Mitochondria have been linked to human disease only since the 1960s, and much of what we know about mitochondrial disorders has been discovered only in the past 20 years. Our knowledge about mitochondrial diseases is changing rapidly, as are the available tests and treatments.
Research in the Mitochondrial Program is focused on understanding the different symptom patterns in children with mitochondrial disorders and the efficacy of therapy with different medications and vitamins/supplements.
We are one of the few institutions in the United States to offer an experimental medication, dichloroacetate (DCA), to patients whose mitochondrial disease has caused lactic acidosis, a condition in which there is too much lactate in the blood and spinal fluid. This medicine has been proven to reduce the lactate levels and potentially alleviate disease symptoms.
Boston Children’s is also participating in a Phase 3 multicenter trial of DCA for pyruvate dehydrogenase deficiency, a type of mitochondrial disorder in which buildup of lactate leads to neurologic problems.
Mitochondrial disorders are genetic, though the mutations don’t always run in families. In collaboration with Pankaj Agrawal, MD, from the Manton Center for Orphan Disease Research, we are seeking to identify novel (previously unknown) mutations that cause mitochondrial disease in humans.
Stem cell models
Basic science researchers at Boston Children’s are seeking to understand how the genetic mutations that cause different mitochondrial disorders lead to disease, with the ultimate hope of finding new treatments.
In collaboration with the Harvard Stem Cell Institute and the Wyss Institute, one team is using induced pluripotent stem cells (iPS cells) created from patients with Barth syndrome, a mitochondrial disorder affecting the heart, to build a “heart on a chip.” This model may help reveal how the mutation that causes Barth syndrome weakens heart muscle. Another team, from the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, is using iPS cells to model Pearson marrow pancreas syndrome, an extremely rare mitochondrial disorder that impairs the development of blood-forming cells in the bone marrow, causing severe anemia.