The hopes of many that ALS (commonly referred to as Lou Gehrig's disease) will one day be a disease of the past, studied in medical textbooks, conquered by the dedication of those who have worked tirelessly to eradicate it might be realized in our lifetime.
Sixty-plus years after Lou Gehrig, the New York Yankee's "Iron Horse," succumbed to ALS (amyotrophic lateral sclerosis), comes next-generation therapeutics with the potential to successfully treat ALS in this century.
CytRx Corporation, a Los Angeles-based biotechnology company, is working to tackle ALS with a double K-O punch. The company is researching potential therapies for the disease using both orally administered small molecules and RNA interference (RNAi), one of the most talked-about recent scientific breakthroughs.
ALS is a disorder affecting the function of nerves and muscles. Over 5,600 people in the U.S. are diagnosed with ALS each year (that's 15 new cases a day). It is estimated that as many as 30,000 Americans have the disease at any given time, with at least 120,000 people afflicted worldwide. The life expectancy of an ALS patient averages between two and five years from the time of diagnosis, and only half of all affected live more than three years after diagnosis.
CytRx is actively seeking to treat ALS through two approaches. The first approach is the potential use of orally administered small molecules to extend the life of ALS patients. To that end, the company recently acquired several promising small molecule drug candidates, including arimoclomol, for which the company plans to initiate a Phase II clinical trial for ALS in the second quarter of 2005.
Originally developed to treat diabetes, arimoclomol was recently discovered to significantly inhibit progression of ALS in a mouse model. Arimoclomol may provide cellular protection from abnormal proteins by activating molecular "chaperone" proteins that can repair or degrade the damaged proteins that are believed to cause many diseases, including ALS.
CytRx's second approach to treating ALS is through the use of RNAi technology (a form of gene silencing), with respect to which the company has an exclusive license from the University of Massachusetts Medical School (UMMS), one of the institutions at the forefront of RNAi technology.
In October 2003, CytRx initiated a research program headed by Robert Brown, Jr., M.D., Professor of Neurology at Harvard Medical School and founder of the Cecil B. Day Laboratory for Neuromuscular Research at Massachusetts General Hospital, to use RNAi technology to target the mutant SOD1 gene, which is responsible for many cases of the familial (or inherited) form of ALS. Ten years ago, Dr. Brown was among the scientists that discovered that a mutation in the SOD1 gene can be one of the causes the familial form of ALS.
ALS may have hindered the baseball prowess of the "Iron Horse," but it has fueled the passion of researchers such as Dr. Brown and those at CytRx to try to find a treatment and perhaps one day a cure.