Pinpointing the Protein Problem in Lou Gehrig’s Disease
Colón is Awarded $1 Million From the NIH to Study
the Cause of the Disease
Troy, N.Y. — 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
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
The Rensselaer biochemist’s vital research has recently earned
a $1 million, four-year grant from the National Institutes of
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
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
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
“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
According to the National Institutes of Health (NIH), 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.
Contact: Megan Galbraith
Phone: (518) 276-6531