TROY, NY – The cause of Lou Gehrig’s Disease (ALS or amyotrophic lateral sclerosis) has remained elusive since it brought down one of baseball’s greatest players 60 years ago.
According to Wilfredo “Freddie” Colón, ALS starts “when good proteins go bad.” Understanding just why they go bad is a necessary first step toward developing medicines that will help ALS patients live with a manageable disease instead of a death sentence.
The Rensselaer biochemist’s vital research has recently earned a $1 million, four-year grant from the National Institutes of Health.
The NIH grant will support Colon’s study of the hereditary version of the disease, called familial ALS or FALS. He is attempting to understand why mutants of the enzyme superoxide dismutase (SOD1) fail and misfunction in FALS.
On average, FALS strikes people who are around 47 years of age, says Colon. Most patients die within two to five years. But some patients, whose proteins exhibit a different kind of mutation, experience a very slow progression and can survive for as long as 18 years, says Colón.
The existence of SOD1 mutants associated with this “milder” form of FALS makes it an intriguing biophysical and biochemical marker. Unlocking the mystery of the pathogenic causes for FALS could also play an important role for better understanding other neurogenerative disorders, such as Parkinson’s and Alzheimers.
SOD1 is an enzyme that normally breaks down free radicals, highly reactive molecules that quickly damage DNA and proteins, thereby, endangering cells. However, the genetic defect that results in SOD1 mutations does not cause FALS because the normal function has been affected. Instead, a new mysterious toxic function of SOD1 leads to the death of motor neurons.
Faulty SOD1 behavior, caused by a number of different genetic mutations, is at the root of roughly one-fifth of inherited or familial ALS (FALS) cases. Around 10 percent of ALS cases are familial (FALS) and of those, 20 percent involve a mutation of the SOD1 gene, says Colón.
“What is it that these mutations do to the protein to make it pathogenic?” Colón says. “That is what we are looking at here. We finally have a molecular target to aim at, which may provide us some understanding of the pathological mechanisms of FALS.
“If we know what the pathological mechanism is, we could devise drugs to block it,” Colón continues. “Just knowing which protein is different is not enough. We need to do the biochemistry at the molecular level to understand what these mutations are doing to the protein. If we’re successful, it could provide a target for drug development and therapy. All this, however, is hard to do until you know what’s wrong with the protein.”
According to the National Institutes of Health (NIH) (http://www.ninds.nih.gov/health_and_medical/pubs/als.htm), ALS is the most common neuromuscular disease worldwide. In the U.S. there are 20,000 people with the disease and 5,000 people are diagnosed each year.
About Rensselaer
Rensselaer Polytechnic Institute, founded in 1824, is the nation’s oldest technological university. The school offers degrees in engineering, the sciences, information technology, architecture, management, and the humanities and social sciences. Institute programs serve undergraduates, graduate students, and working professionals around the world. Rensselaer faculty are known for pre-eminence in research and teaching. The Institute is especially well known for its success in the transfer of technology from the laboratory to the marketplace so that new discoveries and inventions benefit human life, protect the environment, and strengthen economic development.
For a print-quality, four-color version of the protein, go to: http://www.rpi.edu/dept/NewsComm/sub/newsimages/protein.jpg
