Compounds Used In The Treatment of Mitochondrial Diseases (RDLP# 608)

It is estimated that 70,000 individuals in the U.S. suffer from a mitochondrial disease. The majority of children with a mitochondrial disease of genetic origin suffer considerable morbidity and mortality before the age of five. The common factor among these diseases is that the mitochondria are unable to convert food and oxygen into energy. If food and oxygen are not completely converted to energy, both accumulate in the body and become toxic.

Current therapies include vitamin or enzyme therapy, and while some improvement can be seen by a change in diet, this approach does not significantly alter the progression of the disease.

The inventors have discovered four compounds, which can effectively raise the level of enzyme complexes of the mitochondrial respiratory chain in tissue culture cells. This suggests that these compounds are working to maintain the conversion of food and oxygen to energy. These four compounds have been shown to elevate this activity 12-24% above control values, a very promising result.

Therapeutic use of these compounds for the treatment of mitochondrial disease is novel. All four compounds are disclosed in the prior art, but none have been used in the study of mitochondrial diseases. Both Captopril and Veratrine are FDA approved drugs; they are angiotensin converting enzyme inhibitors that relax the arteries and lower blood pressure. They are currently provided to individuals suffering from hypertension. Betulin and ursolic acid are both naturally occurring compounds known to have medicinal properties.

pre-clinical in vivo validation

Inventors: Dr. Brian H. Robinson and Dr. Mary Maj