Friedreich’s ataxia, a rare disease caused by the mutations in the gene for the protein frataxin, can cause both cardiac and neuromuscular complications, Wilson said. Addressing both in a single shot, as Astellas and several other companies had tried to do, turned out to be an “incredibly complicated problem” because of challenges in distribution, expression levels and therapeutic window, he said.
Frataxin, as Wilson put it, is “one of those Goldilocks proteins” — either having too much or too little would be dangerous. With ASP2016, which targets the cardiac complications of the condition, Astellas employed a mild promoter so that the AAV8-delivered gene therapy produces “just enough” protein in the target tissue.
“Our intention really has been to try and get as many cardiomyocytes transduced as we can, but not to produce such an overwhelming amount of frataxin protein that it would produce toxicity".
The company is hoping to dose the first patient in the second half of 2024.