The researchers, led by teams from The Research Institute at Nationwide Children's Hospital and the Ludwig Institute at the University of California, San Diego, found a survival increase of up to 39 percent in animal models with a one-time treatment, a crucial step toward moving the therapy into human clinical trials.
The therapy reduces expression of a gene called SOD1, which in some cases of familial amyotrophic lateral sclerosis (ALS) has a mutation that weakens and kills nerve cells called motor neurons that control muscle movement.
While many drug studies involve only one type of animal model, this effort included analysis in two different models treated before and after disease onset.
Brian Kaspar, PhD, a principal investigator in the Center for Gene Therapy at Nationwide Children's and a senior author on the research, said that they designed these rigorous studies using two different models of the disease with the experimenters blinded to the treatment and in two separate laboratories.
Ideally, a therapy would hit motor neurons and astrocytes equally hard. The best way to do that is to deliver the drug directly into the cerebrospinal fluid (CSF), which would reduce the amount of SOD1 suppression in cells outside the brain and reduce immune system exposure to AAV9-elements that would add weight to an argument for studying the drug in humans.
Injections directly into CSF cannot be done easily in mice, so the team took the study a crucial step further by injecting AAV9-SOD1-shRNA into the CSF of healthy nonhuman primates.
The results were just as the team hoped-the amount of gene expression dropped by as much as 90 percent in motor neurons and nearly 70 percent in astrocytes and no side effects were reported, laying the groundwork towards moving to human clinical trials.
The study has been published online in Molecular Therapy.
--ANI (Posted on 10-09-2013)