in this article has been used in preclinical tests only and has not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans. The technique is covered by a patent application filed by the UCLA Technology Development Group on behalf of the Regents of the University of California, with Kohn and McAuley listed as co-inventors.

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UCLA-led study uses base editing to correct mutation that causes ... - UCLA Newsroom