ALS Trial: Novel Therapy is Safe

04/25/2013
Photo: Protein

A mutated protein that causes an inherited form of Lou Gehrig’s disease leads to clumps in the human cells in the bottom image. A therapy that blocks production of this protein has passed phase 1 safety trials;
© WUSTL

An investigational treatment for an inherited form of Lou Gehrig’s disease has passed an early phase clinical trial for safety, researchers at Washington University School of Medicine in St. Louis and Massachusetts General Hospital report.

The researchers have shown that the therapy produced no serious side effects in patients with the disease, also known as amyotrophic lateral sclerosis (ALS). The phase 1 trial’s results also demonstrate that the drug was successfully introduced into the central nervous system.

The treatment uses a technique that shuts off the mutated gene that causes the disease. This approach had never been tested against a condition that damages nerve cells in the brain and spinal cord.

“These results let us move forward in the development of this treatment and also suggest that it’s time to think about applying this same approach to other mutated genes that cause central nervous system disorders,” says lead author Doctor Timothy Miller. “These could include some forms of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and other conditions.”

ALS destroys nerves that control muscles, gradually leading to paralysis and death. For treatment of the disease, the sole FDA-approved medication, Riluzole, has only a marginal effect. Most cases of ALS are sporadic, but about 10 percent are linked to inherited mutations. Scientists have identified changes in 10 genes that can cause ALS and are still looking for others.

The study focused on a form of ALS caused by mutations in a gene called SOD1, which account for 2 percent of all ALS cases. Researchers have found more than 100 mutations in the SOD1 gene that cause ALS.

“At the molecular level, these mutations affect the properties of the SOD1 protein in a variety of ways, but they all lead to ALS,” says Miller. Rather than try to understand how each mutation causes ALS, Miller and his colleagues focused on blocking production of the SOD1 protein using a technique called antisense therapy.

To make a protein, cells have to copy the protein-building instructions from the gene. Antisense therapy blocks the cell from using these copies, allowing researchers to selectively silence individual genes.

“Antisense therapy has been considered and tested for a variety of disorders over the past several decades,” Miller says. “For example, the FDA recently approved an antisense therapy called Kynamro for familial hypercholesterolemia, an inherited condition that increases cholesterol levels in the blood.”

MEDICA.de; Source: Washington University School of Medicine in St. Louis