New Genetic Risk Factor for ALS

Amyotophic lateral sclerosis, also referred to as Lou Gehrig's diseasde is a disease in which there is progressive degeneration of the motor cells in the spinal cord and brain.  The degeneration inhibits nerve impulses from reaching muscles and the person will soon experience muscle weakness and eventually deterioration.  There is no known cure for ALS.  In recent studies biologists and neuroscientists have been ablidene to locate and identify a  new genetic risk factor.  They found evidence that mutations in the ataxin 2 gene were a genetic contributor to the disease.  The study showed that expansions of a run of the amino acid, glutamine, in ataxin 2 were associated with an increase risk for ALS, a frequency of 4.6% for all ALS cases studied.  Since there is no cure, only treatments that slow progression this new information combined with known information about the relationship of TDP-43 to ALS may be able to offer new types of therapy to slow the disease even further.
The experiment was first carried out on yeast genes and studying TDP-43.  They then began studying on fruit flies, confirming the results they had with yeast and showing that ataxin 2 was a potent modifier of TDP-43.  The higher the levels of ataxin 2, the higher the level of toxicity was in the fruit fly.  Ataxin 2 has been related to other spinal cord diseases and it is now apparent that the more ataxin 2 glutamine repeated stretches a person has, the greater their risk for ALS.


A role for the polyQ protein ataxin 2 in ALS was identified using yeast (top left), fruit fly models (top middle), human ALS motor neurons (top right) and genetic analysis in ALS patients (above). (Credit: University of Pennsylvania)