Scientists use DNA to slow ALS in rats
August 4 2006 | ALS Research
By Bruce Lieberman
UNION-TRIBUNE STAFF WRITER
August 3, 2006
San Diego researchers have demonstrated in animals a new approach toward treating amyotrophic lateral sclerosis, suggesting that the deadly nervous system disease may someday be treated as a chronic but manageable illness.
Their method slowed the progression of the disease, also known as ALS or Lou Gehrig's disease, in rats. The findings are described in the August issue of the Journal of Clinical Investigation.
The scientists hope to begin clinical trials with humans next year.
“This is a very hopeful development, and . . . a lot of people who have thought about it think it will work,” said Dr. Richard A. Smith, who co-authored the study and treats ALS patients at the Center for Neurologic Study in La Jolla.
Using synthetic fragments of DNA called antisense oligonucleotides, Smith and his colleagues suppressed a defective gene in the rats called SOD1 that causes ALS.
The gene is implicated in only about 2 percent of all ALS cases. But scientists said they were particularly excited by how the synthetic DNA successfully spread throughout the rats' nervous system to several brain regions affected by other diseases.
The key was to inject the synthetic DNA directly into the brain or administer it with a pump into the spinal column, where it was circulated by a fluid that bathes both.
As a result, the DNA fragments reached parts of the brain damaged by ALS as well as Alzheimer's, Parkinson's and Huntington's diseases.
“We didn't know that before – that we could deliver effective doses to all the major brain regions,” said Don Cleveland, whose lab at the University of California San Diego conducted the study. He worked with Smith and fellow UCSD researcher Timothy Miller.
The synthetic DNA inhibited both the healthy and defective forms of SOD1, but the scientists did not detect any adverse reaction in the rodents they tested, Cleveland said.
Whether the treatment will work in humans is another matter.
“Will administration of this class of compounds into humans really be safe?” Cleveland asked. “You never know that without an initial clinical trial.”
Isis Pharmaceuticals Inc. in Carlsbad provided the synthetic DNA for the study, and the firm is expected to manufacture it for clinical trials. Cleveland and Smith, who also is a researcher at The Scripps Research Institute in La Jolla, are consultants for the company.
The ALS Association, based in Calabasas Hills, paid for the study.
Amyotrophic lateral sclerosis afflicts about 20,000 Americans, and about 5,000 more are diagnosed annually, according to the National Institute of Neurological Disorders and Stroke.
The disease typically strikes people 40 to 60 years old, killing nerve cells called motor neurons, which control voluntary muscles. It progresses rapidly, robbing patients of their ability to move their arms, legs and other parts of the body.
Eventually, it causes the patient to stop breathing. Most ALS patients die within five years after onset of the disease.
