BMS and Merck Buy Big Into Amphista's Protein Degradation Platform

 Amphista Therapeutics has forged two significant protein degradation partnerships with big pharma. On Wednesday, the U.K.-based company announced partnerships with both Bristol Myers Squibb and Merck KGaA that have a combined value of more than $2 billion.

Both big pharma companies will seek to leverage Amphista’s proprietary Eclipsys targeted protein degradation platform to develop novel protein degrading therapeutics. Targeted protein degradation (TPD) therapies are designed to remove pathogenic protein from the body in order to potentially access disease targets that have been considered “undruggable.” Amphista’s technology has been designed to develop next-generation TPD therapeutics based on advanced mechanistic insights and novel chemistry approaches that enable the development of novel protein degrading therapeutics. Rather than rely on the narrow set of ubiquitin E3 ligase-based mechanisms used in TPDs being developed by some other companies, Amphista’s approach makes use of a wider range of the body’s own innate protein degrading proteins. The company believes this overcomes the limitations of current TPD approaches and also provides the opportunity to target a wider range of disease indications.

For Amphista, the two collaborations come about a year after the company raised $53 million in an oversubscribed Series B financing round that was led by Novartis and Eli Lilly.

The deal with Merck Healthcare, a division of the larger company, is valued at more than $1 billion across three programs in oncology and immunology. The companies will work to discover and develop small molecule protein degraders for those indications.

Amphista Chief Executive Officer Nicola Thompson said the collaboration with Merck is a “significant validation” of the progress the company has made in TPD research.

Under terms of the deal with Merck, Amphista, a spinout of the University of Dundee in Scotland, will receive €39 million, about $44 million, in upfront and R&D funding. In total, across the three programs, Amphista can potentially receive €893.5 million, about $1 billion, in total payments. The company also stands to make single-digit royalties off any commercial products that result from the study.

With BMS, Amphista will receive an upfront payment of $30 million in the partnership to develop next-generation targeted protein degradation therapeutics. In the announcement, BMS and Amphista did not hint at the number of indications the partnership could involve. Amphista said BMS will receive a global exclusive license to the degraders developed under terms of the deal and will be responsible for further development and commercialization.

“Combining our expertise with Bristol Myers Squibb’s strong legacy and experience in the protein degradation space brings new promise to the potential of delivering more effective new treatment to patients seeking treatment options,” Thompson said in a statement.

Rupert Vessey, executive vice president of research and early development at BMS, expressed excitement about harnessing the Amphista TPD platform. Vessey said the company continues to build its leadership in the protein degradation space. Earlier this year, BMS and Evotec expanded a protein degradation partnership in neuroscience. BMS is harnessing Evotec’s technology to develop novel targeted protein degradation therapies for neurodegenerative diseases, including Alzheimer’s.

Under the terms of the agreement with Bristol Myers Squibb, Amphista has the potential to earn up to $1.25 billion in performance-based milestone payments.

The protein degradation space has seen significant activity in recent months. Last week, AbbVie and Plexium forged a deal to develop TPDs for neurological conditions. Germany’s Boehringer Ingelheim also recently partnered with Roivant Sciences company VantAI on protein degradation and ubiquitination. The first program will focus on a degrader combined with multiple proprietary E3 ligase platforms. Also last week, VantAI entered into protein degradation partnerships with Janssen and BluePrint Medicines. Janssen and VantAI aim to develop protein degrader drug candidates for two significant disease targets that were undisclosed, and also collaborate on the discovery and implementation of E3 ligase platforms relating to those targets. VantAI and BluePrint aim to jointly research important targets and advance up to two novel protein degrader therapies into development.

https://www.biospace.com/article/amphista-scores-two-deals-with-big-pharma-worth-over-2b/

Jazz Adds Narcolepsy Pact with Sumitomo, Sees Clear Ahead to Vision 2025

 For Jazz Pharmaceuticals, 2022 is off to a roaring start, building on its Vision 2025 plan announced earlier this year that includes a key licensing deal with Werewolf Therapeutics and another announced Wednesday with Japan’s Sumitomo Pharma Co. for a narcolepsy treatment. With its focus on neuroscience and oncology, the company is on a clear path to hitting its goal of achieving $5 billion in annual revenue by 2025.

In a late-afternoon conference call, Jazz Chief Executive Officer Bruce Cozadd said the leadership team is extremely pleased with the company’s direction since announcing the Vision 2025 plan. “In short, we’re really pleased with where the business is and where the business is going,” Cozadd told journalists and analysts on the call as the company highlighted its first quarter financial results.

For Q1, Jazz Pharma saw total revenue of $813.7 million, an increase of 34% compared to the same period of time in 2021. Those sales were powered by $612.1 million in neuroscience, driven by sales of epilepsy drug Epidiolex and $433.6 million from Xywav, a low-sodium treatment option for both cataplexy and excessive daytime sleepiness in people living with narcolepsy. Cozadd said the company has been extremely encouraged by the ongoing launch of Xywav and has seen an increase in prescribers turning to the medication. The growth potential for Xywav is expected to be about $2 billion in annual revenue.

In addition to Xywav, Cozadd pointed to the ongoing success with Rylaze, a leukemia drug approved by the U.S. Food and Drug Administration last year. Rylaze was approved for patients who have developed hypersensitivity to E. coli-derived asparaginase, an enzyme that is a common component of the chemotherapy regimen used for leukemia patients. Currently, the medication requires dosing every 48 hours but earlier this year, Jazz submitted a supplemental Biological License Application that would allow dosing on a Monday, Wednesday, Friday intramuscular dosing schedule, as well as an sBLA for intravenous administration. Both sBLAs are being reviewed by the FDA under the Real-Time Oncology Review (RTOR) program.

Additionally, the company in-licensed two assets that Robert Iannone, global head of research and development at Jazz, said offer the company exciting possibilities in areas of core interest. The first asset, brought in from Werewolf, is an engineered IFN⍺2b cytokine pro-drug that gave Jazz its first immuno-oncology program. Now known as JZP898, the compound has demonstrated anti-tumor activity in preclinical models and Iannone suggested in a previous interview that it has the potential to complement a number of currently utilized oncology treatments.

The other newly-licensed asset is Sumitomo’s DSP-0187, a potent and highly selective oral orexin-2 receptor agonist, now known as JZP441. Iannone said the experimental therapeutic has potential applications for the treatment of narcolepsy, idiopathic hypersomnia and other sleep disorders, which “further strengthens our leadership in sleep medicine.”

Cozadd added that the licensing agreements expand the company’s pipeline in core therapeutic areas and remain consistent with its strategy.

“Our three recent transactions are aligned with our broader strategy, allowing us to focus on our highest priorities, enhance our pipeline in areas of key interest in neuroscience and oncology and drive long-term shareholder value,” he said.

Another key move for Jazz this quarter was the divestiture of narcolepsy drug Sunosi to Axsome Therapeutics in March. The company sold the medication for $53 million in upfront payments plus royalties. Cozadd said the move was strategic, allows increased investment opportunities and sharpens the company’s focus on the highest strategic priorities.

On the oncology side of the house, Zepzecala (lurbinectedin), which has been approved for the treatment of small cell lung cancer, generated $59 million for the quarter, a 9% increase. Jazz said it is pleased that Zepzecala has become the “treatment of choice” in the second line for SCLC only 18 months after it was approved by the FDA. Earlier this year, Jazz enrolled the first patient in its EMERGE 201 study, which will assess Zepzecala as a monotherapy in various solid tumors. Jazz hopes that Zepzecala, an alkylating drug that binds guanine residues within DNA, will prove to be safe and effective in different solid tumor types, including urothelial carcinoma, large cell neuroendocrine carcinoma of the lung and homologous recombination deficient tumors.

Looking ahead, Jazz is anticipating data from a Phase III study of nabiximols in multiple sclerosis later this year that could lead to a New Drug Application by the end of 2022.

https://www.biospace.com/article/jazz-inks-narcolepsy-pact-with-sumitomo-sees-clear-path-ahead-for-vision-2025-/

Drug combos for obesity and Type 2 diabetes may be more effective than single therapy

 Canadian and German researchers are teaming up to identify new drug combinations to treat people with obesity and Type 2 diabetes.

The goal is to develop personalized prescriptions that are more effective than single drugs and that can potentially replace more invasive treatments such as bariatric surgery, especially for children.

"As a pediatric endocrinologist, I can tell you we're seeing more and more Type 2 diabetes in kids and adolescents, and it seems to be a more aggressive form than adult onset diabetes, so we do need better therapies to achieve even greater efficacy and degree of weight loss," said Andrea Haqq, a professor in the University of Alberta's Faculty of Medicine & Dentistry.

The researchers recently published a paper that examines the potential of several drugs that control incretins. These metabolic hormones stimulate the body to produce insulin and use it effectively. They also suppress appetite in order to control blood sugars and reduce weight.

The researchers conclude that combining the drugs has several advantages, including higher effectiveness in at least some patients and fewer side-effects.

Even a five per cent weight loss is considered clinically meaningful, and patients in some of the combination drug trials are achieving 10 or 15 per cent, said Haqq, who is a member of the Alberta Diabetes Institute and the Women and Children's Health Research Institute.

Haqq's laboratory is collaborating with that of Timo Müller, director of the Institute for Diabetes and Obesity at the Helmholtz Diabetes Center and a researcher with the German Center for Diabetes Research in Münich, Germany.

As part of the collaboration with the Müller team, first author Qiming Tan, a PhD candidate in the U of A Faculty of Medicine & Dentistry, will study for a term in Germany and a German student will join Haqq's lab here.

Haqq and Tan recommend further research to identify why some individuals respond differently to the drugs. Some racial and ethnic groups bear a disproportionate burden of obesity and Type 2 diabetes, they said, so more participants from these groups are needed in trials. Further studies should also focus on how differences in biological sex affect drug efficacy and safety.

In addition to drug combinations, the researchers are looking for non-pharmacological solutions, such as how adding fibre to a person's diet can slow weight gain and improve the effectiveness of existing diabetes medications.

---

Story Source:

Materials provided by University of Alberta. Original written by Gillian Rutherford. Note: Content may be edited for style and length.

---

Journal Reference:

1. Qiming Tan, Seun E. Akindehin, Camila E. Orsso, Richelle C. Waldner, Richard D. DiMarchi, Timo D. Müller, Andrea M. Haqq. Recent Advances in Incretin-Based Pharmacotherapies for the Treatment of Obesity and Diabetes. Frontiers in Endocrinology, 2022; 13 DOI: 10.3389/fendo.2022.838410

https://www.sciencedaily.com/releases/2022/05/220503141311.htm

For stroke survivors, modified cardiac rehabilitation can cut risk of death by 76%

 Survivors of serious stroke can reduce their chances of dying within the year by 76% if they complete a modified cardiac rehabilitation program that includes medically supervised exercise, prescribed therapy, and physician follow-up, according to new research published in the Journal of Stroke & Cerebrovascular Diseases, published by Elsevier. The findings have the potential to change the future of stroke care.

The study is the latest research from the ongoing Stroke-HEARTTM Trials at Hackensack Meridian JFK Johnson Rehabilitation Institute, located in Edison, NJ, USA. The study shows that participants in the JFK Johnson Stroke Recovery Program also significantly improved exercise capacity, mobility, self-care, and cognition.

"After a stroke, sometimes family members are cautious. 'Don't get up, you might fall.' Many caregivers of stroke survivors discourage stroke patients from being active and mobile," said Sara J. Cuccurullo, MD, Chairman and Medical Director of JFK Johnson and a Co-Principal Investigator of the study. "But we are showing that even survivors of serious stroke can exercise safely in a supervised program -- and they can benefit enormously."

The JFK Johnson Stroke Recovery Program (SRP) provides 36 sessions of medically monitored interval cardiovascular training -- as well as follow-up visits with a Physical Medicine and Rehabilitation physician along with psychological, nutritional, and educational support and risk factor (such as smoking, diet, and exercise) management. The research found that stroke patients, even those who may experience hemiplegia, can exercise safely with some modifications, such as the use of recumbent bicycles.

The research follows survivors with strokes serious enough to require inpatient hospital rehabilitation at JFK Johnson. The study so far has included more than 1,600 stroke survivors. Because stroke can vary greatly from one survivor to the next, the study created a subgroup of patients closely matched for gender, race, type of stroke, age, medical complexity, and functional scores at hospital discharge.

Of 449 patients in this subgroup, 246 completed the program. Among the patients who completed the program, four died within a year of their stroke. Among the non-participants, 14 patients died. This translates into a four-fold reduction in one-year all-cause mortality.

The researchers hope the ongoing research will persuade the Centers for Medicare & Medicaid Services (CMS) to cover comprehensive stroke rehabilitation the same way cardiac rehabilitation is covered in people who have cardiac events; both stroke and cardiac events involve the vascular system.

"Stroke survivors deserve the same benefits that patients with cardiac disease receive. As a nation, we need to do more to help patients with stroke improve their lives -- to improve both their longevity and quality of life," commented Talya Fleming, MD, Medical Director of the JFK Johnson Stroke Recovery and Aftercare Programs and Co-Principal Investigator of the study. "We should enable stroke survivors to function in the community at the highest level possible."

The study also found the Stroke Recovery Program participants improved in other ways. Participants saw a 78% increase in their cardiovascular capacity. (Many people with stroke also have cardiovascular disease.) The Stroke Recovery Program participants showed steady improvement in scores related to mobility, self-care, and communication/cognition. Research results show the matched pairs function similarly at the beginning of the study; over time, the study SRP participants perform better compared to the non-participants as they move forward with the Stroke Recovery Program.

"You see a real divergence," Dr. Cuccurullo added. "What this means to patients is that instead of just walking around the house, maybe you can walk around the block. It means you can feed and take care of yourself at a much higher level of independence. We also see speech and cognition improve. Exercise has significant and multiple benefits associated with it, including promoting overall improvement in circulation, especially promoting enhanced circulation to the brain."

The research continues. Future phases of Stroke-HEARTTM Trials will include other rehabilitation institutes as the research expands nationally.

---

Story Source:

Materials provided by Elsevier. Note: Content may be edited for style and length.

---

Journal Reference:

1. Sara J. Cuccurullo, Talya K. Fleming, Stavros Zinonos, Nora M. Cosgrove, Javier Cabrera, John B. Kostis, Christine Greiss, Arlen Razon Ray, Anne Eckert, Rosann Scarpati, Mooyeon Oh Park, Martin Gizzi, William J. Kostis. Stroke Recovery Program with Modified Cardiac Rehabilitation Improves Mortality, Functional & Cardiovascular Performance. Journal of Stroke and Cerebrovascular Diseases, 2022; 31 (5): 106322 DOI: 10.1016/j.jstrokecerebrovasdis.2022.106322

https://www.sciencedaily.com/releases/2022/05/220503141326.htm

Anti-cancer activity seen in sustained release capsaicin formulations

 A study by a team of researchers at the Marshall University Joan C. Edwards School of Medicine provides the first published in-depth description of the anti-cancer activity of capsaicin sustained release formulations. Capsaicin is naturally found in chili peppers and is the agent that provides the hot and spicy taste when eating chili peppers. Sustained release formulation of capsaicin are being explored for extended anti-cancer activity.

Recently published in Pharmacology & Therapeutics, a leading medical review journal in the field of pharmacology, the article chronicles the growth-suppressive activity of sustained release capsaicin drugs, including solid dispersion systems, liposomes, phospholipid complexes and nanoparticles. This is the first publication to provide an in-depth description of the anti-cancer activity of capsaicin sustained release formulations. The research team was led by Associate Professor of Biomedical Sciences Piyali Dasgupta, Ph.D., and Professor of Biomedical Sciences Monica Valentovic, Ph.D.

"This review article is the first to provide a comprehensive overview of capsaicin formulations in human cancer," said Dasgupta, corresponding author on the publication. "Previous publications in the literature only briefly address sustained release formulations of capsaicin."

The nutritional agent capsaicin displayed robust growth-inhibitory activity in a diverse array of human cancers. However, the clinical applications of capsaicin as a viable anti-cancer agent were hindered by three factors -- poor solubility, low bioavailability and spicy flavor.

"Oral use of capsaicin is associated with unfavorable side effects such as stomach cramps, nausea, a burning sensation in the gut and gastrointestinal irritation," said Valentovic, a senior author on the publication. "A strategy to overcome these drawbacks is the development of different delivery systems, such as encapsulating capsaicin in long-acting sustained release drug delivery systems could allow for more consistent capsaicin levels that could be more efficient as anti-cancer agents."

In addition to Dasgupta and Valentovic, clinical faculty Maria T. Tirona, M.D., Joshua Hess, M.D., and Paul Finch, M.D., contributed to the publication as well as co-authors Stephen Richbart, Justin Merritt, Ashley Cox, Emily Moles and Katie Brown.

This research was supported by the R15 Academic Research Enhancement Award Grants from the National Institutes of Health (1R15CA161491-01A1, 2R15CA161491-02, 2R15CA161491-03, R15AI151970-01 and1R15HL145573-01), the West Virginia IDeA Network of Biomedical Research Excellence (WV-INBRE) grant (P20GM103434) as well as the National Science Foundation (SURE) and West Virginia NASA State Grant Consortium.

---

Story Source:

Materials provided by Marshall University Joan C. Edwards School of Medicine. Note: Content may be edited for style and length.

---

Journal Reference:

1. Justin C. Merritt, Stephen D. Richbart, Emily G. Moles, Ashley J. Cox, Kathleen C. Brown, Sarah L. Miles, Paul T. Finch, Joshua A. Hess, Maria T. Tirona, Monica A. Valentovic, Piyali Dasgupta. Anti-cancer activity of sustained release capsaicin formulations. Pharmacology & Therapeutics, 2022; 238: 108177 DOI: 10.1016/j.pharmthera.2022.108177

https://www.sciencedaily.com/releases/2022/05/220504135629.htm

Link between Parkinson's gene and vocal issues could lead to earlier diagnosis

 Parkinson's disease is perhaps best known for its movement-related symptoms, particularly tremors and stiffness.

But the disease is also known to hinder vocal production, giving those with Parkinson's a soft monotonous voice. Those symptoms, research has suggested, often appear much earlier in the disease's development -- sometimes decades before movement-related symptoms.

New research by University of Arizona neuroscientists suggests that a specific gene commonly associated with Parkinson's may be behind those vocal-related issues -- a finding that could help lead to earlier diagnoses and treatments for Parkinson's patients.

The research was conducted in the lab of Julie E. Miller, an assistant professor of neuroscience and of speech, language, and hearing sciences in the College of Science.

"We have this big gap here -- we don't know how this disease impacts the brain regions for vocal production, and this is really an opportunity to intervene early and come up with better treatments," said Miller, who also has joint appointments in the Department of Neurology and the Graduate Interdisciplinary Program in Neuroscience, and is a member of the UArizona BIO5 Institute.

The study was published Wednesday in the scientific journal PLOS ONE. César A. Medina, a former Ph.D. student in Miller's lab who is now a postdoctoral scholar at Johns Hopkins University, is the paper's lead author. Also involved in the research were Eddie Vargas, a former UArizona undergraduate student who will soon attend the College of Medicine -- Tucson, and Stephanie Munger, a research professional in the Department of Neuroscience.

A unique, ideal model for studying human speech

To investigate any correlation between vocal changes and the Parkinson's-related gene -- known as alpha-synuclein -- the researchers turned to the zebra finch, a songbird native to Australia.

The birds are an ideal model for human speech and voice pathways for several reasons, Medina said. Young finches learn their songs from older, father-like male birds, much in the same way babies learn to speak by listening to their parents. The part of a finch's brain that deals with speech and language is also organized very similarly to its counterpart in the human brain.

"These similarities across behavior, anatomy and genetics allow us to use the zebra finches as a model for human speech and voice," Medina said.

To see how alpha-synuclein might affect vocal production in the birds, researchers first took baseline recordings of their songs. They then introduced a copy of the gene into some of the birds; other birds were not given the gene so researchers could compare the results. All the birds' songs were recorded again immediately after introducing the gene, and then one, two and three months later.

The researchers used computer software to analyze and compare the acoustic features of the songs over time, studying pitch, amplitude and duration of the songs to determine whether and when the birds' vocal production changed.

Initial findings showed that alpha-synuclein did affect song production. The birds with the gene sang less after two months, and they sang less at the start of a song session three months after receiving the gene. The vocalizations were also softer and shorter, findings similar to what is seen in the human disease.

Another step toward earlier diagnoses and treatments

To determine whether the effects on speech were connected to changes in the brain, the researchers zeroed in on a section of the brain called Area X. They found that there were higher levels of the alpha-synuclein protein in Area X, helping them establish that the gene did, in fact, cause the changes in the brain that led to changes in vocal production, Medina said.

This connection, he added, had been predicted in previous Parkinson's research, but it was not conclusive.

The next step, Miller said, is figuring out how to apply these findings to human data, which could provide more answers that lead to better Parkinson's diagnoses and treatments -- ones that come long before movement-related symptoms tell a patient to visit a neurologist.

The long-term goal of the Miller Lab, she said, is to partner with other researchers and private companies to develop drugs that target alpha-synuclein and other genes associated with Parkinson's.

Doing so, Medina said, would mean "we could stop the progression of Parkinson's disease before it becomes a detrimental impediment to the quality of life for the patient."

---

Story Source:

Materials provided by University of Arizona. Original written by Kyle Mittan. Note: Content may be edited for style and length.

---

Journal Reference:

1. Cesar A. Medina, Eddie Vargas, Stephanie J. Munger, Julie E. Miller. Vocal changes in a zebra finch model of Parkinson’s disease characterized by alpha-synuclein overexpression in the song-dedicated anterior forebrain pathway. PLOS ONE, 2022; 17 (5): e0265604 DOI: 10.1371/journal.pone.0265604

https://www.sciencedaily.com/releases/2022/05/220504144523.htm

Benefits of exercise may vary greatly in primary mitochondrial disease

 Mitochondria serve as the main source of energy production in our cells, and endurance exercise is generally known to improve the function of mitochondria. However, the benefits of exercise in patients with primary mitochondrial diseases, which are heterogeneous and caused by a variety of genetic mutations, were largely unknown.

In a new study, researchers at Children's Hospital of Philadelphia (CHOP) demonstrated that the benefits of endurance exercise can vary based on the type of mutation involved in mitochondrial disease, and while the benefits of exercise outweigh the risks, the mitochondrial genetic status of patients should be taken into consideration when recommending exercise as therapy. The findings were published online today by the Proceedings of the National Academy of Sciences.

Primary mitochondrial diseases represent the most prevalent inherited metabolic disorders, affecting approximately 1 in every 4,200 people. These disorders can be caused by hundreds of different mutations in the nuclear DNA (DNA within our cells) or mitochondrial DNA (mtDNA, or the DNA within the mitochondria within our cells). Universal treatments for these patients are limited. However, endurance exercise has been shown to improve mitochondrial function in healthy people and reduce the risk of developing secondary metabolic disorders like diabetes or neurodegenerative diorders.

However, these recommendations were based on healthy people without primary mitochondrial disease. Therefore, researchers wanted to determine effectiveness for these patients and whether they are actually benefitting from endurance exercise.

"There was not a concensus among clinicians who see patients with mitochondrial disease whether endurance exercise truly offers benefits," said Patrick Schaefer, PhD, a postdoctoral fellow at the Center for Mitochondrial and Epigenomic Medicine at CHOP and first author of the study. "Exercise helps create more mitochondria, but if those mitochondria still have the mutations associated with primary mitochondrial disease, there is a chance that exercise may put some patients at risk."

Because of the heterogeneity of primary mitochondrial disease among patients, the researchers used animal models to study five mutations responsible for the disease. The goal of the study was to determine the relationship between mitochondrial mutations, endurance exercise response, and the underlying molecular pathways in these models with distinct mitochondrial mutations.

The study found that endurance exercise had different impacts on the models depending on the mutation involved. Exercise improved response in the model with the mtDNA ND6 mutation in complex I. The model with a CO1 mutation affecting complex IV showed significantly fewer positive effects related to exercise, and the model with a ND5 complex 1 mutation did not respond to exercise at all. In the model that was deficient in nuclear DNA Ant1, endurance exercise actually worsened cardiomyopathy.

Additionally, the researchers were able to correlate the gene expression profile of skeletal muscle and heart in the model with exercise response and identified oxidative phosphorylation, amino acid metabolism, and cell cycle regulation as key pathways in exercise response, suggesting how the model might be adapted to study exercise responses in humans with primary mitochondrial disease.

Despite mixed responses of the models used in this study, the authors note that the benefits of exercise outweigh the risks in most cases. However, the physical and mitochondrial status of the patient should be taken into account when recommending therapeutic exercises. Additionally, the study could help researchers identify biomarkers and pathways to help predict the mitochondrial response to exercise both in mitochondrial patients and the healthy population harboring different mitochondrial haplogroups.

"This work is of fundamental importance in demonstrating that individuals with different mitochondrial bioenergetics will respond differently to endurance exercise," said senior study author Douglas C. Wallace, PhD, director of the Center for Mitochondrial and Epigenomic Medicine at CHOP and the Michael and Charles Barnett Endowed Chair in Pediatric Mitochondrial Medicine and Metabolic Diseases. "This is of broad relevance to individuals ranging from athletes to patients with mitochondrial disease, and everyone in between."

This study was supported by the German Research Foundation through grant SCHA 2182/1-1, the National Institutes of Health grants NS021328, MH108592, and OD010944, and U.S. Department of Defense grants W81XWH16-1-0401 and W81XWH-21-1-0128. Schematics were created with BioRender.com.

---

Story Source:

Materials provided by Children's Hospital of Philadelphia. Note: Content may be edited for style and length.

---

Journal Reference:

1. Patrick M. Schaefer, Komal Rathi, Arrienne Butic, Wendy Tan, Katherine Mitchell, Douglas C. Wallace. Mitochondrial mutations alter endurance exercise response and determinants in mice. Proceedings of the National Academy of Sciences, 2022; 119 (18) DOI: 10.1073/pnas.2200549119

https://www.sciencedaily.com/releases/2022/05/220504110430.htm