Mitochondrial Myopathy Clinical Trial teleconference
12/6/2016 teleconference discussion of data from Stealth BioTherapeutics’ Mitochondrial Myopathy clinical trial.
This summer, Stealth BioTherapeutics (Stealth BT) shared preliminary positive data from the MMPOWER study. The study purpose was to evaluate safety and efficacy of elamipretide (previously known as Bendavia) in adults with primary mitochondrial myopathy and genetically confirmed mitochondrial disease.
Mitochondrial myopathy is primarily characterized by muscle weakness, fatigue, and exercise intolerance. Patients with genetically confirmed mitochondrial disorders may also experience multi-system organ involvement and myriad complications related to the body’s inability to adequately generate energy (ATP) at the cellular level. The MMPOWER trial measured changes in the participant’s ability to complete a Six-Minute Walk Rest, a performance-based measure of functional exercise capacity.
This collaborative presentation is hosted by MitoAction, the United Mitochondrial Disease Foundation, the Foundation for Mitochondrial Medicine, with Stealth BT to learn more about the results from the MMPOWER trial, and information about the planned Phase 3 clinical trial. This special presentation educates and informs patients, parents, caregivers, family members, and others involved in the daily lives of adults and children with mitochondrial disease.
Teleconference led by Stealth BT’s CEO, Reenie McCarthy. “As a leader in mitochondrial medicine, we are committed to developing innovative therapies for rare mitochondrial diseases, as well as for common diseases of aging in which impaired mitochondrial function is a final common pathway,” she says.
Teleconference/webinar offered in collaboration by UMDF, MitoAction.
Mitochondrial Disease Profiled at Annual Bio Convention
FMM’s Executive Director, Laura Stanley, Participated in the BIO 2016 International Conference in San Francisco
San Francisco was the city. The BIO 2016 International Convention www.bio.org was the place. Mitochondrial Disease was in the spotlight among 15,000 biotechnology and pharma leaders who came together for one week of intensive networking to discover new opportunities and promising partnerships. This event covered a wide spectrum of life science and application areas including drug discovery, biomanufacturing, genomics, biofuels, nanotechnology and cell therapy. It was both exciting and gratifying to seeMitochondrial Disease as a key topic during the convention’s breakout sessions.
The UMDF’s Phil Yeske and Liz Kennerley and I were key patient advocacy voices along with scientific experts like Drs. Michio Hirano, Marni Falk, Mark Tarnopolsky, Hani Sabbah and pharma representatives from Stealth Biotherapeutics, Edison Pharmaceuticals along with several others holding a strong interest in mitochondrial dysfunction, like Raptor, Avanex, Reata, Retrotrope, Cardero Therapeutics and more. Three different sessions highlighted 1) the challenges and opportunities in mitochondrial disease research, 2) scientific regulatory gaps for drug development and 3) the promise of mitochondrial research to unlock answers of aging and other diseases like Parkinson’s and Alzheimer’s. Each session boasted a full room of attendees and the audience participation demonstrated the increasing level of prominence and emphasis of mitochondrial research in the biotech community.
A noteworthy highlight included Stealth Biotherapeutics announcing promising results of their recent mitochondrial myopathy clinical trial of the drug Ilamipretide. See details in the attached press release. http://www.prnewswire.com/news-releases/stealth-biotherapeutics-reports-positive-elamipretide-data-in-first-of-its-kind-primary-mitochondrial-myopathy-trial-300286373.html?tc=eml_cleartime Additionally, the complexities of clinical trial design, endpoints and participation were presented—plenty of reminders that getting drugs to market is a long, hard road. We patients are definitely a voice for positive change and there is momentum. It is my hope that our community continues to gain traction and that through partnerships and collaboration like those fostered at Bio, treatments can be attained for our patients and for multiple diseases. Hope can fly. Hope can heal. Please continue to share stories, fuel connections and help fund treatments.
Click Below to View Laura’s Presentation
Research Updates – Foundation for Mitochondrial Medicine
Progress from two key FMM funded research projects continue to emphasize the important role mitochondria and mitochondrial dysfunction play in many neurodegenerative diseases.
Mitochondria-Targeted Therapeutic Discovery Project to Treat Parkinson’s and Mitochondrial Disease
The FMM-Michael J. Fox Foundation co-funded research project led by Dr. Wolfdieter Springer from the Mayo Clinic Jacksonville shows promising results. Mutations in the gene for parkin are a common cause of early-onset Parkinson’s disease. Research into the biology of parkin has revealed an important role for the protein in maintaining healthy mitochondria. This has led to great interest in developing drugs that can activate parkin as a way to rescue cells from disease mechanisms that impair the normal regulation of mitochondria. In 2013, these efforts were given a major boost when several independent laboratories determined the structure of the parkin protein which led to greater understanding of how to design drugs that can target it. The schematic below is a representation of this structure. Researchers believe that drugs that target the ‘Ubl’ region may be able to activate the protein and allow it to help cells get rid of dysfunctional, unhealthy mitochondria.
Using the knowledge gleaned from the structure of the parkin protein, Dr. Springer is designing drug compounds that he believes can activate the protein. Dr. Springer presented initial results of his efforts and he has shown that a number of the drug compounds he designed appear to activate parkin and allow it to target mitochondria. As a next step, he will further optimize the compounds and also test whether they can rescue damaged mitochondria in laboratory models, a key step before deciding whether to move the compounds into further testing for Parkinson’s disease and mitochondrial disease.
Dr. Springer has also established several important collaborations with other key investigators working on parkin. These joint efforts should allow him to test additional compounds as well as gain access to other laboratory tests of parkin activity that will further strengthen his findings.
Novel Research for Mitochondrial-Directed Therapies to Address Alzheimer’s and Mitochondrial Disease
FMM and the Alzheimer’s Drug Discovery Foundation awarded a $200,000 grant to Dr. James Bennett of Virginia Commonwealth University. The purpose of this study is to determine if boosting mitochondrina function in mice engineered to develop aspects of Alzheimer’s disease will improve their memory and cognitive function. For these studies, Dr. Bennett is using a therapy that is in development by the biotechnology company, Gencia. This therapy, called rhTFAM, can be injected intravenously, and helps to stimulate the generation of new mitochondria, referred to as “mitochondria biogenesis.”
Dr. Bennett found that the rhTFAM treatment improved memory retention in the Alzheimer’s mice. Dr. Bennett and team are presently analyzing the brains of the rhTFAM-treated mice to look for effects on Alzheimer’s pathology and improvements in mitochondrial respiration and function. These positive initial finding on improving memory in mice have generated excitement about the potential of this therapy for Alzeimer’s patients as well as for other indications that exhibit mitochondria dysfunction. Often in mitochondrial disease, cognitive fatigue and impairments are some of the many symptoms patients exhibit. Gencia is enthusiastic about accelerating the development of rhTFAM into patient populations through clincial trials. The translational nature of Dr. Bennett’s research could have critical applications beyond Alzheimer’s disease to other related disorders that affect millions of Americans.
Fund The Cures – Support FMM!
The Foundation for Mitochondrial Medicine is dedicated to supporting the most promising treatments for the many forms of mitochondrial disease.
We support treatment based research, Institutional Review Board IRB-approved and/or FDA-approved studies. We are the first mitochondrial disease non-profit organization to have financially supported the first FDA-approved drug treatments, begun in 2009. In addition to functional MRI brain studies on cognitive fatigue, our grants are allowing new drug compounds to be tested, eventually leading to full clinical drug trials. Your support means momentum to accelerate entry into clinical trial phases, which will in turn propel research faster toward the cures.
One cure, one timeline, simply does not exist but with your help we will move forward faster.
Examples of FMM Research Grants:
- 2014: $175,000 Mitochondrial-targeted Therapeutic Project with the Michael J. Fox Foundation awarded to Dr. Deitrich Springer, Mayo Clinic Jacksonville, FL
- 2013: $200,000 Mitochondrial Drug Discovery Project with the Alzheimer’s Drug Discovery Foundation, awarded to Dr. James Bennett, Virginia Commonwealth University
- 2012: 10 Patients Funded for fMRI Trial at Georgia Tech and Georgia State University, Atlanta, GA
- 2011: $50,000 Grant to Netherlands Research Team
- 2010: Support of FDA Clinical Trial – EP1-743
Researchers Fight for Alzheimer’s Cure
Alzheimer’s disease is the nation’s sixth leading cause of death and is predicted to affect 15 million elderly Americans by 2050.
Charles DeCarli is a neurologist and Alzheimer’s Disease Center director at UC Davis. Their clinic sees both patients and research study participants. They use a wide variety of treatments to attempt to stymie the damage this disease causes to the brain. The damage Alzheimer’s disease causes to the brain are startling.
According to Alz.org, brain atrophy is a prominent symptom in those affect. Parts of the brain that deal with memory and thought formation shrink, while fluid-filled spaces of the brain become larger.
DeCarli prescribes medications like Aricept and Nemenda, medications specifically geared to slowly memory loss in dementia associated with Alzheimer’s disease. However, the clinic is focusing on alternative methods of treatment to slow memory loss. Their clinic offers classes like Brain Fitness 101 to offer treatments emphasizing a healthy diet and brain exercises that can only postpone the decline in cognition.
The recent recession caused California, already the nation’s leader in researching Alzheimer’s disease, to cut funding to centers like the one DeCarli works. Despite the fact Alzheimer’s disease or other forms of dementia affect 1 in 3 seniors funding for this disease pales in comparison to diseases like cancer. Cancer researchers receive about $5 billion by the federal government each year, while Alzheimer’s researchers receive about $560 million.
DeCarli evaluates the research participants on a monthly basis, attempting to identify patterns in his patients’ deterioration. One of the more difficult parts of dealing with Alzheimer’s is noting the stages it attacks the brain. Working against a limited budget and time, his clinic uses autopsies of patients in an attempt to make sense of the way it affects research participants.
Alzheimer’s research is still greatly underfunded. You can make a difference by donating today.
What is the role of mitochondrial dysfunction in Alzheimer’s disease?
Mitochondrial dysfunction has surfaced as one of the most discussed hypotheses associated with the etiology and underlying disease components of Alzheimer’s disease.2 Mitochondria assume central functions in the cell, including ATP production, calcium homeostasis, reactive oxygen species generation, and apoptotic signaling. Although their role in the cause of Alzheimer’s disease may be controversial, there is no doubt that mitochondrial dysfunction, abnormal mitochondrial dynamics and degradation by mitophagy occur during the disease process, contributing to the onset and progression of Alzheimer’s disease.
Research Indicated that Parkinson’s Disease Makes Mitochondria Dysfunctional
Neuroscientists Vanessa Moraïs and Bart de Strooper have recently discovered molecular pathways affecting the development of Parkinson’s disease. Their research indicated that Parkinson’s disease makes mitochondria, organelles responsibly for the energy production of the cell, dysfunctional.
There are six complexes in mitochondria which synthesize energy for cells. Moraïs and Strooper have identified the gene Pink1 in the first complex of mitochondria. A mutation in this gene is responsible for decreased energy production in the mitochondria.
Model organizations such as fruit flies and mice have confirmed the link between this gene, mitochondrial dysfunction, and Parkinson’s disease. Moraïs and Strooper were discovered that the presence of this gene in these organisms led to the ADP molecule not being phosphorylated properly. Enzymes in the mitochondrial energy production process create ATP from the ADP molecule and phosphate group. This disruption in the energy process as a result of a mutation in Pink1 led to the development of Parkinson’s disease in these organisms.
A possible treatment for patients with the Pink1 mutation involves repairing the phosphorylation of Complex 1. Continued research and clinical trials on patients will reveal if this process can slow down or cure Parkinson’s. Their research is an incredible step forward in both mitochondrial and Parkinson’s disease research and provides hope to patients who currently have limited resources for treatments to slow the progression of both diseases.
Read the article New discoveries place lack of energy at the basis of Parkinson’s disease.
To learn more about the relationship between Parkinson’s disease and mitochondrial dysfunction, CLICK HERE.
Mitochondrial disease can look like a number of better known diseases: Autism, Parkinson’s, Alzheimer’s, Lou Gehrig’s disease (ALS), muscular dystrophy and chronic fatigue, among others. And it’s this web of complexity and connectivity that makes mitochondrial disease research valuable to so many. Research shows that mitochondrial dysfunction is often at the crux of these more commonly recognized diseases. Visit www.hopeflies.org to learn more about mitochondrial disease.