New hydrogel stem cell treatment repairs injured brain tissue in mice – Science Daily

A new 'hybrid' hydrogel, which allows clinicians to safely deliver stem cells to the site of a brain injury in mice, has been developed by researchers from the University of Melbourne and the Australian National University.

A hydrogel is a water-based gel that can be used to deliver substances into the body and can be used to promote the effective growth of new cells.

Published in Nature Communications, the proof-of-concept breakthrough solves a major challenge faced by stem cell researchers since the 1980s -- keeping stem cells alive for long enough to allow them to evolve into the cells required to create new tissue when they are inserted into a damaged part of the body.

The hydrogel supplies both the stem cells and oxygen needed to keep stem cells alive during the injection process and to ensure the stem cells evolve into the type of cells needed to create new tissue to repair damage. Researchers believe this advance will benefit stem cell treatments in many other parts of the body beyond the brain and central nervous system.

The team that developed the hydrogel is co-led by University of Melbourne Professor David Nisbet, Director of The Graeme Clark Institute for Biomedical Engineering; and The Australian National University (ANU) Professor Colin Jackson, a member of both the Innovations in Peptide and Protein Science, and Synthetic Biology Australian Research Council Centres of Excellence.

Professor Nisbet said: "After an injury such as a stroke, there is a dead area in the brain, including the blood system. So, we need a temporary blood supply to support cells until the blood system repairs. This patented hydrogel provides that.

"Very few drug treatments can treat conditions like stroke or Parkinson's Disease and they have little efficacy. There are currently no treatments that can reverse these conditions."

Professor Jackson said the breakthrough will interest researchers and clinicians globally and is likely to lead to many revolutionary medical treatments.

"Proof of concept has now been demonstrated within the brain of mice, but the research represents a generalisable strategy for developing injectable nanomaterials for a diverse range of applications, including cell transplantation, gene and drug delivery, 3D in vitro disease models and organ-on-a-chip technology," Professor Jackson said.

Over five years of research, the team discovered that a synthetic protein based on myoglobin -- a natural protein found in high concentrations in the heart muscles of sperm whales and horses -- added to their hydrogel provided the sustained oxygen release needed to ensure stem cells survive the delivery process and develop into the type of cells needed to repair brain tissue.

Whales and other deep-diving animals are thought to have evolved high concentrations of myoglobin in their muscle tissue so they could slowly absorb as much oxygen as possible while diving. Similarly, horses are thought to have evolved higher concentrations of myoglobin so they could run over longer distances.

University of Melbourne Professor Clare Parish conducted the mouse studies and said the results were achieved in injured brain tissue, raising the possibility for growing new tissue for future human treatment.

"We saw that the hydrogel incorporating myoglobin and stem cells repaired injured brain tissue. Analysis at 28 days after delivery of the hydrogel revealed significantly enhanced survival and growth of the new stem cells that are needed for healthy brain functioning, compared with a hydrogel without myoglobin," Professor Parish said.

"We observed that the new tissue could be stimulated in a similar way to healthy brain tissue, providing the first evidence of the benefits of including oxygen delivery within a hydrogel to achieve the long-term survival and integration of stem cell transplants."

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New hydrogel stem cell treatment repairs injured brain tissue in mice - Science Daily

Stem cell therapies promise breakthrough in Dubai life sciences – The National

A new stem cell research laboratory due to open in Dubai promises to accelerate the understanding of human genomics in the region and improve health outcomes from genetic diseases.

The Hortman Stem Cell Laboratory is due to open in May on The Palm Jumeirahs Golden Mile, with laboratories and clean rooms purpose-built for stem cell isolation, culture and expansion to take the next step in preventive health care and research in Dubai.

As the UAE becomes a regional hub for life sciences, the first stem cell congress held in Dubai heard about the value of banking cord blood and placental tissue in preserving human health.

Stem cell research is an emerging area of healthcare, allowing parents to store cord blood from the placenta of newborns which could be used to treat cancers, immune deficiencies and genetic disorders.

Hearing the words you have cancer were the scariest words ever said to me

Linda Konsinski

Although average stem cell therapy is expensive typically costing from $5,000 to $50,000 the results can be life saving.

We will begin clinical trials at the lab once it opens in May to take stem cells from cord tissue to primarily research heart and lung diseases, said Dr Fatma Alhashimi, director of the Hortman Stem Cell Laboratory.

Dr Fatma AlHashimi, director of Hortman Stem Cell Laboratory in Dubai, speaks at the first stem cell congress in Dubai. Hortman Stem Cell Laboratory

The challenges we are facing in the UAE is having enough GMP [good manufacturing practices] labs for this kind of research and clinical trials.

It is expensive and not always cost-effective but it saves lives and that is where the value is.

The centre will also research metabolic disorders, sickle cell anaemia and Thalassemia, an inherited blood condition that is one of the most common genetic disorders in the UAE.

Longevity science and the value of gene therapies in treating long-term disease and illness were discussed by specialists at the congress, while patient case studies revealed the value of therapies.

Linda Konsinski, a mother of three from the US, was diagnosed with leukaemia 15 years ago, at age 38.

A cord blood transplant from a two-year-old boy saved her life after a blood test revealed a dangerously high white blood cell count that indicated Philadelphia Chromosome positive acute lymphocytic leukaemia.

Hearing the words you have cancer were the scariest words ever said to me, said Ms Konsinski.

The day I heard them my life turned upside down.

My doctors said I needed a bone-marrow transplant to survive long-term but neither of my sisters were a match so I had to search registries around the world.

Unable to find a match, a cord blood transplant was considered instead.

Doctors at the City of Hope Medical Centre in California offered to help and a search began.

As cord blood was already in storage and any mismatches were more tolerated than bone marrow transplants, two potential donors were found.

Cord blood from a baby boy in New Jersey stored for 10 years and another from a young boy in Italy stored for six years were found to be suitable.

Ms Konsinski flew to California to begin the transplant process, staying for about 17 weeks for treatment and recovery.

Each day got better and the cells began to graft, she said.

When I went home, it was the best day ever. I have been given more time with my family and been able to see so many things I thought I would never get to see.

Other developments discussed at the congress included gene replacement therapies for spinal muscular atrophy, a condition that affects about 1 in 10,000 newborns.

It is the second most common fatal autosomal recessive disorder after cystic fibrosis, with 60 per cent of those with Type 1 SMA experiencing rapid, irreversible motor neuron loss.

Gene therapy has helped reverse symptoms, allowing children to sit up, feed, swallow and walk with assistance.

We know that children who are treated pre-symptomatically generally do better, so there is a need for neonatal screening, said Dr Vivek Mundada, speaking at the congress as a consultant paediatric neurologist at the Medcare Women and Children Hospital, Dubai.

Many countries are moving towards that, with Kuwait and Qatar having already started in the Middle East as have Belgium, Germany and Poland.

If you treat and diagnose these children early, you can make a huge difference to their lives.

Updated: March 02, 2023, 5:00 AM

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Stem cell therapies promise breakthrough in Dubai life sciences - The National

Targeting glioblastoma with a cancer-killing virus – City of Hope

Glioblastoma is a virtually incurable brain cancer with a five-year-survival rate of only 10%.Its heartbreaking to keep telling people in clinic that we dont have a cure, said Jana Portnow, M.D., co-director of City of Hopes Brain Tumor Program. This is a tough tumor, and these patients havent benefited

from the major advances weve seen over the last 20 years to treat other cancers. Theres no effective targeted agent or immunotherapy for glioblastoma. We need to find better treatments.

Portnow and her team just received a $12 million grant from the California Institute for Regenerative Medicine (CIRM) to perform a Phase 1 clinical trial to assess an exciting new combination treatment strategy against glioblastoma.

These very invasive tumors lack clear boundaries, and most chemotherapies cannot adequately reach diffuse tumor cells in the brain. In order to overcome these treatment obstacles, this trial for patients with recurrent high-grade glioma is evaluating the strategy of packaging an oncolytic virus (a virus that can kill cancer cells without harming normal brain tissue) within tumor-homing neural stem cells. The team expects this approach will not only more effectively distribute the oncolytic virus to tumor tissue, it will protect the oncolytic virus from being destroyed by the patients immune system while making its way to tumor cells.

Karen Aboody, M.D., whose City of Hope translational research lab pioneered neural stem cell-delivered cancer therapies, collaborating with Maciej Lesniak, M.D., and David Curiel, Ph.D., on development of the trial virus product, explained how it works.

We engineered tumor-targeting neural stem cells to produce an adenovirus, which is a cold virus, but it only replicates in cells that have a high expression of a protein called survivin. Since only the cancer cells express high levels of survivin, it doesnt harm the normal tissue surrounding the tumor, she said. Just the way a cold virus infects your cells, this virus infects tumor cells and keeps replicating until it kills them by bursting them open. This virus can be especially effective on tumors that have become resistant to radiation and chemotherapy.

When the tumor cell bursts open, it releases more cancer-killing virus that spreads to neighboring tumor cells, effectively amplifying its tumor-killing effect until normal tissue is reached, and the virus ceases to further replicate. Additionally, this process of bursting open the tumor cells also exposes new tumor proteins to the immune system, potentially stimulating a secondary immune response against the tumor.

Another difficulty in treating brain tumors is that they are heterogenous, meaning they are made up of different cells resulting from various mutations in different parts of the tumor, so therapies that target only specific genetic mutations are ineffective. But the oncolytic virus is able to target all malignant cells.

However, treating cancer with a virus has its own obstacle to overcome the patients immune system, which can neutralize the virus before it can reach cancer cells. The trick was finding a way for the virus to hide from the immune system.

Enter the neural stem cell.

To avoid attack by the immune system, the virus is delivered inside a neural stem cell that is tumor-tropic, meaning it seeks out tumors and invades the cancer cells.

A major obstacle to successfully treating glioblastoma is that these tumor cells multiply so quickly and are so invasive that, even before the main tumor mass can be removed, malignant cells have already invaded other parts of the brain. The ability of the neural stem cells to migrate through normal brain tissue to seek out distant cancer cells and deliver the oncolytic virus may be the key to improving the efficacy of oncolytic viruses for treating brain tumors.

The neural stem cell serves as kind of a Trojan horse, Aboody said. The virus is concealed by the stem cell, which protects it from being neutralized by the immune system, allowing it to reach the tumor and efficiently infect the tumor cells.

'This virus can be especially effective on tumors that have become resistant to radiation and chemotherapy.'Karen Aboody, M.D.

Neural stem cells are naturally drawn to pathology in the brain, as Aboody demonstrated in a seminal study, published in PNAS in 2000. They are attracted to inflammation and chemokines secreted by the tumor cells. In fact, the more aggressive and invasive the tumor, the more stem cells are attracted to it.

In another study, published in Lancet Oncology in 2021, Aboody and her colleagues at Northwestern University showed that delivering a single dose of virus-loaded neural stem cells directly into the brain of newly diagnosed glioma patients was safe and feasible. This next CIRM-funded study will assess the safety and initial efficacy of treating participants with multiple weekly doses of this therapy,

Working with City of Hopes Center for Biomedicine & Genetics, Aboodys lab has engineered a line of virus-producing neural stem cells and banked billions of them as an off-the-shelf cancer treatment ready for clinical use.

If this Phase 1 study is successful, further manufacturing and clinical development will be supported by Calidi Biotherapeutics, a biotechnology company with which City of Hope has partnered to develop stem cell-based platforms for delivering oncolytic viruses.

Intravenous treatment for brain cancer is limited by the blood brain barrier, a kind of gatekeeper that keeps harmful substances in the blood from entering the central nervous system.

One way to bypass the blood brain barrier is to deliver the treatment directly into the brain. For this multiple treatment study, instead of making participants undergo surgery each time a dose needs to be given, a temporary catheter will be implanted into the surgical cavity after the main tumor is removed. Then the catheter, which is attached to a reservoir placed under the scalp, will be used to administer serial weekly doses of the virus-producing neural stem cells in the outpatient setting.

To reach patients across the United States, three other brain tumor centers are participating in this study. In addition to City of Hope, the clinical trial will be conducted at Northwestern University, Stanford University and Wake Forest University, all of which are National Cancer Institute-designated comprehensive cancer centers, and all of which serve diverse patient populations.

People who are at least 18 years old and have recurrent high-grade gliomas, such as glioblastoma or grade 3 astrocytomas, may be eligible to participate in this clinical trial.

For more information, contact City of Hope at 866-405-1663 and ask to speak to someone in the Brain Tumor Program or email neurosurgerymail@coh.org.

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Targeting glioblastoma with a cancer-killing virus - City of Hope

Discussing Current and Potential Expansions to the Lymphoma … – Targeted Oncology

The treatment landscape for patients with lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL), has undergone significant changes with the advent of chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies. However, challenges and questions remain in this space.

According toMatthew Matasar, MD, one of the major highlights for this patient population includes the newer FDA-approved treatment option of mosunetuzumab (Lunsumio). Mosunetuzumab was approved in December 2022 for patients with relapsed/refractory follicular lymphoma based on findings from the pivotal phase 2 GO29781 study (NCT02500407).1

In follicular lymphoma, clearly, we are coming upon the era of bispecific antibodies, with mosunetuzumab and competitive molecules that are being developed in this space as well. We're likely to find ourselves in a situation where we have multiple options in the treatment of [patients with] follicular lymphoma with bispecific antibodies, said Matasar, chief of the division of blood disorders at the Rutgers Cancer Institute and professor at the Rutgers Robert Wood Johnson Medical School, in an interview with Targeted OncologyTM.

In the interview, Matasar breaks down recent data for patients with non-Hodgkins lymphoma and what new studies mean for this patient population now, and in the future.

Targeted Oncology: What is a top highlight for the field of follicular lymphoma?

Matasar: For follicular lymphoma, we have important updates on the activity and durability of responses with the treatment with mosunetuzumab. Mosunetuzumab is a novel bispecific antibody targeting CD20 and CD3, creating an immune synapse with healthy T cells. This has been described in prior [meetings] and publications and clearly is an active medicine in patients with multimodal follicular lymphoma, with overall response rates [ORR] of 80% and complete response [CR] rates of 60%.

The important question, however, is how durable are these responses? We now have maturing data, with a median follow-up now of 27 months. We see that the median duration of response, CR, and even median progression-free survival [PFS] have not yet been reached, which for me, emphasizes the point that not only is this agent highly active in relapsed FL, but the responses are quite durable. We need further follow-up and certainly we have a lot more to learn.

What about for patients with non-Hodgkins lymphoma?

In the area of non-Hodgkins lymphoma aggressive B-cell lymphoma, I presented work that we conducted with colleagues at the Dana Farber and City of Hope. Looking at improving treatments [in the] second line [for patients with] large cell lymphoma that are eligible for stem cell transplant. We know that even in this era of CAR-T cell therapy there are a subset of patients who should receive and benefit from platinum-based chemoimmunotherapy with planned autologous transplant in consolidation. [This is for those] with later relapsing large cell lymphoma those who ever relapse greater than 12 months beyond completion of first-line therapy. That being said, the standard of care treatment have a sub optimal ORR to CR rate and we clearly need to do better for such patients.

What new data is there for this patient population?

We presented our phase 2 study called Pola-R-ICE [NCT04833114], which incorporates the use of polatuzumab vedotion [and RICE [rituximab [Rituxan], ifosfamide, carboplatin and etoposide]], the antibody drug conjugate targeting CD79B, in combination with RICE for patients with relapsed large cell lymphoma who were eligible for subsequent consolidated stem cell transplant.2 Briefly, in the study patients received 2 or 3 cycles of the Pola-R-ICE treatment and those who had chemo-sensitive disease went on to receive a standard of care auto transplant, and then after transplant would receive polutuzumab monotherapy to complete a total of 6 doses. So, 3 doses if they got 3 cycles beforehand and 4 if they only required 2.

We showed high activity for this combination in this patient population despite a high-risk patient population putting many patients that currently would be shunted towards the CAR-T program, because of primary refractory or early relapsing disease. We nonetheless showed high ORR and CR rates and the ability to get patients to transplant. The data are still maturing, and we're looking to see what the impact of the consolidative treatment is going to look like in terms of durability of response, but very encouraging results that we were able to present.

What are your hopes for the future of treatment for patients with lymphoma?

In follicular lymphoma, clearly, we are coming upon the era of bispecific antibodies, with mosunetuzumab and competitive molecules that are being developed in this space as well. We're likely to find ourselves in a situation where we have multiple options in the treatment of [patients with] follicular lymphoma with bispecific antibodies. Important questions will remain, however, including both the durability of these agents as well as the optimal sequencing and which patients should be getting CAR T-cell therapy, which patients be getting bispecific antibodies, and how do these agents work in sequence? And how can we optimize the course of care for a patient navigating through follicular lymphoma?

In DLBCL, there's clearly still a lot of work to be done in clarifying the optimal second line treatment program for patients who should be receiving the stem cell transplant, as well as further innovation that's required in terms of novel ways of assessing response. [Other questions remain such as] should we be incorporating [minimal residual disease] decision making into the transplant decision making apparatus? And how can we best incorporate other novel therapies into multi agent programs, again, with the intention of improving outcomes for our patients with highest risk disease.

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Discussing Current and Potential Expansions to the Lymphoma ... - Targeted Oncology

Jakubowiak Highlights PFS Benefit Seen With KRd Maintenance in … – OncLive

Welcome to OncLive On Air! Im your host today, Ashling Wahner.

OncLive On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In todays episode, we had the pleasure of speaking with Andrzej Jakubowiak, MD, PhD, a professor of medicine and director of the Myeloma Program at the University of Chicago in Illinois. Dr Jakubowiak joined us to discuss interim findings from the phase 3 ATLAS trial (NCT02659293), which investigated lenalidomide (Revlimid) plus carfilzomib (Kyprolis) and dexamethasone (KRd) vs lenalidomide maintenance in patients with newly diagnosed multiple myeloma who had previously received induction therapy and autologous stem cell transplant.

At a median follow-up of 33.8 months, patients who received KRd had a median progression-free survival (PFS) of 59.1 months vs 41.4 months in those who received lenalidomide alone. This translated to a 49% reduction in the risk of progression or death in the KRd arm. Additionally, the ATLAS investigators found a correlation between high minimal residual disease negativity and improved PFS in the KRd arm.

In our exclusive interview, Dr Jakubowiak contextualized the ATLAS findings within the broader post-transplant multiple myeloma treatment landscape, shared pertinent interim data from the trial, and previewed the next steps for this research.

___

Thats all we have for today! Thank you for listening to this episode of OncLive On Air. Check back on Mondays and Thursdays for exclusive interviews with leading experts in the oncology field.

For more updates in oncology, be sure to visit http://www.OncLive.com and sign up for our e-newsletters.

OncLive is also on social media. On Twitter, follow us at @OncLive and @OncLiveSOSS. On Facebook, like us at OncLive and OncLive State of the Science Summit and follow our OncLive page on LinkedIn.

If you liked todays episode of OncLive On Air, please consider subscribing to our podcast on Apple Podcasts, Spotify, Google Podcasts, Amazon Music, and many of your other favorite podcast platforms,* so you get a notification every time a new episode is posted. While you are there, please take a moment to rate us!

Thanks again for listening to OncLive On Air.

*OncLive On Air is available on: Apple Podcasts, Google Podcasts, Spotify, Amazon Music, Audacy, CastBox, Deezer, iHeart, JioSaavn, Listen Notes, Player FM, Podcast Addict, Podchaser, RadioPublic, and TuneIn.

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Jakubowiak Highlights PFS Benefit Seen With KRd Maintenance in ... - OncLive

Stay Healthy Champ: Fans Send Well-Wishes as 37-Year-Old … – EssentiallySports

WWE is one of the most popular wrestling promotions in the entire world. It is widely known for being one of the biggest, and a place every budding pro wrestler wants to work for. The company has created a different aura for itself and is also known for providing one of the safest environments.

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However, even after following major safety rules and precautions, WWE often witnesses their superstars falling victim to injuries. Last year, it was Cody Rhodes who suffered a pectoral injury, and now recently another major WWE Superstar updated his fans on social media about his injury.

Former NXT Champion, and friend/foe of Johnny Gargano, recently took to his Instagram profile and gave an insight to his fans about his injury. Tommaso Ciampa updated his fans on his injury status, and also his recovery process.

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He wrote in detail about the treatment he would undergo and made it transparent with his fans. Ciampa arrived in Medellin, Colombia, to undergo a stem-cell treatment. He praised the city and the decorations all over. He further also wrote how he has undergone 7 MRIs. And how he has an upcoming orientation for his stem-cell recovery.

Fans were heartbroken to hear about the condition their favorite superstar is in. And soon they started reacting to it.

As soon as Ciampa updated on his Instagram profile about his treatment, his fans swarmed on the post and let their well-wishes known to the former NXT Champion. His post was soon filled with well-wishes about his recovery from the fans.

Read More: 285 Lb WWE Monster, Who Destroyed Brock Lesnar in 85 Seconds, Had an Intense Backstage Faceoff With Dwayne Johnson

Here are some of the top comments:

Hell yeah

Cant wait to see your journey back man

Hope to see you back asap

Love you, Blackheart. Youre an inspiration always

Good look with your up coming treatment

DIY coming soon

You dude. Youre awesome. I knew you were recovering from hip surgery but the stem cell stuff sounds kind of scary. I hope youre not sick on top of your injury.

Hope your better really soon

we need you back please stay healthy champ and pat yourself on the back.

Wishing you the best Ciampa. Return to the ring better than before

Ciampa underwent a surgery last year to recover from his hip issue. The Blackheart has been on the receiving end of several injuries ever since his NXT days, and fans currently hope that he does not suffer anymore.

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Fans might be disheartened to hear about Ciampas condition. And it is not soon that they will witness Ciampa coming back to WWE. After undergoing a hip surgery last year, he has been out of action. And now with the stem cell treatment coming up, he would not be back till late 2023.

Former WWE Champion Big E has also been out of action since last year, after suffering a neck injury. WWE fans are now awaiting both Big E and Ciampas return. Both of these stars connect well with the fans, and they cannot wait more to witness them come back.

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Watch This Story: Dwayne Johnsons Daughter Simone to The Undertakers Daughter Kaia Meet Daughters of Top WWE Stars

When do you guys think Big E and Ciampa will be in good shape to return?

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Stay Healthy Champ: Fans Send Well-Wishes as 37-Year-Old ... - EssentiallySports

Vertex to develop conditioning agent for SCD gene editing therapy… – Sickle Cell Disease News

Vertex Pharmaceuticals will use ImmunoGen technology to develop less aggressive conditioning approaches for exagamglogene autotemcel (exa-cel), its experimental gene editing therapy for sickle cell disease (SCD) and transfusion-dependent beta thalassemia.

Vertex will pay ImmunoGen $15 million up front to use its antibody-drug conjugate (ADC) technology to develop gentler and more targeted conditioning agents.

Chemotherapy, a type of conditioning agent, is used to wipe out a persons faulty cells before gene editing therapy is used. Its known to be aggressive and poorly tolerated, though.

While Vertex will be able to obtain worldwide exclusive rights to develop and commercialize any products developed during an initial research phase, ImmunoGen may be entitled to up to $337 million, based on certain development and commercial milestones. If any product is approved, it will also earn royalties.

We look forward to evaluating the potential of ImmunoGens technology to develop a gentler conditioning regimen for use with Vertexs exagamglogene autotemcel (exa-cel), for the potential treatment of sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT), Mike Cooke, PhD, senior vice president of Vertex Cell and Genetic Therapies, said in a company press release.

Vertex and its development partner, CRISPR Therapeutics, have opened a rolling submission with the U.S. Food and Drug Administration (FDA) for exa-cels approval in the U.S. That application is expected to be complete this year.

The treatment holds fast track, regenerative medicine advanced therapy (RMAT), and orphan drug designations in the U.S., all of which offer regulatory support and financial incentives for its development.

Regulatory submissions have also been made in the U.K. and EU, where the treatment holds orphan drug status. It also holds a priority medicines designation in the E.U.

A feature of SCD is the production of a faulty version of hemoglobin, the protein in red blood cells responsible for oxygen transport. Beta thalassemia patients have low hemoglobin or lack it altogether. Patients have anemia, wherein there isnt enough healthy red blood cells to carry oxygen through the body.

Formerly known as CTX001, exa-cel involves genetically modifying a patients hematopoietic stem cells (blood cell precursors) to make high levels of fetal hemoglobin, aversion of the protein produced during fetal development that switches to an adult version after birth. Fetal hemoglobin is more effective than its adult counterpart at carrying oxygen.

Edited stem cells are transplanted back into the patient via a stem cell transplant, where theyre expected to populate blood with cells that produce high levels of fetal hemoglobin, which can ease anemia.

In clinical trials, patients have been treated with the chemotherapy agent busulfan before receiving the edited cells, but busulfan is aggressive and often poorly tolerated.

ImmunoGen has been working on ADCs to offer a more targeted approach for cancer patients. ADCs are made by attaching a potent cancer-killing agent to an antibody that will specifically recognize cancer cells. This approach is expected to help improve treatment tolerability because only cancer cells are targeted.

Vertex will use that technology to develop targeted conditioning agents for SCD and beta-thalassemia patients undergoing exa-cel treatment.

Given Vertexs extensive experience discovering and developing transformative medicines for patients with serious diseases, we are thrilled they have chosen to explore ImmunoGens technology to develop ADCs for transplant conditioning in connection with gene editing, said Michael Vasconcelles, MD, ImmunoGens executive vice president of research, development, and medical affairs.

Data from an ongoing open-label Phase 2/3 clinical trial called CLIMB121 (NCT03745287) showed a single dose of exa-cel boosted fetal hemoglobin and prevented painful vaso-occlusive crises in patients with severe SCD, ages 12-35.

Reported side effects were consistent with those known to be associated with busulfan.

A pair of open-label Phase 3 trials CLIMB151 (NCT05329649)andCLIMB141 (NCT05356195) are evaluating the safety and effectiveness of exa-cel in pediatric patients, ages 2-11, with severe SCD or beta-thalassemia. CLIMB-151 is recruiting at sites in the U.S. and Italy. CLIMB-141 is recruitingin Canada, Germany, and the U.K.

Participants in any of these trials can enroll in CLIMB-131 (NCT04208529), where the treatments safety and effectiveness will be monitored for up to 15 years.

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Vertex to develop conditioning agent for SCD gene editing therapy... - Sickle Cell Disease News

Possible treatment strategy identified for bone marrow failure … – Washington University School of Medicine in St. Louis

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Researchers working with pharma collaborations to develop better treatments

A new study from Washington University School of Medicine in St. Louis identifies a possible treatment strategy for some bone marrow failure syndromes. Shown are human embryonic stem cells engineered to have a mutation that causes poikiloderma with neutropenia, a bone marrow failure syndrome that increases a patient's risk of developing dangerous infections.

Bone marrow is the spongy tissue inside bone responsible for making red blood cells, white blood cells and platelets. Bone marrow failure syndromes lead to an increased risk of developing dangerous infections, anemia and an increased risk of blood cancers.

Research led by Washington University School of Medicine in St. Louis has identified a possible treatment strategy for a rare bone marrow failure syndrome that is named poikiloderma with neutropenia. The work also may have implications for treating other bone marrow failure syndromes with similar underlying dysfunctions.

The research is published March 3 in the journal Science.

Poikiloderma with neutropenia is caused by mutations in a gene called USB1. Despite knowing the genetic error that causes the disease, the specifics of what the error does to cause bone marrow failure have long been a mystery. When the bone marrow fails, the body cant make healthy red blood cells, white blood cells and platelets. People with these types of diseases are at increased risk of infections and are prone to developing skin and blood cancers.

There are no cures for poikiloderma with neutropenia, said co-senior author Luis Batista, PhD, an associate professor of medicine. Patients are at high risk of dying from complications of infections, and scientists had no idea why mutations in this gene lead to bone marrow failure. In this new study, we found a novel role for an enzyme that opens the door to future clinical trials. There are investigational drugs that block this enzyme, so we are hopeful that clinicians who treat these patients may find this a promising strategy to pursue.

Studying human embryonic stem cells engineered to model this syndrome, the investigators, including co-senior author Roy Parker, PhD, of the University of Colorado, Boulder, found a problem with the processing of molecules called microRNA. The processing problem causes specific microRNA molecules to break down faster than they should. Without sufficient levels of these microRNAs, the stem cells cant develop into normal blood cells.

Our study shows that normal USB1 is cutting off the long tails of these microRNAs, which stabilizes their structure, giving them time to do their jobs forming blood products, said first author Hochang Jeong, PhD, a postdoctoral research associate in Batistas lab. When USB1 is mutated in this disease, these microRNA tails are much longer than they should be. We know that having longer tails makes microRNAs and other classes of RNA molecules more easily targeted for degradation. What we learned is there should be an equilibrium between the enzyme that puts the tails on and the enzyme that chops off the tails.

While there is not yet a known way to restore the ability to properly remove the tails, investigational drugs already exist that block the enzymes responsible for putting the tails on. Blocking this enzyme in this disease potentially could restore the equilibrium between the adding and subtracting of tails.

The enzymes responsible for adding the tails are called PAPD5 and PAPD7, and inhibitors of these enzymes have been investigated in human clinical trials for other diseases, including hepatitis B. For this study, the researchers used a PAPD5 inhibitor called RG7834. Preventing the addition of the long tail stabilized the structure of the microRNAs, increasing their levels and restoring normal blood cell formation by these stem cells. The researchers are working with industry partners to develop new PAPD5 and PAPD7 inhibitors that are specifically designed to treat this and similar conditions.

We are working with different companies to develop better and more specific PAPD5 inhibitors to treat this rare syndrome, Batista said. In my lab, we are big advocates for the study of rare diseases. Combined, rare diseases are not rare at all, and these patients deserve our attention. PAPD5 inhibition is poised to be a potential treatment for other bone marrow failure syndromes.

This research was supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH), grant number 1R01HL137793-01; the Howard Hughes Medical Institute; the Department of Defense; the American Cancer Society; Siteman Cancer Center at Washington University School of Medicine in St. Louis; the Center for Regenerative Medicine at Washington University School of Medicine in St. Louis; and the National Research Foundation of Korea, grant number NRF-2021R1A6A3A03045808.

Co-senior authors Batista and Parker and two of their co-authors are inventors on a provisional patent filed by the University of Colorado, Boulder, that covers Usb1 as a target in leukemia.

Jeong H, Shukla S, Fok WC, Huynh TN, Batista LFZ, Parker R. USB1 is a miRNA deadenylase that regulates hematopoietic development. Science. March 3, 2023.

About Washington University School of Medicine

WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,800 faculty. Its National Institutes of Health (NIH) research funding portfolio is the third largest among U.S. medical schools, has grown 52% in the last six years, and, together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,800 faculty physicians practicing at 65 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Childrens hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.

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Possible treatment strategy identified for bone marrow failure ... - Washington University School of Medicine in St. Louis

FDA Grants Orphan Drug Designation to Temferon for Treatment of … – BioSpace

MILAN and NEW YORK, March 02, 2023 (GLOBE NEWSWIRE) -- Genenta Science (NASDAQ: GNTA), a clinical-stage immuno-oncology company developing a cell-based platform harnessing the power of hematopoietic stem cells to provide durable and safe treatments for solid tumors, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Temferon for the treatment of glioblastoma multiforme (GBM).

"We expect that the FDAs decision to grant Orphan Drug Designation to Temferon will enhance the development of our cell therapy, which we believe has the potential to address the unmet medical need of patients and strengthen our clinical program," said Pierluigi Paracchi, Chief Executive Officer of Genenta. "The Orphan Drug Designation program highlights the significant need for an efficacious therapy for patients suffering from glioblastoma multiforme."

Temferon is a proprietary cell therapy designed to reprogram the tumor microenvironment by delivering immunomodulatory molecules directly to tumors. Genenta is testing Temferon in an ongoing Phase 1/2a clinical trial in newly diagnosed patients with GBM who have an unmethylated MGMT gene promoter (uMGMT-GBM).

GBM is the most common malignant primary brain tumor and the most aggressive diffuse glioma, with unmethylated MGMT promoter status identified in approximately 60% of the GBM population.

The ODD program supports the development of treatments that address diseases affecting fewer than 200,000 people in the United States (which equates to approximately 6 cases per 10,000 population). Incentives that come with the designation include eligibility for federal grants, tax credits for qualified clinical trials, prescription drug user fee exemptions, and a seven-year marketing exclusivity period upon FDA approval.

About Genenta Science Genenta (www.genenta.com) is a clinical-stage biotechnology company engaged in the development of a proprietary hematopoietic stem cell gene therapy for the treatment of a variety of solid tumor cancers. Temferon is based on ex-vivo gene transfer into autologous Tie2+ hematopoietic stem/progenitor cells (HSPCs) to deliver immunomodulatory molecules directly via tumor-infiltrating monocytes/macrophages (Tie2 Expressing Monocytes - TEMs). Temferon, which is under investigation in a phase 1/2a clinical trial in newly diagnosed Glioblastoma Multiforme patients who have an unmethylated MGMT gene promoter (uMGMT-GBM), is designed to reach solid tumors, induce a durable immune response not restricted to pre-selected tumor antigens nor type, and avoid systemic toxicity, which are some of the main unresolved challenges in immuno-oncology.

Forward-Looking StatementsStatements in this press release contain forward-looking statements, within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as anticipate, believe, contemplate, could, estimate, expect, intend, seek, may, might, plan, potential, predict, project, suggest, target, aim, should, "will, would, or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on Genentas current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict, including risks related to the completion and timing of the phase 1/2a clinical trial or any studies relating to the treatment of glioblastoma multiforme patients who have an unmethylated MGMT gene promoter (uMGMT-GBM). Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully in the section titled Risk Factors in the Annual Report on Form 20-F for the year ended December 31, 2021, filed with the Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Genenta Science S.p.A. undertakes no duty to update such information except as required under applicable law.

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FDA Grants Orphan Drug Designation to Temferon for Treatment of ... - BioSpace

BioRestorative Therapies Receives Notice of Allowance by the … – GlobeNewswire

--Notice of allowance will be the third US patent to issue from this ThermoStem family targeting obesity and metabolic disorders, including type 2 diabetes--

MELVILLE, N.Y., March 02, 2023 (GLOBE NEWSWIRE) -- BioRestorative Therapies, Inc. (BioRestorative, BRTX or the Company) (NASDAQ:BRTX), a clinical stage company focused on stem cell-based therapies, today announced that the United States Patent and Trademark Office has issued a notice of allowance for a patent application related to the Companys metabolic ThermoStem program. The notice of allowance was issued on February 24, 2023.

This will be the third patent granted under this particular family of intellectual property, claims granted under the new patent cover implantable three-dimensional scaffolds and brown adipocytes that have been derived from human brown adipose-derived stem cells. Therapeutic benefits of using brown adipose have been demonstrated in various models and may provide a valuable therapeutic tool for treating a range of metabolic disorders. In addition, BioRestorative is evaluating the use of this technology to target indications outside of metabolic disorders.

This is the second notice of allowance we have received regarding our ThermoStem program within 2023. This notice of allowance is very meaningful as it provides the Company with further protection and strengthens our technology as we develop and expand into the clinic. Additionally, it enhances our ability to engage with the strategic community on collaborative and partnering opportunities said Lance Alstodt, the Companys CEO.

About BioRestorative Therapies, Inc.

BioRestorative Therapies, Inc. (www.biorestorative.com) develops therapeutic products using cell and tissue protocols, primarily involving adult stem cells. Our two core programs, as described below, relate to the treatment of disc/spine disease and metabolic disorders:

Disc/Spine Program (brtxDISC): Our lead cell therapy candidate,BRTX-100,is a product formulated from autologous (or a persons own) cultured mesenchymal stem cells collected from the patients bone marrow. We intend that the product will be used for the non-surgical treatment of painful lumbosacral disc disorders or as a complementary therapeutic to a surgical procedure. TheBRTX-100production process utilizes proprietary technology and involves collecting a patients bone marrow, isolating and culturing stem cells from the bone marrow and cryopreserving the cells. In an outpatient procedure,BRTX-100is to be injected by a physician into the patients damaged disc. The treatment is intended for patients whose pain has not been alleviated by non-invasive procedures and who potentially face the prospect of surgery. We have commenced a Phase 2 clinical trial usingBRTX-100to treat chronic lower back pain arising from degenerative disc disease.

Metabolic Program (ThermoStem): We are developing a cell-based therapy candidate to target obesity and metabolic disorders using brown adipose (fat) derived stem cells to generate brown adipose tissue (BAT). BAT is intended to mimic naturally occurring brown adipose depots that regulate metabolic homeostasis in humans. Initial preclinical research indicates that increased amounts of brown fat in animals may be responsible for additional caloric burning as well as reduced glucose and lipid levels. Researchers have found that people with higher levels of brown fat may have a reduced risk for obesity and diabetes.

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including, without limitation, those set forth in the Company's latest Form 10-K filed with the Securities and Exchange Commission. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.

CONTACT:Email:ir@biorestorative.com

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BioRestorative Therapies Receives Notice of Allowance by the ... - GlobeNewswire