(Seattle, WA) The United Mitochondrial Disease Foundation awarded $500,000 in research grants to projects designed to bring faster treatments and cures for mitochondrial disease patients. The grant awards were presented at the UMDF’s Mitochondrial Medicine 2016: Seattle symposium.
The following grants were presented by the UMDF following the recommendation by the grant review committee.
Brendan J. Battersby, Ph.D., Research Director
Biomedicum Helsinki, Research Programs Unit-Molecular Neurology, University of Helsinki (Finland),
Investigating the Pathogenesis of C12orf65 Deficiency in Mitochondrial Translation and Mitochondrial Disease
Principal Investigator Award, 2 years/$70,000
The goal of this research project led by Dr. Battersby is to address a significant gap in mechanistic knowledge within the mitochondrial field- ribosome function and translation. The outcome of this work could provide unique insights into the broad range of mitochondrial disease symptoms that result from mutations in the C12orf65 gene.
Alessandro Bitto, Ph.D.,
Department of Pathology, University of Washington Medical Center (USA)
Molecular Mechanisms for Suppression of Mitochondrial Disease by Acarbose, Postdoctoral Fellowship Award, 2 years/$70,000
Dr. Bitto, under the mentorship of Dr. Matt Kaeberlein, will evaluate an FDA-approved drug called acarbose for efficacy in a translational mouse model of Leigh Syndrome. The drug impacts mTOR signaling, an important mitochondrial function pathway whose understanding could open up a broad therapeutic strategy for mitochondrial disease.
Nicola Brunetti-Pierri, MD, FACMG, Associate Investigator, Telethon Institute of Genetics and Medicine (Italy), Phenylbutyrate Therapy for Pyruvate Dehydrogenase Deficiency, Small Clinical Study Award,
This grant, winner of the 2016 Chairman’s Award for highest rated research proposal after peer review, is a clinical study of a new potential therapy for pyruvate dehydrogenase complex (PDHC) deficiency by lowering lactate levels. This project comes 5 years after Dr. Brunetti-Pierri received a UMDF grant to first test phenylbutarate on patient cells. Subsequent animal model studies confirmed the promising in vitro data that resulted from the first grant, and now a pilot clinical trial will be carried out across multiple centers in Italy. Positive results from the pilot study would lead to a larger study directed toward PDHC deficiency patients.
Adam Hughes, Ph.D.
Assistant Professor of Biochemistry, University of Utah School of Medicine (USA), Quality Control of Unimported Mitochondrial Precursor Proteins, Principal Investigator Award
Utilizing yeast models, Dr. Hughes intends to explore the link between loss of mitochondrial membrane potential and mis-targeted mitochondrial proteins. That the accumulation of such proteins and their associated “waste disposal” is a source of mitochondrial pathology is a novel and intriguing premise that could open up many new avenues in future research.
Leo Nijtmans, Ph.D.
Radboud University Medical Centre, Nijmegen (Netherlands),Mitochondrial Complexome Profiling Provides a Novel Tool to Diagnose and Understand Complex I Deficiency, Principal Investigator Award, 1 year/$40,000
Complex I disorders are some of the most common types of mitochondrial disease. Dr. Nijtmans will utilize a profiling technique to study protein interactions within Complex I using patient cell lines. The results will provide insight into Complex I assembly and function, and could ultimately lead to new therapeutic targets for investigation.
George A. Porter, Jr., MD, Ph.D.
Assistant Professor, Department of Pediatrics, Division of Cardiology, University of Rochester Medical Center (USA), Manipulating the Permeability Transition Pore to Ameliorate Neonatal Heart Failure, Principal Investigator Award
Many types of mitochondrial disease have associated cardiomyopathies. In this translational research project Dr. Porter will test potential therapies for cardiomyopathies in a mouse model. Success in this project would initially open the possibility for treating neonates with bioenergetics disorders, and eventually have potential for more broadly treating mitochondrial disease patients with Complex I disorders.
Eric A. Shoubridge, Ph.D.
Professor and Chair, Department of Human Genetics, Montreal Neurological Institute, McGill University (Canada), Interrogating the Mitochondrial Interactome Using BioID, Principal Investigator Award
Dr. Shoubridge’s project will identify functional networks within the mitochondria based on the analysis of protein-protein interactions. In addition to the potential for revealing new insights into mitochondrial disease, the availability of a mitochondrial protein interactome will be a generally useful resource for addressing basic questions regarding mitochondrial structure and function in both a normal and diseased state.
Zarazuela Zolkipli Cunningham, MBChB MRCP
Division of Neurology,The Children’s Hospital of Philadelphia (USA),Development and Validation of a New Outcome Measure in Mitochondrial Disease, Small Clinical Study Award
Dr. Zolkipli Cunningham and collaborators aim to develop a new outcome measure for mitochondrial myopathy that is specifically designed for use in Phase II/III clinical trials. The patient perspective will be critical to the project, helping to ensure that meaningful measures are developed over the full range of disease state- from early ambulatory to late non-ambulatory. Recognizing the urgent need for improved clinical trial endpoints, the development of this scale will build upon existing scales and tools.