Edward Kasarskis, M.D., Ph.D. is Director of the multidisciplinary ALS Center at the University of Kentucky Neuroscience Center in Lexington, Kentucky, professor in the Department of Neurology at the University of Kentucky, and Chief of Neurology at the VA Medical Center in Lexington KY. 

Dr. Kasarskis

Q: I just heard about a new gene discovery associated with ALS. Is this really a big breakthrough, or just hype?

A: Actually, we’ve had two big discoveries in the last two months. First, research published in the journal Nature in August by scientists at Northwestern University Feinberg School of Medicine found a new gene linked to familial ALS, a gene involved in how cells process accumulated proteins. This work builds on the concept of abnormal protein handling as a cause of ALS.

Then, in late September, two studies published in the journal Neuron (both funded by The ALS Association) found a genetic abnormality on chromosome #9 that they think is the most common cause of ALS and frontotemporal dementia (FTD). Using advanced gene sequencing techniques, two independent teams of researchers found the same defective gene. They think that when that gene is transcribed into a messenger RNA molecule, it causes RNA to bind tightly with some proteins, forming clumps that somehow serve to derail normal functions in the cell. The abnormality, the researchers say, accounts for about 50% of familial ALS cases in Finland and more than a third of familial cases in other European populations. The gene defect is also the most significant genetic risk factor yet found for sporadic ALS; it was found in 3% of sporadic FTD and 4% of sporadic ALS samples in another study.

Much of this success is thanks to the many patients and families who have been willing to donate blood samples for gene discovery. Their participation and involvement in this work is a significant and notable gift toward ALS research.

At this point we do not know the percentage of familial and sporadic ALS cases associated with these genes. We also don’t know how prevalent the gene will be in Americans or people of non-European descent. We need to expand this work to include a broader range of population groups.

However, the research is indeed significant because it fits with the current thinking about causes of ALS and builds on previous discoveries, especially the important work done over the last several years to better understand the role of the SOD-1 gene. The research will help direct further investigation of the individual genes and their protein products. When we look -- at autopsy -- at spinal cords of people who had ALS, we see abnormal aggregations in the nerve cells. We will soon come to understand how the normal cell eliminates worn-out proteins, and from that research we hope to learn how to turn on or off key genes, or the proteins themselves, to augment normal function. That’s when therapeutic solutions will be designed and tested.

So, to answer your question more directly: it isn’t hype. We’re chipping away at the mystery of unknown genes, and the percentage of what we know is starting to grow by leaps and bounds.

If you would like to submit questions for a future Q & A, please send your questions to Amber Walters at awalters@alsa-national.org. Please understand that we won't be able to address all questions and we won’t be able to respond to individuals personally.