Regeneration of the heart: from molecular mechanisms to clinical … – Military Medical Research

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Stem Cells and Regenerative Medicine: Biotech’s Impact on Health – Digital Journal

PRESS RELEASE

Published April 27, 2023

Stem cells are undifferentiated cells that can differentiate into various types of specialized cells in the body. They can self-renew and regenerate, making them unique and critical for developing, growing, and repairing tissues and organs in the body. Regenerative medicine is a field of biotechnology that utilizes the properties of stem cells to restore, replace, or regenerate damaged or lost tissues and organs in the body.

Biotechnology plays a significant role in advancing healthcare, particularly in regenerative medicine. Biotech has enabled scientists to isolate and manipulate stem cells, develop innovative therapies, and create new technologies for tissue engineering, gene editing, and cell-based therapies. These advancements can revolutionize healthcare by providing new treatments for previously untreatable diseases and conditions.

The impact of stem cells and regenerative medicine on health has been significant. Stem cell therapies have shown promising results in treating various conditions, including cardiovascular diseases, neurodegenerative diseases, diabetes, autoimmune diseases, and tissue injuries. Regenerative medicine approaches, such as tissue engineering and organ transplantation using stem cells, can address the shortage of organs for transplantation and improve outcomes for patients with organ failure. Additionally, stem cells are used in research to study disease mechanisms, drug discovery, and personalized medicine.

Furthermore, stem cells and regenerative medicine can potentially change the way healthcare is delivered, shifting from traditional symptomatic treatment to a regenerative approach that aims to restore the function of damaged tissues and organs. This could result in longer-term and more effective treatments with fewer side effects, leading to improved quality of life for patients.

Stem cells and regenerative medicine are promising in advancing healthcare and addressing unmet medical needs. Continued research and development in biotechnology and regenerative medicine have the potential to revolutionize healthcare and significantly impact human health and well-being.

Lets explore some of the biotechs impact on health thanks to stem cells and regenerative medicine.

The Basics Of Stem Cells

Stem cells are special cells that can develop into different types of cells in our body. There are three main types of stem cells:

Embryonic stem cells

These stem cells come from very early-stage embryos and can develop into any type of cell in the body. They can be used in regenerative medicine to repair or replace damaged tissues or organs.

Adult stem cells

These stem cells are found in various tissues and organs of our body, such as bone marrow, skin, and muscles. They have a more limited ability to develop into specific cell types and are mainly responsible for repairing damaged tissues in the body.

Induced pluripotent stem cells (iPSCs)

These stem cells are created by reprogramming adult cells, such as skin cells, to have properties similar to embryonic stem cells. Like embryonic stem cells, iPSCs have the potential to develop into different cell types and can be used in regenerative medicine.

Stem cells possess three important properties:

The potential applications of stem cells in regenerative medicine are vast and include the treatment of various diseases and conditions, such as heart disease, diabetes, neurodegenerative diseases, and tissue damage caused by injuries or trauma. Stem cells hold great promise in advancing the field of medicine and improving human health by offering new ways to repair, replace, or regenerate damaged tissues and organs. However, further research and ethical considerations are important in harnessing the full potential of stem cells for therapeutic purposes.

What is Regenerative Medicine?

Regenerative medicine is a field of medicine that focuses on repairing, replacing, or regenerating damaged or diseased tissues or organs in the body. It utilizes techniques such as stem cell therapy, tissue engineering, and gene editing to restore normal function to tissues or organs that have been damaged by injury, disease, or aging.

Regenerative medicine stimulates the bodys natural healing processes and promotes tissue regeneration to restore healthy structure and function. It holds promise for treating a wide range of conditions, from chronic diseases to traumatic injuries, and can revolutionize medical treatments by providing innovative solutions for repairing and replacing damaged tissues or organs in the body.

The Importance of Regenerative Medicine

Regenerative medicine holds significant importance in several areas of healthcare and medical research due to its potential benefits, including:

Regenerative medicine has the potential to revolutionize healthcare by offering new treatment options, improving patient outcomes, reducing healthcare costs, and advancing scientific knowledge, making it a field of significant importance in the medical community.

Conclusion

The field of stem cells and regenerative medicine has the potential to significantly impact health and healthcare. With the ability to repair, replace, or regenerate damaged tissues and organs, regenerative medicine offers new treatment options for conditions that currently have limited or no cure. By leveraging the properties and characteristics of different types of stem cells, regenerative medicine holds promise for addressing various diseases, injuries, and degenerative conditions that affect human health.

The importance of biotechnology in advancing regenerative medicine cannot be overstated. Advances in stem cell research, tissue engineering, and gene editing techniques have paved the way for innovative approaches in regenerative medicine, with the potential to revolutionize medical treatments and improve patient outcomes. Additionally, regenerative medicine has the potential to reduce the need for invasive procedures, offer personalized and targeted treatments, advance scientific knowledge, and stimulate economic growth.

FAQ

Which stem cell types are suitable for use in regenerative medicine?

Mesenchymal stem cells (MSCs), which can be readily extracted from adipose tissue and grown in vitro, have emerged as a promising target for tissue regeneration. These cells have frequently been used in human therapeutic trials as well as cell transplantation in animals.

How do stem cells contribute to the regeneration process?

Because they can differentiate into a variety of different cell types and replicate themselves millions of times, stem cells serve a crucial role in regeneration that more specialized cells like nerve cells cannot.

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Stem Cells and Regenerative Medicine: Biotech's Impact on Health - Digital Journal

WUR animal scientists turn to organoids to study swine nutrition – National Hog Farmer

An organoid is a tiny, simplified version of an organ derived from stem cells. They replicate much of the complexity of an organ and have become known from human research. Wageningen University andResearch is growing, for example, mini-guts from pigs and fish and mini-airways from cows and pigs to study animal nutrition and health. Animal scientists Soumya Kar and Esther Ellen answer five questions about their latest developments and future work.

1. In animal research, organoids are something new, aren't they?

"Yes, within WUR we started developing organoids from pigs. Now we are still one of the pioneers in this particular field," Kar said. "There are very few labs in the world that are currently working on the same thing. But, of course, much more research has been done on human organoids. This started around 2010 at the Hubrecht Institute. After a decade, these organoids have already achieved a lot in nutritional and pharmaceutical research and they are also pretty instrumental in diagnostics and even clinical treatment. So the human field is years ahead of what we're doing in livestock. I think we're just getting started."

2. Why do we need these miniature organs in livestock research?

"We see organoids as a good tool to replace animal experiments. They help to answer research questions in animal breeding and animal nutrition," Ellen said. "For instance, why some pigs use feed more efficiently than other pigs. This is a quite complex trait of an animal. Organoid research can help us identify differences between individual animals. Our organoids are also useful to test specific ingredients of animal feed. In the future they might also be valuable for questions on animal health and pharmaceutics."

"So we use pigs with different genes for our organoids," Kar said. "Let's say we have pigs with genes providing a high feed efficiency and other pigs with genes for a low efficiency. Then we derive organoids from their intestinal stem cells and try to understand the differences in their functioning."

"If we are able to use organoids to understand complex traits, then we can also use them as a tool for selecting animals more specifically for new traits, without increasing the number of animal experiments. For example, traits like nutrient utilization and manure production. That's what we would like to achieve," said Ellen.

3. Do you think it will make a big difference in the number of animal experiments?

"I think organoids will play a crucial role in the search for alternatives for animal testing. That's our moral responsibility as animal researchers," Kar said. "Theoretically, many organoids from different tissues can be obtained from a single animal. This will help reduce the use of animals in experiments. However, we can't completely get rid of all animal experiments because organoids are still different from whole animals. But by using organoids some animal experiments aren't necessary anymore."

4. Can other researchers already knock on your lab's door if they want to collaborate?

"Yes, we are very open for collaboration and think that this is important to further explore this emerging field in human and animal sciences," Ellen said. "Researchers are very enthusiastic about our organoids, so we're continuing our pioneering work."

5. What are your next steps as organoid developers?

"There are still so many questions that need to be solved in order to make our system more reproducible and overcome practical issues," Kar said. "We are also working on other improvements. An organoid now contains one type of cell, because we start with adult stem cells. They are programmed to proliferate and differentiate into their own lineages. Thats why blood vessels, neurons and immune cells are not yet part of the organoid. In the coming years we intend to study mixing and matching different cell lineages, for example an epithelial layer (intestinal cells in contact with food) with the immune cells. A system like this can be used to understand host-microbe interactions or diet-host interactions."

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WUR animal scientists turn to organoids to study swine nutrition - National Hog Farmer

BrainStorm Cell Therapeutics Strengthens Leadership Team with … – PR Newswire

Dr. Taylor has extensive biopharma industry expertise in neurodegenerative disease and experience leading drug launches and post-approval studies

Company begins a targeted capability build to prepare for anticipated growth

NEW YORK, April 24, 2023 /PRNewswire/ --BrainStorm Cell Therapeutics Inc.(NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, today announced the appointment of Kirk Taylor, M.D., as Executive Vice President and Chief Medical Officer (EVP, CMO), effective May 1, 2023. Dr. Taylor will serve on BrainStorm's executive leadership team reporting to Stacy Lindborg, Ph.D., co-CEO of BrainStorm.

Dr. Taylor will lead the global medical affairs function and launch activities, including product launches, post-approval commercialization efforts and deepening relationships with the medical community. He will also support clinical development and overall corporate strategy, including advancement of the Company's long-term business model.

"Kirk's appointment is the first important step in strengthening a targeted, capability build to expand our medical, regulatory and advocacy teams in preparation for anticipated growth," said Chaim Lebovits, President and CEO of BrainStorm. "His experience as a practicing neurologist and building and leading global medical teams will be an invaluable asset as we work to advance NurOwn to regulatory review with the goal of making it widely available to individuals with ALS. We are thrilled to welcome Kirk to BrainStorm and look forward to the contributions he will make."

BrainStorm Cell Therapeutics is entering a pivotal time, as the company prepares for regulatory review of the company's Biologics License Application (BLA) for NurOwnfor the treatment of amyotrophic lateral sclerosis (ALS). On March 27, 2023, BrainStorm announced that the U.S. Food and Drug Administration intends to hold an Advisory Committee meeting to prepares for FDA review of NurOwn for the treatment of amyotrophic lateral sclerosis (ALS).

Dr. Taylor remarked, "It is an honor to join BrainStorm. This is an exciting time for the company and the ALS community. I am encouraged by the regulatory flexibility that the FDA has shown these rapidly progressing neurological illnesses, such as ALS, where patients are in dire need of new treatments now. I am confident in the effectiveness of NurOwn and grateful for the opportunity to review the full body of clinical evidence with the entire stakeholder community. Time is of the essence for people with ALS and I am ready to hit the ground running."

Dr. Taylor has more than 26 years of experience in global drug development programs, from Phase 1 through post-approval studies, across multiple therapeutic areas including neurology and rare diseases. He is joining BrainStorm from EMD Serono (a Merck KGaA, Darmstadt, Germany company), where, as Senior Vice President, North American Medical Affairs, he led the medical team's efforts across four therapeutic areas and the launch of three new treatments. Prior to EMD Serono, Dr. Taylor served as Senior Vice President, Medical Affairs Strategy and Operations at Verastem Oncology and CMO and Chief of Strategy and Late Phase Development at Finch Therapeutics Group, where he created a plan for filing and commercializing the company's internal assets. Earlier in his career, Dr. Taylor held high-prominent medical roles at companies such as Biogen, Pfizer and Sanofi-Genzyme.

Dr. Taylor holds a B.A. from Harvard University and a M.D. from University of New York Downstate Health Sciences University. He completed a neurology residency at the Albert Einstein College of Medicine and a postdoctoral fellowship in pain management at the University of California, San Francisco. He taught pain management to neurology residents while on faculty at Yale VA Hospital for two years. He also completed executive leadership training at Harvard, Stanford and INSEAD business schools.

About NurOwn

The NurOwn technology platform (autologous MSC-NTF cells) represents a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells are designed to effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression.

AboutBrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug designation status from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has completed a Phase 3 pivotal trial in ALS (NCT03280056); this trial investigated the safety and efficacy of repeat-administration of autologous MSC-NTF cells and was supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). BrainStorm completed under an investigational new drug application a Phase 2 open-label multicenter trial (NCT03799718) of autologous MSC-NTF cells in progressive MS and was supported by a grant from the National MS Society (NMSS).

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding BrainStorm's Type A meeting with the FDA and the clinical development of NurOwnas a therapy for the treatment of ALS, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "intend," "should," "could," "will," "believe," "potential," and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, management's ability to successfully achieve its goals, BrainStorm's ability to raise additional capital, BrainStorm's ability to continue as a going concern, prospects for future regulatory approval of NurOwn, whether BrainStorm's future interactions with the FDA will have productive outcomes, the impacts of the COVID-19 pandemic on our clinical trials, supply chain, and operations, and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available athttp://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations, and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, or achievements.

CONTACTS

Investor Relations:John MullalyLifeSci Advisors, LLCPhone: +1 617-429-3548[emailprotected]

Media:Lisa GuitermanPhone: +1 202-330-3431[emailprotected]

Logo: https://mma.prnewswire.com/media/1166536/BrainStorm_Logo.jpg

SOURCE BrainStorm Cell Therapeutics Inc.

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‘This is simply mind-blowing’: Monkeys implanted with synthetic … – Genetic Literacy Project

Embryos made from stem cellsinstead of a sperm and egghave been created from monkey cells for the first time. When researchers put these synthetic embryos into the uteruses of adult monkeys, some showed the initial signs of pregnancy. Its the furthest scientists have ever been able to take lab-grown embryos in primatesand the work hints that it may one day be possible to generate fetuses this way.

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But within 20 days of transfer, the monkey blastoids stopped developing and seemed to come apart, say [researcher Zhen] Liu and colleagues, who published their results in the journal Cell Stem Cell. This suggests the blastoids still arent perfect replicas of normal embryos, says Alfonso Martinez Arias, a developmental biologist at Pompeu Fabra University in Barcelona, Spain. For the time being, it clearly doesnt work, he says.

That might be because a typical embryo is generated from an egg, which is then fertilized by sperm. A blastoid made from stem cells might express genes in the same way as a normal embryo, but it may be missing something crucial that normally comes from an egg, says Martinez Arias.

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'This is simply mind-blowing': Monkeys implanted with synthetic ... - Genetic Literacy Project

NICE approves expanded use of Yescarta and Tecartus – PharmaTimes

Kites two CAR T-Cell therapies involve treating several different types of blood cancer

Kite a Gilead Sciences spin out company has announced that the National Institute for Health and Care Excellence (NICE) has recommended additional uses for their two CAR T-cell therapies.

The treatments represent options for the treatment of certain blood cancers for the Cancer Drugs Fund (CDF). Kite currently has two CAR T-cell therapies now available across the NHS covering four types of blood cancer.

Firstly, Yescartahas been recommended for treating adult patients with diffuse large B cell lymphoma (DLBCL) that relapses within 12 months of first-line treatment.

Data supporting its use is based on primary results of the pivotal phase 3 ZUMA-7 study. Herein, the primary endpoint was event-free survival (EFS). The 24-month EFS was 40.5% in the Yescarta arm and 16.3% in the standard-of-care element.

Furthermore, Kites second CAR T-cell therapy Tecartus is now available as an option for adult patients of 26 years of age and above, with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL).

Data supporting its use was observed during the ZUMA-3 single-arm trial. In the combined phase 1/2 data set, 73% of the analysed individuals treated with Tecartus achieved overall complete remission, as determined by an independent review.

Dr Sridhar Chaganti, consultant haematologist at Queen Elizabeth Hospital, Birmingham, explained: "This decision is a pivotal moment for expanding how CAR T-cell therapy is used to treat DLBCL until now, these therapies have been reserved for use when patients have failed traditional standard of care and had few options remaining. With todays announcement, we will now have the option to use it earlier for some patients, potentially creating a new pathway and standard of care."

David Marks, professor of haematology and stem cell transplantation, added: The approval of this CAR T-cell therapy for adult patients with acute lymphoblastic leukaemia represents an important change for adult all patients.

He concluded: In addition, certain high-risk patients who cant achieve or maintain deep remissions, or who are unsuitable for alloHSCT, are now eligible for CAR T-cells. In ALL, patients less than 26 years old have had the option of therapy with CAR T-cells for some time and this approval now ensures patients of all ages can access the latest scientific advances.

CAR T-cell treatments are made starting from a patients own white blood cells. The cells are removed through a process similar to donating blood platelets and sent to Kites specialised manufacturing facilities where they are engineered to target the patients cancer.

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NICE approves expanded use of Yescarta and Tecartus - PharmaTimes

Study finds alternative to hip replacement – Daily Trust

A new study has revealed that adult stem cell therapy is effective as an alternative to total hip replacement surgery in severe hip osteoarthritis.

Adult stem cell therapy, a subcategory of regenerative medicine, revitalizes and regenerates the bodys organs and systems. Regenerative medicine experts say it also reverses and repairs many pending subclinical medical problems before they become apparent, including diseases that are age-related, which conventional treatments cannot do.

The study, published in this months edition of the Journal of International Case Reports (ICARE), was led by Dr David Ikudaiyisi, Medical Director of Glory Wellness and Regenerative Centre in the USA, Lagos and Abuja.

It was aimed at evaluating the importance of adult stem cell therapy as an alternative to total hip arthroplasty in severe hip osteoarthritis.

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Hip osteoarthritis is one of the leading causes of chronic hip joint pain and disability worldwide. According to the arthritis research and therapy, the global incidence of hip osteoarthritis from 1990 to 2019 increased from 0.74 million to 1.58 million.

The disease causes gradual loss of range of motion and is most often symptomatic during weight-bearing activities. Pain may be felt in the inguinal area or greater trochanter or referred to the thigh and knee, and it is usually accompanied by stiffness of the affected joint.

It is one of the leading causes of chronic hip joint pain and disability worldwide affecting older age individuals: usually symptomatic in the 40s and 50s and is nearly universal by age 80.

Hip replacement surgery, or hip arthroplasty, is a surgical procedure in which an orthopaedic surgeon removes the diseased parts of the hip joint and replaces them with new, artificial parts.

The study followed up a patient for 24 months. The case report started on th 13/11/2020.

Diagnosed with severe bilateral hip osteoarthritis. The patient had a left total hip arthroplasty for left severe hip osteoarthritis one and a half years prior to presentation and wished to have a procedure with adult stem cell therapy on the right hip as she did not want another surgical procedure done.

The patient provided written informed consent to undergo the experimental clinical procedure as well as consent to publication of outcomes, images, and data.

The treatment was done in three sessions. The first session was a combination of MSCs {ADSCs (svf) and BMAC} plus PRP. The second session was a combination of allogenic exosomes plus PRP done at six months. The third session was a combination of Stromal Vascular Fraction (SVF) plus PRP done at 10 months.

The Right hip severity was assessed using the Harris Hip Score (HHS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale. Radiologic studies (X-ray and MRI) were done.

The results showed a positive outcome according to all the grading systems used in the study and the patient was followed up for 24 months and is still being followed up which is proving its advantage in long-term outcomes.

The research concluded that adult stem cell therapy is a promising alternative method of treatment in people with severe hip osteoarthritis.

Dr David Ikudaiyisi, said regenerative medicine involving adult stem cells is continually being studied and researched to gather more evidence to enable harnessing its clinical potential.

The use of adult stem cells for clinical therapy is now a reality for many patients who were not able to shed the yoke of many diseases that conventional medicine provided very little hope of permanent relief for.

He said, Currently, adult stem cell therapy is now seen as a viable therapeutic alternative for joint and back pain, sexual dysfunction, diabetes, End Stage Renal Disease on hemodialysis, arthritis, etc.

The treatments are gaining popularity among patients and doctors because it is natural and can help repair and regenerate most parts of the human tissues.

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Study finds alternative to hip replacement - Daily Trust

Gene therapy for sickle cell disease treatment brings hope to patients – The Washington Post

April 28, 2023 at 3:13 p.m. EDT

DACULA, Ga. For as long as he can remember, Jimi Olaghere felt he was destined to be a father. Its so true in my soul, he told his wife, Amanda, when they struggled to get pregnant. But when they were finally expecting a baby boy in 2019, joy was tinged with despair.

For 34 years, sickle cell disease had been hammering Jimis body and stealthily shredding his ambitions. He knew it would come for his dream of being a dad, too.

Inside Jimi, normally pliable, disc-shaped red blood cells deformed into rigid crescents. Those microscopic sickle-shaped cells clumped together, unleashing a cascade of damage. Pain was a constant, but about once a month it erupted into pure agony like glass had shattered inside his veins and shards were sawing back and forth.

How would monthly trips to the emergency room to manage his pain work with a newborn baby? Could he keep up with a toddler when everyday pain could keep him stuck in bed all day? Would he even live long enough to try?

I knew sickle cell would win that battle as well, Jimi said. It won everything with my career, with education, with everything I wanted to do.

Then, midway through Amandas pregnancy, the couple read an article about Victoria Gray, a woman whose genes had been experimentally edited to treat her sickle cell disease. It was still too soon to know exactly how well it worked, but Jimi wanted in.

After decades of neglect, stigma and underfunding, sickle cell is getting the equivalent of the red carpet treatment in science. Its the target of a competitive biotech race, with scientists and companies using a crop of cutting-edge tools to try to cure the debilitating illness.

The first gene therapies for sickle cell, including one based on the buzzy, Nobel Prize-winning technique called CRISPR, will be reviewed by regulators this year, and companies are preparing to launch the medicines if they get the green light. That puts the country at the cusp of two frontiers: a new era in treating a tragically overlooked disease, and the beginning of what could be a CRISPR revolution in medicine.

Its a dramatic about-face for sickle cell patients, who have often felt abandoned by the medical system. The rare disease afflicts about 100,000 people in the United States, most of them Black. Racism at both the institutional and interpersonal level has stymied funding and alienated patients, who are often treated as drug-seekers when they show up in emergency rooms in acute pain.

Of course theres skepticism. This is a disease thats been left to just succumb to the health-care system for so long, and suddenly this influx of money and parties and pharmaceutical companies [and] a whole staff of White folks want to come in and ask us about our disease, said Ashley Valentine, president of Sick Cells, a patient advocacy group that she founded with her brother Marqus, who died of a hemorrhagic stroke at age 36.

There are risks and unknowns with any new technology; one doctor told Jimi the magnitude of the challenge was comparable with landing on the moon for the first time. But the doctors, patients and others eager for sickle cell treatments say that turning gene editing into a viable therapy, then finding ways to make it widely accessible, will help carve a path for others to follow.

The hope, said Valentine, is that if the feds and governments and society can figure this out with sickle cell, they can figure this out with other diseases.

Decades before Jimi was born, chemist Linus Pauling discovered the root of the problem in sickle cell disease: an atypical form of the oxygen-carrying hemoglobin protein inside red blood cells. He dubbed sickle cell the first molecular disease a new paradigm that would shape biomedical research for decades.

Hard scientific work would fill in the rest of the story. The human genetic code is a string of 3 billion letters, each representing one of four molecular building blocks. Atypical hemoglobin is the result of a misspelling in one gene a T where there should be an A. People with just one copy of the altered gene have sickle cell trait. They live without major health symptoms, and even have an advantage: better protection against malaria. But people with two copies can experience devastating symptoms and die decades early.

Jimis parents had sickle cell trait. So did an older sister. But he had sickle cell disease. As a child growing up in Nigeria, it was hard to keep up with his friends energy levels. The pain episodes would arrive at night, or after tough exertion. His parents used menthol rubs and over-the-counter painkillers to try to ease his discomfort, which was so intense he would pass out.

Eventually, Jimi moved to live with relatives in New Jersey so that he could take advantage of better medical care. At a sickle cell support group, Jimi began to understand how deeply the disease infiltrated every aspect of daily life. It wasnt just hospitalizations and pain. A girl shared that she would eat random objects a condition called pica that often accompanies the disease. He recognized his own tendency to scrounge chalk and rubbish to eat, which had always made him feel as if he were going crazy.

The disease often gets worse as patients get older, which tragically coincides with a medical cliff in the U.S. health-care system. Children have parents and pediatric hematologists who are devoted to managing their disease. As adults, they have to coordinate their own care and are often treated very differently. Most people who have the disease in the United States are Black, and they are often met with suspicion and hostility, not compassion when they show up in the emergency room in excruciating pain.

As he got older, Jimis pain episodes became so frequent that they bled together in his memory. One time, his fever spiked so high that he lost consciousness. Jimi woke up in the intensive care unit a day later, disappointed to still be alive.

There became a point of my life I stopped going to the emergency room and started medicating at home, Jimi said. I was just so embarrassed.

He suffered a heart attack in his 20s. He developed blood clots in his lungs. His hips sometimes ache because parts of the bone tissue in his joints died because of lack of oxygen delivery.

Until recently, there werent many treatments for sickle cell disease. A bone-marrow transplant could cure it by providing patients with marrow that made normal hemoglobin, but a suitable match from a sibling could be found for only about 1 in every 5 patients. Then theres hydroxyurea, the first and only drug that was approved to treat sickle cell until 2017; three drugs have been approved since then. Hydroxyurea helps keep red blood cells from sickling, or deforming into a sickle shape, by increasing levels of a type of fetal hemoglobin that is switched off after birth.

Research into the disease gave scientists two main avenues for gene therapy. One would be to replace the gene or correct the genetic typo to restore normal hemoglobin production. Another would be to get the body to start pumping out fetal hemoglobin again.

The ideas were straightforward, but progress was slow. The field was underfunded, in part because the Black population historically lacks access to the intergenerational wealth, influence and privilege that fuels private philanthropy for rare-disease research. Even at the federal level, other rare diseases that cut short peoples life spans such as the lung disease cystic fibrosis received triple the funding per person until the gap began to narrow in 2017.

Theres huge underinvestment, said Stuart Orkin, an expert in the field and professor of pediatrics at Harvard Medical School and the Dana-Farber Cancer Institute. The NIH probably wouldnt like me to say this, but one of the goals of the National Heart, Lung and Blood Institute is to cure sickle cell disease. They certainly have not put the kind of resources into it that would be required.

Gary Gibbons, director of the NHLBI, pointed to data showing that federal funding for sickle cell research has doubled since 2010, and he highlighted the Cure Sickle Cell Initiative that was launched in 2018. NHLBI is committed to improving the care and long-term survival for children and adults with sickle cell disease in the U.S. as well as other parts of the world, Gibbons said.

A turning point occurred when sickle cell became an attractive target for companies to invest in as new gene therapy techniques reached prime time and better understanding of the disease clarified the best therapeutic strategies.

Fifteen years ago, scientists pinpointed a gene called BCL11A that worked like a dimmer switch, controlling the amount of fetal hemoglobin the body produced. When scientists shut it off, fetal hemoglobin expression turned back on. In 2011, Orkins lab showed that it was possible to reverse sickle cell disease in mice by flicking the BCL11A switch.

At the same time, a growing array of gene therapy techniques gave scientists tools to flip genetic switches or insert new genes kicking off a flurry of competing sickle cell cures. CRISPR, discovered in 2012, is being used to edit a key region of the BCL11A gene to turn fetal hemoglobin back on. Other approaches use a harmless virus as a kind of Trojan horse to insert a new version of the hemoglobin gene that resists sickling into a patients stem cells. Yet another uses a specialized RNA molecule to silence BCL11A.

After years of little progress, there wasnt just one way to treat sickle cell there were many.

I have wanted to see this succeed for 40 years, said Francis Collins, the former NIH director whose postdoctoral research in the early 1980s was on sickle cell. I thought wed be lucky if in my lifetime, if we achieved even a single cure of someone for sickle cell disease.

Out of nowhere, I could tell it was gone

For most of his life, Jimi had a hard time envisioning the future. How many times had people told him he wouldnt live to see his 20th or 30th birthday? On his first date with Amanda, when they were in their early 20s, he put down the menu and told her he had sickle cell, and that he understood if that was a dealbreaker.

Im super competitive, and I said, Ill take it on, Amanda recalled, laughing. She went home and began Googling to learn more about the disease.

To manage Jimis sickle cell, the couple forged a powerful partnership. They could handle anything together. But with a baby on the way, the stakes changed.

I thought I was going to die, Jimi said. I thought, I cant leave my wife with a son and not be here for them.

In November 2019, Jimi and Amanda flew to Nashville to meet with Haydar Frangoul, the pediatric hematologist leading a trial of a CRISPR gene therapy for sickle cell disease at Sarah Cannon Research Institute. They learned shortly after Christmas that Jimi qualified for the trial. Their son, Sebastian, had just been born. It felt like a gift.

From start to finish, Jimis treatment would take the better part of a year. First, his stem cells needed to be collected from his blood. This required long car trips to Nashville and being hooked up to a machine for hours at a time. Once the researchers collected enough stem cells, they edited the cells to disable the BCL11A switch. Then the cells needed to be carefully checked for quality.

Jimi also needed chemotherapy to kill off existing cells in his bone marrow so that his edited stem cells would have room to engraft and grow. His hair fell out and he developed painful sores in his mouth.

Amanda, Jimi and baby Sebastian lived in the hospital for weeks, juggling remote work and the haze of starting their new family life. They set up a playpen in the hospital room. The nurses and doctors became like a second family. Jimi continued to run his e-commerce business from his hospital bed, while Amanda worked remotely, sometimes rushing to a nearby hotel room to do conference calls. Sebastian often napped next to his dad.

When Jimis body was ready to receive the cells, the nurses brought three syringes into the room. Another participant in the trial had warned him: It will smell like creamed corn. Sure enough, the room filled with the aroma, due to a preservative used to freeze the cells. His parents watched through a live feed from Nigeria.

Jimi came home at the end of November 2020. As his new edited cells began pumping out fetal hemoglobin, he felt the disease depart.

I had lived 35 years with this disease that sometimes I consider a companion, and out of nowhere I could tell it had gone or was in the process of leaving. We were enmeshed together, and I could feel it detangling, Jimi said.

A year went by, and Jimi had no pain crises.

We can plan in the future like decades in the future now, Amanda said. They got pregnant again using in vitro fertilization, this time with twins.

Carry your cure with you

Jimi is one of 31 participants whose results have been made public in the sickle cell trial run by Vertex Pharmaceuticals and CRISPR Therapeutics. None have had pain crises since their treatment, according to data through February 2022, though at that time, only 11 patients had been followed for at least a year. The companies just finished submitting data to regulators, and the Food and Drug Administration is expected to make a decision on whether to approve the therapy as soon as this year. The therapy is also being tested in the related blood disease beta thalassemia.

Another trial run by Massachusetts-based company Bluebird Bio uses a different gene therapy approach. A patients stem cells are removed, then a virus inserts a gene into them that codes for a non-sickling version of beta-globin, a component of hemoglobin. Bluebird has treated 50 sickle cell patients, six of whom have been followed for six years, and submitted its data to regulators in April. The company has announced it could roll out the therapy in 2024.

The beauty of gene editing for sickle cell is that it takes a lot of the luck out of the equation. People dont have to count on finding a bone marrow match. They also dont have to worry about a dangerous complication that can occur when cells transplanted from another person attack the recipients own tissues.

You carry your cure with you, basically, the Sarah Cannon Research Institutes Frangoul said.

But the challenges of turning an intensive therapy into an accessible medicine are formidable. For instance, chemotherapy is not only time-intensive and unpleasant, but it also causes infertility, meaning patients must have the ability to put their lives on hold for the treatment and have the time and resources to make long-term plans about future reproductive choices.

The first gene therapies for sickle cell will be a turning point, but it will take years and many millions of dollars to reach even a fraction of the patients who could benefit. Jimi did not have to pay for his treatment because it was part of a clinical trial, and the companies have not yet announced the price tag. A draft report by the Institute for Clinical and Economic Review, a nonprofit that examines whether drugs merit their prices, found that charging $2 million per treatment could be cost-effective for patients with severe disease, leading to health gains and lifetime opportunities.

Already, the success of the front-runners is winnowing out competition, as some companies drop their sickle cell gene therapy programs. The trend disappoints scientists who worry that a winner-takes-all model will leave important scientific questions unsettled about which approach is superior.

Jimi says he feels like hes cured, though he knows it isnt the correct word. Frangoul will follow Jimi and other patients for 15 years to track their health and monitor them for side effects.

Two patients in Bluebirds trial developed acute myeloid leukemia and died; extensive studies found that the cases were not likely to be related to the insertion of the new gene.

If both of the therapies being submitted are approved, they probably will be limited to severely ill people at first. Vertex officials estimate there are about 25,000 people in the United States in that category, and they have outlined plans to partner with 50 treatment centers in the United States and 25 in Europe.

Im excited but I dont expect to see my job different two years from now because we have a gene therapy, said John J. Strouse, a hematologist at Duke University School of Medicine who treats adult sickle cell patients.

Frangoul said the questions of access and insurance coverage already worry him. He recalled the early days of bone marrow transplants to treat sickle cell, when he would write appeal after appeal to insurers to try to get the novel procedure covered.

Jennifer Doudna, the biochemist at the University of California at Berkeley who shared the Nobel Prize for discovering CRISPR, said that she anticipates feeling sheer joy when the first CRISPR therapy is approved, but also urgency.

A nonprofit she founded, the Innovative Genomics Institute, is working on a different CRISPR therapy to correct the genetic typo in sickle cell disease. Institute leaders also hope to pioneer a less-conventional business model in which creative partnerships between industry, government, academia and nonprofits could lead to new ways to price very expensive drugs for rare diseases.

I think its going to make me feel even more motivated, Doudna said. People need this therapy, right? And people cant pay millions of dollars for it.

After Jimis treatment, he had a different kind of crisis: Who am I without sickle cell?

After a lifetime of constant pain, it was disconcerting to have none. He felt guilty for not being elated that he was finally well, but he mourned the years of lost potential that he had spent as a prisoner of sickle cell.

The physical toll of the disease sickle cell itself doesnt compare to the emotional vacuum it creates, he said.

At the same time, he looks at his life now with a bit of wonder.

He stands a little taller, and he no longer wears glasses to obscure his eyes, which were severely jaundiced because of the disease. After years of being unable to sleep at night because of pain and taking naps during the day, he wakes up at 4:30 a.m. feeling like he chugged a Red Bull. He meditates, works, then wakes his twin daughters, Eloise and Willow, and gives them breakfast. The soundtrack in his household is kid-friendly songs and discussions of dinosaurs.

To me, it still feels special the amount of energy I have, he said.

The story doesnt end with him. Some of Jimis relatives in Nigeria have sickle cell disease. Three of Jimis children are carriers of the sickle cell trait. He wants to make sure other people with sickle cell have the opportunity to free themselves from the disease not only the patients in the United States, but also the 20 million people in the rest of the world, many of them in sub-Saharan Africa, India and the Middle East.

Extending gene therapies to more populations will require big leaps in science. A major quest is on to invent ways to deliver gene therapies without an intensive bone marrow transplant. And Jimi wants people in the next generation, regardless of where they live, to have the opportunity to grow up without the shadow of illness.

If by Gods grace we cure 100,000 people [in the United States], thats not even a fraction of the people that actually suffer with the disease in West Africa, India and all those regions where its quite prevalent, Jimi said. Most of my advocacy is shining a light to all of these places that are still in the background for now.

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Gene therapy for sickle cell disease treatment brings hope to patients - The Washington Post

Alzheimer’s: Study pinpoints key role of glucose in brain activity – Medical News Today

The brain requires large amounts of energy to function. Glucose is the primary fuel for neurons. While the adult brain accounts for 20-25% of glucose consumption, developing brains may require an even higher quantity.

How glucose is processed in the brain, however, has remained unknown. Some have suggested that glucose may be metabolized by supporter glial cells and then exported to neurons.

More recent studies suggest that neurons may be able to process glucose on their own. It has been difficult to determine whether this is the case due to difficulties in isolating neurons from glial cells for study.

Understanding how glucose is metabolized for energy in the brain could pave the way for new treatments for conditions linked to glucose uptake, such as Alzheimers disease (AD) and Parkinsons disease (PD).

Recently, researchers conducted cell and mouse studies to assess how glucose is metabolized by neurons.

They found two proteins that make it possible for neurons to metabolize glucose themselves both in cell cultures and in animal models.

Dr. Charles Munyon, a functional neurosurgeon with Novant Health in Charlotte, North Carolina, who was not involved in the study, told Medical News Today:

These findings appear to settle a long-standing controversy fairly definitively, and the study is elegantly designed. While it is still not clear what proportion of neuronal energy comes from direct glucose metabolism, we can be certain that the answer is not negligible.

The study was published in Cell Reports.

For the study, the researchers used induced pluripotent stem cells (iPSCs) to generate human neurons. They then added the neurons to a labeled form of glucose. In doing so, they found that neurons were able to break down glucose into smaller metabolites.

Next, the researchers removed two key proteins for importing and metabolizing glucose from the neurons using CRISPR gene editing. Removing either of these proteins impaired the breakdown of glucose in the human neurons.

This, noted the researchers, means that human neurons indeed metabolized glucose.

The researchers next wanted to see whether the findings translated to animal models. To do so, they engineered neurons in mice to lack the same two key proteins for glucose import and metabolism.

The mice that lacked one of the proteins showed normal memory and learning at 3 months of age, but at 7 months they showed severe learning and memory deficits. For the other tested protein, while both female and male mice had normal memory at three and seven months old, they noted that femalesbut not malesdeveloped learning and memory loss by 12 months.

The researchers noted that further studies are needed to understand what may explain the sex differences.

Lastly, they investigated how neurons adapt when glucose is not available as an energy source. They found that neurons use other energy sources, such as a related sugar molecule, galactose, which was less efficient than glucose as an energy source for the neurons.

The researchers concluded that neurons metabolize glucose by themselves and that they require glucose metabolism for normal function.

When asked about the studys limitations, Dr. James Rini, a neurologist at Ochsner Health, who was also not involved in the study, told MNT that as the study was conducted in mice and in a lab setting, it remains unclear if the findings apply to humans and real-life settings too.

He added that the method used to measure glucose metabolism may not capture the full picture of how neurons metabolize glucose in the brain.

[Furthermore], the study only looked at one aspect of brain functionhow neurons metabolize glucoseand did not investigate other factors that may contribute to brain function, such as the role of other nutrients or neural signaling pathways, he explained.

MNT also spoke with Dr. Fahmeed Hyder, professor of Biomedical Engineering at Yale School of Medicine, who was not involved in the study, about the studys implications. He noted that the study adds a well-established line of experimental evidence suggesting that neurons metabolize glucose on demand.

When asked about the studys implications, Dr Rini added:

Direct glucose metabolism pathway may be a new target for therapeutic interventions in brain diseases. For example, if researchers can find ways to enhance glucose uptake or utilization by neurons, it may be possible to improve brain function in people with neurological disorders such as AD and PD.

There have been multiple trials already that have suggested this, CTAD 2022 data suggests Januvia may be neuroprotective in AD, he explained.

Dr. Charles Munyon noted, however, that there is no evidence that the findings will impact therapeutics for AD or PD.

While it is true that glucose metabolism decreases in these conditions, this is a secondary effect due to accumulation of amyloid/tau or alpha-synuclein, he said.

In summation, from a basic science standpoint, this is a well-designed study that answered a long-standing question. In terms of how this will likely impact medical treatment, I dont see a significant impact coming at all, he concluded.

The rest is here:
Alzheimer's: Study pinpoints key role of glucose in brain activity - Medical News Today

Reprogramming Fibroblasts in Vivo for Heart Repair – Lifespan.io News

Scientists from Duke University have found a way to make adult fibroblasts differentiate into cardiomyocytes, which might help develop better heart attack treatments [1].

Myocardial infarction, or heart attack, is a leading cause of death and disability. It happens when the blood flow to a part of the heart gets blocked, often by a blood clot, leading to cell death and necrosis [2]. When the blood flow is restored, the healing is similar to that of flesh wounds. Fibroblasts recruited to the area produce a lot of intracellular matrix elements, which results in the formation of stiff scar tissue. This decreases the hearts efficiency, negatively affecting future lifespan and healthspan.

This imperfect repair process reflects the changes we undergo after birth. Fibroblasts are multipotent cells that can differentiate into other cell types, such as adipocytes, chondrocytes, and cardiomyocytes, the heart muscle cells. This process is effective in fetuses and newborns, which is why cuts on a newborns skin often heal perfectly without leaving any scar tissue. However, after a fairly short time, fibroblasts become less inclined to differentiate, preferring to produce the extracellular matrix instead.

Scientists have been looking for ways to trick adult fibroblasts into behaving immaturely, differentiating into myocytes to heal myocardial infarction more effectively [3]. However, attempts at direct fibroblasts to myocytes reprogramming in vivo have been hampered by low reprogramming efficiency. Apparently, its hard to teach old fibroblasts new tricks.

In this new study, the researchers attempted to identify the changes in fibroblasts after birth and how these changes could be manipulated for therapeutic benefits. First, they isolated cardiac fibroblasts from neonatal and adult mice. All fibroblasts were identically passaged: that is, they had undergone roughly the same number of divisions, which made them of a similar cellular age. The fibroblasts were then transfected with a cocktail of four micro-RNAs (miRNAs) that had been shown by previous research to induce reprogramming of fibroblasts into cardiomyocytes, albeit with low efficacy.

Reprogramming worked well in neonatal, but not adult, fibroblasts. The researchers looked at transcription factors that were expressed differently in those two types of fibroblasts and then made several more attempts at reprogramming, each time adding a siRNA (short interfering RNA) to silence one of the candidate factors. Silencing Epas1, which was highly expressed in adult but not neonatal fibroblasts, seemed to work best, robustly increasing the number of reprogramming events in the culture. Conversely, overexpressing Epas1 in neonatal fibroblasts resulted in them losing their remarkable differentiation capacity.

To test their new insights, the researchers inflicted myocardial infarction on mice, and then delivered the reprogramming miRNA combo and the Epas1-blocking siRNA directly into the infarction border zone. Two months after the injury, no new cardiomyocytes appeared in mice that received sham treatment. In mice who received only the reprogramming cocktail, few reprogramming events occurred. However, in the mice that also received Epas1-blocking siRNA, about 20% of resident cardiomyocytes turned out to be former fibroblasts. The treatment also significantly improved cardiac function.

The authors hypothesized about the event that triggers the expression of Epas1 and moves myofibroblasts towards their adult differentiated phenotype. They suggest that this cue might be oxygen deprivation during birth, since low oxygen levels are known to induce Epas1 expression [4]. The researchers mention that low oxygen levels during birth might also be the stimulus behind cardiomyocyte cell cycle exit (adult cardiomyocytes are largely non-proliferative).

The researchers note that while they chose Epas1, which yielded good results, other transcription factors might be at play as well. Targeting several factors at once might lead to even better outcomes. For RNA delivery, the researchers used exosomes, a type of extracellular vesicles used by cells for communication. This method of delivery was popularized by recent COVID-19 vaccines that use it to deliver their RNA cargo.

Regaining the impressive regenerative abilities that we lose soon after birth might be the key to staving off numerous deadly diseases. This research underscores how pliable cell fate can be, and that we might be able to manipulate it to produce new differentiated cells in environments that normally do not allow this. Direct reprogramming of fibroblasts in vivo can also be used outside of the cardiac context, such as in producing new cartilage.

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[1] Sun, H., Pratt, R. E., Dzau, V. J., & Hodgkinson, C. P. (2023). Neonatal and adult cardiac fibroblasts exhibit inherent differences in cardiac regenerative capacity. Journal of Biological Chemistry, 104694.

[2] Ojha, N., & Dhamoon, A. S. (2021). Myocardial infarction. In StatPearls [Internet]. StatPearls Publishing.

[3] Chen, Y., Yang, Z., Zhao, Z. A., & Shen, Z. (2017). Direct reprogramming of fibroblasts into cardiomyocytes. Stem cell research & therapy, 8, 1-8.

[4] Peng, J., Zhang, L., Drysdale, L., & Fong, G. H. (2000). The transcription factor EPAS-1/hypoxia-inducible factor 2 plays an important role in vascular remodeling. Proceedings of the National Academy of Sciences, 97(15), 8386-8391.

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Reprogramming Fibroblasts in Vivo for Heart Repair - Lifespan.io News