Copyright 2004 PR Newswire Association, Inc.  
PR Newswire
April 27, 2004, Tuesday 2:23 PM Eastern Time
SECTION: FINANCIAL NEWS
DISTRIBUTION: TO BUSINESS, MEDICAL AND HEALTH EDITORS
LENGTH: 1137 words
DATELINE: SAN DIEGO, April 27

In preclinical studies, an antisense drug suppressed the production of the mutant protein Cu/Zn superoxide dismutase (SOD1), a molecule associated with an aggressive form of amyotrophic lateral sclerosis (ALS).  Researchers believe that decreasing the amount of mutant SOD1 in the brain of patients with this condition could potentially modify or halt the progression of the disease.  Previous attempts to specifically inhibit SOD1 expression using traditional inhibition technology have proven unsuccessful.  Leading neurodegenerative investigators Richard A. Smith, M.D., Center for Neurologic Study, and Don Cleveland, Ph.D., UCSD Ludwig Institute for Cancer Research, San Diego, conducted this study with funding from The ALS Association.  Dr. Smith presented the findings today at the 56th Annual Meeting of the American Academy of Neurology. 

In the study, Drs. Smith and Cleveland administered the antisense inhibitor intraperitoneally (directly into the abdomen) and intraventricularly (directly into the brain) to rodents expressing SOD1 over a period of weeks. Rodents receiving the antisense inhibitor intraperitoneally showed a 90% reduction in SOD1 messenger RNA (mRNA) expression in the liver, an organ in which antisense drugs readily accumulate.  Animals receiving the inhibitor intraventricularly showed a 50% reduction in SOD1 mRNA levels in brain and spinal cord tissues, accompanied by a significant reduction in SOD1 protein levels.  Based on these findings, researchers concluded antisense drugs targeting SOD1 could potentially benefit people with ALS.  Drs. Smith and Cleveland collaborated with Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) to develop the proprietary antisense inhibitor. 

"If these drugs work as well in humans as they do in the laboratory, there is a good chance we can come up with a molecular therapy for familial ALS as well as for other neurodegenerative disorders," said Dr. Smith.  "Although a relatively small group of patients have this much more aggressive form of ALS, they typically have shorter survival rates than the majority of ALS patients. It is our hope that we could slow or arrest disease progression using an antisense therapeutic in this subgroup of patients." 

"This study is an excellent example of the versatility of antisense to target disease-associated proteins that cannot be approached with other technologies due to lack of specificity," said Frank Bennett, Ph.D., Vice President of Antisense Research for Isis.  "Drs. Smith and Cleveland's findings are encouraging and we hope to move these compounds forward in order to better understand their potential for treating this form of ALS and to broaden the application of antisense into numerous neurodegenerative disorders."

About the Investigators 

Dr. Don Cleveland is in the Ludwig Institute for Cancer Research and Professor of Medicine, Neurosciences and Cellular and Molecular Medicine at the University of California, San Diego.  Dr. Richard Smith is Director of the Center for Neurologic Study in San Diego and a Skaggs Clinical Scholar at Scripps Research Institute.  Both are members of the Laboratory for ALS Research in San Diego. (http://ludwig.ucsd.edu/ClevelandLabCMM/ALSgroup.html).