Salk news: gene therapy for Lou Gehrig...( sor of neuroscience and director of the...)

Gage and his colleagues found that delivery of a non-toxic gene therapy, using an adeno-associated virus that carried IGF-1 into muscle (with subsequent transfer of IGF-1 to neurons dying in ALS), delayed disease onset by 31 days and expanded the mice's life span to a maximum of 265 days, compared to 140 days for the untreated mice. IGF-1 was also able to extend life spans by 22 days when injected after symptoms appeared, indicating the method's potential treatment for different stages of disease. In addition to extending survival, treatment with the gene therapy maintained physical movement for a significantly longer time than in untreated mice and provided 20 percent more muscle mass.

The researchers demonstrated that IGF-1 triggers a molecular pathway that appears to preserve motor nerve function. When the receptor for IGF-1 is activated, an enzyme called Akt has a phosphate molecule added to it (a process called phosphorylation). The Akt enzyme is activated and helps block the process of apoptosis, or programmed cell death.

"IGF-1 has been known to increase the number of phosphorylated Akt molecules, which inhibits apoptosis by directly inhibiting different pro-apoptotic signals," said Gage. "We found that IGF-1 decreased levels of a specific protein involved in apoptosis by more than 63 percent compared to untreated mice. Understanding this pathway led us to experiment with IGF-1 in the first place, and underscores the vital importance of understanding the fundamental mechanisms of cellular function to medical advances."

While this research is still in the experimental animal stage and a number of steps need to b
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Contact: Andrew Porterfield
porterfield@salk.edu
858-453-4100 x1340
Salk Institute
7-Aug-2003