Mitochondrial Disease Research
Children's Hospital of Philadelphia (CHOP) is a powerful hub for research on mitochondria, the power plants of the cell. Efforts in the Center for Mitochondrial and Epigenomic Medicine, Mitochondrial Medicine, and across other collaborating specialties are converging on deeper understanding of how energy production in mitochondria relates to a wide range of diseases and conditions, as well as new approaches to treating conditions known to be connected to mitochondria. Among the highlights:
- Researchers from CHOP have discovered functions or possible impairments of mitochondria in the brain related to normal brain functioning, recovery from injury and neuropsychiatric disease.
- A CHOP expert weighed in on ethical considerations for new reproductive technologies to prevent inheritance of mitochondrial diseases and took part in national and international efforts to speed the development of new therapies for these diseases.
- Douglas C. Wallace, PhD, a mitochondrial medicine pioneer, received a prestigious honor shared with such luminaries as Albert Einstein, Louis Pasteur and Benjamin Franklin and was inducted into the Italian Academy of Sciences.
- Cancer biologists have been pursuing the hypothesis that mitochondria could be part of the mechanism by which cancer resists therapies.
- CHOP researchers continue to investigate a mystery surrounding mitochondrial proteins and cellular stress responses.
- Marni Falk, MD, Executive Director of the program, discusses Examining Special Nutritional Requirements in Disease States at a workshop.
If mitochondrial disease is suspected to be the underlying cause of your or your child’s medical concerns, you will have the opportunity to participate in various ongoing research studies at Children’s Hospital of Philadelphia. Researchers are currently working on identifying better ways to diagnose and treat mitochondrial disease, identifying new genetic causes of mitochondrial disease and characterizing exactly how mitochondrial disease affects the body. Marni Falk, MD leads the Mitochondrial Research Affinity Group, bringing together researchers engaged in mitochondria-focused research.
In addition, the Center of Mitochondrial and Epigenomic Medicine (CMEM) was established as a Center of Emphasis in 2010. The center is investigating mitochondrial and epigenomic dysfunction for which few effective clinical treatments currently exist.
View our latest abstracts presented at UMDF Symposium 2022.
Current research studies
Metabolic Consequences of Primary Mitochondrial Disease
The purpose of this research study is to identify the causes and effects mitochondrial disease has on the body and to find ways to better diagnose mitochondrial disease.
Currently, there is no single laboratory test that is able to accurately diagnose mitochondrial disease in most people, and no effective treatments exist for many individuals with mitochondrial disease. Identifying the effects of mitochondrial disease on body tissues such as blood and skin may offer the opportunity for improved diagnosis and treatment.
North American Mitochondrial Disease Consortium Patient Registry and Biorepository
The main purpose of this research study is to collect and store information about people with mitochondrial diseases to better understand the underlying causes and natural history of these diseases, as well as to develop new treatment options.
This study is being organized by the North American Mitochondrial Disease Consortium (NAMDC). The NAMDC is a group of doctors and researchers in North America who specialize in mitochondrial disease. Children’s Hospital of Philadelphia is a NAMDC site.
We hope that the information and samples in the NAMDC patient registry, and repository will help researchers learn more about mitochondrial disease and find the causes and treatments for these conditions.
Magnetic Resonance Imaging (MRI) Muscle Phenotyping in Mitochondrial Disease
The purpose of the study is to use a new, non-invasive research imaging technique, which is a kind of MRI, to measure important metabolic features of muscle, including mitochondrial function, in people with mitochondrial disease and in healthy individuals.
It is hoped that this new strategy will help physicians to understand better the health problems of people with mitochondrial disease. Eventually, this could lead to better diagnostic and treatment approaches.
The Center of Mitochondrial and Epigenomic Medicine (CMEM)
CMEM was established as a Center of Emphasis in 2010. The Center is investigating mitochondrial and epigenomic dysfunction in a wide range of clinical problems. One focus of the CMEM team is on preclinical studies relevant to developing therapies for mitochondrial dysfunction, for which few effective clinical treatments currently exist.
Glycemic Index in Mitochondrial Disease
The investigators are conducting a research study on nutrition in mitochondrial disease to understand the effects of different kinds of carbohydrates that people eat. Carbohydrates are an important source of energy. Certain kinds of carbohydrates tend to raise blood sugar more in healthy people, while others tend to raise blood sugar less in healthy people.
The investigators would like to know if by eating the "right" type of carbohydrate, people with mitochondrial disease can avoid high lactate levels, high blood sugar levels, and, later, low blood sugars. In this study, this question will be answered by finding out how people with mitochondrial disease respond to two different test meals that contain different kinds of carbohydrates.
Future of research
More research efforts are being placed in mitochondrial disease here at CHOP, such as drug therapy research and soon-to-be announced clinical research treatment trials. Our clinical and research teams meet at monthly seminars to share the exciting research being conducted in mitochondrial disease at Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, as well as other institutions locally and worldwide.
Mitochondrial research publications
Ganetzky RD, Falk MJ. 8-year retrospective analysis of intravenous arginine therapy for acute metabolic strokes in pediatric mitochondrial disease. Mol Genet Metab. 2018 Mar;123(3):301-308. doi: 10.1016/j.ymgme.2018.01.010. Epub 2018 Feb 2.
Barca E, Ganetzky RD, Potluri P, Juanola-Falgarona M, Gai X, Li D, Jalas C, Hirsch Y, Emmanuele V, Tadesse S, Ziosi M, Akman HO, Chung WK, Tanji K, McCormick E, Place E, Consugar M, Pierce EA, Hakonarson H, Wallace DC, Hirano M, Falk MJ. USMG5 Ashkenazi Jewish founder mutation impairs mitochondrial complex V dimerization and ATP synthesis. Hum Mol Genet. 2018 Jun 18. doi: 10.1093/hmg/ddy231. [Epub ahead of print]
McCormick EM, Zolkipli-Cunningham Z, Falk MJ. Mitochondrial disease genetics update: recent insights into the molecular diagnosis and expanding phenotype of primary mitochondrial disease. Curr Opin Pediatr. 2018 Sep 7.[Epub ahead of print]
Muraresku CC, McCormick EM, Falk MJ. "Mitochondrial Disease: Advances in Clinical Diagnosis, Management, Therapeutic Development, and Preventative Strategies. Current Genetic Medicine Reports. 2018 May.
Kuszak AJ, Espey MG, Falk MJ, Holmbeck MA, Manfredi G, Shadel GS, Vernon HJ, Zolkipli-Cunningham Z. Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems. Annu Rev Pathol. 2017 Nov 3. doi: 10.1146/annurev-pathol-020117-043644. [Epub ahead of print]
Zolkipli-Cunningham Z, Falk MJ. Clinical effects of chemical exposures on mitochondrial function. Toxicology. 2017 Nov 1;391:90-99. doi: 10.1016/j.tox.2017.07.009. Epub 2017 Jul 27.
Kwon YJ, Guha S, Tuluc F, Falk MJ. High-throughput BioSorter quantification of relative mitochondrial content and membrane potential in living Caenorhabditis elegans. Mitochondrion. 2017 Oct 3. pii: S1567-7249(17)30030-2. doi: 10.1016/j.mito.2017.09.004. [Epub ahead of print]