News Feature | April 2, 2014

Research Highlights Potential Drug Target For Mitochondrial Diseases

By Marcus Johnson

Researchers at the Whitehead Institute and Massachusetts Institute of Technology are working on developing new treatments for mitochondrial diseases. The medical community has long struggled to treat mitochondrial disorders, and new research has generated optimism that experts would be able to rehabilitate cells suffering from mitochondrial dysfunction. Mitochondrial diseases can be debilitating or even fatal, as they affect the cell's ability to generate power. David Sabatini, who led the research, said that mitochondrial diseases can lead to a broad range of negative effects for patients. “With mitochondrial diseases, there are a variety of different outcomes, but there is consistency in terms of muscle degeneration, metabolic changes in the blood, drop in blood pH, and neuronal effects. But really all tissues can be affected,” said Sabatini.

The researchers first gave cells the small molecule drug antimycin, which suppressed mitochondrial function. It was then the researchers were able to find that cells with mutations rendering the ATPIF1 gene inactive were able to resist dangerous mitochondrial toxins, often preventing the death of the cell. Researchers concluded that suppressing the ATPIF1 gene would generate more positive outcomes for patients with mitochondrial diseases.

However, Sabatini claimed that future treatments could be difficult. “ATPIF1 – while its loss does not seem to be overtly toxic to the cell, theoretically making it a good drug candidate – the problem is this protein coded by this gene is not a traditional drug target. So making a small molecule inhibitor of this will be challenging,” said Sabatini. “The question is: How would you interfere with the function of this gene in an animal or a person, when it’s not druggable in a traditional sense? But then again, what chemists consider druggable is constantly changing.”