Potential New Treatment for Patients with Lou Gehrig's Disease

California-based Isis Pharmaceuticals may have discovered an effective treatment for Amytrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease -- a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord.

The treatment, ISIS-SOD1RX, is designed to shut down the RNA that enables the production of disease-causing proteins and targets superoxide dismutase, or SOD1, a molecule associated with an inherited, aggressive form of ALS. This new approach to inhibit the production of these types of proteins was developed by Isis as part of its "Antisense" drug platform that could potentially be used to treat a variety of neurological disorders, including Parkinson's and Huntington's disease.

Isis has targeted RNA molecules because they affect the expression of all genes. RNA is also a simpler molecule than proteins in that it is composed of four fundamental building blocks called nucleotides (A,C,U,G). Proteins are made from 20 different building blocks called amino acids.

Researchers have reported in the Journal of Clinical Investigation that ISIS-SOD1Rx prolonged life in rats showing many symptoms of ALS. They also stated that by delivering the drug directly to the fluid that circulates within the central nervous system, they were able to lower production of the mutant protein in neurons and surrounding cells.

Initially, Isis encountered problems testing its antisense treatment methods due to the molecules being too big to pass through the blood-brain barrier when they are delivered by conventional injection under the skin. The blood-brain barrier is a physiological mechanism that alters the permeability of brain capillaries, so that some substances such as certain drugs, are prevented from entering brain tissue, while other substances are allowed to enter freely.

Isis developed a reformulated version that could be delivered through infusion with a spinal tap device. This novel treatment, which Massachusetts-based Genzyme has an option to co-develop, is being prepared for an upcoming clinical trial later this year.

ALS affects 5,600 new patients annually in the U.S. Currently there is no cure for the disease.