The ALS Association, a national nonprofit organization based in Wash. D.C., has awarded $326,662 in research funds to expand ongoing natural history studies in order to further understand the most common genetic cause of ALS, in preparation for clinical trials in those whose disease is affected by this gene.
ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig's Disease, is a progressive neurodegenerative disease that affects neurons (nerve cells) in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. There is no cure and no life-prolonging treatments for the disease.
Mutations in the C9orf72 gene cause approximately 40% of all familial cases of ALS and up to 6% to 8% of sporadic cases. In the mutant gene, a small portion of the gene carrying a repeated string of DNA letters is greatly expanded to hundreds or thousands of repeat units. Researchers believe that antisense oligonucleotide therapy is a promising approach to reducing the harmful effects of this gene, based on extensive preclinical work and the demonstration that antisense therapy in people with ALS is feasible and safe.
"In order to prepare for such a clinical trial, it is crucial that we learn much more about the normal clinical course of ALS due to the C9orf72 gene," said Lucie Bruijn, Ph.D., M.B.A., chief scientist for the association, "as well as how the length of the repeated section correlates with clinical features, such as onset, progression and duration of the disease. In addition, C9-related biomarkers in blood or cerebrospinal fluid are needed to be able to quickly assess disease progression."
Those studies, already funded by Biogen Idec, are ongoing at Washington University in Saint Louis, Massachusetts General Hospital in Boston and the University of Massachusetts Medical Center in Worcester, Mass. The new award will fund expansion of these studies to Johns Hopkins University in Baltimore, the University of California at San Diego, Cedars-Sinai Medical Center in Los Angeles and University Medical Center Utrecht, the Netherlands.
"We are enthusiastic about expanding these studies, which will establish the clinical data and biomarkers needed to successfully plan a clinical trial for C9orf72 ALS patients," said Timothy M. Miller, M.D., Ph.D., associate professor of neurology at Washington University in Saint Louis.