Critical Protein Measurement Means Progress Toward Antisense Trial in ALS

June 15, 2015

Researchers funded by The ALS Association have for first time determined a critical parameter called the half-life for a disease-causing protein. This information will be crucial in the design and interpretation of therapeutic trials to reduce the levels of the protein.

Mutations in the gene for the protein, called superoxide dismutase 1 (SOD1), are the second most common cause of inherited forms of ALS. A treatment approach called antisense therapy has recently emerged as a highly promising strategy to reducing the amount of mutant SOD1 protein in people with this form of the disease. In order to proceed, however, researchers must know how quickly the protein is broken down in the body. The rate of breakdown is called the half-life (more specifically, the half-life is the time it takes for one half of any quantity of the protein to break down). The research was led by Timothy Miller, M.D., Ph.D., and Randall Bateman, M.D., and conducted by Matthew Crisp, all of Washington University in Saint Louis, MO.

The team found the half-life of the normal protein in rat cerebrospinal fluid (CSF) was 16 days, and in human CSF about 25 days, a relatively slow turnover rate in the nervous system. The half-life of the mutant protein in rats was slightly faster. The half-life of the mutant protein in humans will be determined in future studies.

“This finding is a necessary step in the development of antisense therapy,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association. “These data will be used to help decide when and how often we will need to measure remaining mutant SOD1, in order to judge the effectiveness of antisense treatment. In that light, this study represents true progress toward a trial.”

Read the press release.

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