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Mayo Clinic study unveils unprecedented method to predict ALS, Parkinson's 
disease
ROCHESTER, Minn. -- A new Mayo Clinic study details an unprecedented method to 
predict brain aging disorders such as amyotrophic lateral sclerosis (ALS, or 
Lou Gehrig’s disease) and Parkinson’s disease. Investigators studied common 
variations within axon guidance pathway genes and identified several gene 
variations (DNA fingerprints) that collectively predicted people who are at a 
high risk for ALS (2,000 times greater than the average risk). They also 
identified several gene variations that collectively predicted people at a 
high risk for Parkinson’s disease (nearly 400 times greater than the average 
risk).
The probability that the findings were by chance was extremely small (less 
than one in a trillion). The axon guidance pathway consists of a complex 
array of chemical signals that wires the brain during fetal development and 
maintains and repairs brain wiring throughout life. The study is published 
online in the public access journal PLoS ONE. (www.plosone.org/home.action)
“The mission of our research is to predict, prevent and halt brain aging 
disorders,” explains Demetrius Maraganore, M.D., Mayo Clinic neurologist and 
principal investigator. “I envision a day when we will be able to do a simple 
blood test and predict whether a person is at high risk to develop brain 
aging disorders such as ALS, Parkinson’s disease and even Alzheimer’s disease 
by studying common gene variations in disease pathways. In persons at high 
risk, we may be able to prevent the diseases or slow or halt their 
progression by developing drugs that target the same disease pathways. For 
ALS and Parkinson’s disease, our study is a major step in these directions.”
About the Study
 
In June 2007, the investigators reported similar findings for Parkinson’s 
disease. However, with this new study they extended their findings to ALS, 
where they observed greater effects. The investigators noted that while up to 
50 percent of the axon guidance pathway genes that predict ALS or Parkinson’s 
disease are in common, there also are gene variations that are specific to 
either disease. This may help explain the similarities and differences that 
are seen in persons with these diseases, or the clustering of such diseases 
that sometimes occur within isolated populations or families.
The investigators obtained these results by analyzing publicly available 
datasets of whole-genome variations in people with ALS, Parkinson’s disease 
and those who did not have neurological disorders. The datasets were released 
recently by the Coriell Institute and the National Institutes of Health. The 
investigators developed and applied to the data a genomic pathways approach.
“The size of the effects that were observed and their statistical significance 
are unprecedented in the study of brain aging disorders. I attribute our 
success to the genomic pathways approach we developed,” adds Timothy Lesnick, 
Mayo Clinic biostatistician. “Now we need to develop a better map of the gene 
variations within the axon guidance pathway and make comparisons across 
multiple brain aging diseases and populations.”
ALS causes degeneration of the nerve cells in certain regions of the brain and 
spinal cord that control a person’s voluntary muscles. Eric Sorenson, M.D., 
and Eric Ahlskog, M.D., Ph.D., Mayo Clinic neurologists specializing in ALS 
and movement disorders, agree that impairments in brain wiring and repair are 
plausible causes of ALS and Parkinson’s disease. Investigators agree that 
additional research is needed to continue the success obtained in this study.
“I envision experiments in cultured cells and animal models to define the most 
important treatment targets within the axon guidance pathway,” says John 
Henley, Ph.D., Mayo Clinic neuroscientist and expert on brain wiring and 
repair processes. 
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