Ask the Doc: Q & A with Edward Kasarskis, MD, PhD

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: What would you say are the biggest payoffs in ALS treatment? What are we reasonably able to expect might be the best and most likely outcome of continued research?

A: That’s a very interesting question. Most people simply ask, “When will we have a cure for ALS?” What people probably mean when they pose that question is “When will I be restored back to my previous level of health?” But many ALS patients tell me that they would be very pleased if their disease progression would be halted where it is.

At least in the near future, the "perfect" ALS drug would stop the ongoing degeneration and death of motor neurons in the spinal cord and brain, and therefore prevent any further progression of weakness.

Rilutek, of course, attempts to do that, but doesn’t go far enough. The gold medal for ALS drug development to borrow a term from the Olympics starting later this month in London would go to a drug that would stop degeneration in its tracks and prevent the disease from progressing any further. This would be a high value outcome, for sure.

To understand how this could come about, we need to dig a little deeper into the disease process. What’s interesting is that, early on, apparently healthy motor neurons try to fill in for the cells lost in the ALS process. We use this fact when trying to diagnose ALS in a patient. By this I mean that the neurologist doing the EMG test looks for larger "motor units" (sorry for the technical term but this refers to an individual spinal motor neuron and the number of muscle fibers that the single motor neuron connects to). This indicates that surviving, healthy motor neurons are essentially trying to “cover up” for the lost ones that are dead to ALS.

This is the process of "denervation" of muscle (loss of nerve connection to muscle) and "re-innervation" (the reconnection of muscle fibers to one of the remaining motor neurons). It’s a sign that all ALS motor neurons don't die off at once. This important fact offers hope that a drug could be developed to arrest the disease process in the spinal cord and halt progression of weakness. This also suggests that after such a drug stops the degeneration and death of motor neurons, it would also allow the reconnection of nerve to muscle and stabilization of muscle power.

The patient would recognize that the disease progression stopped. Imagine such a drug could be developed and available. The ALS patient would still have to live with some amount of permanent muscle weakness but the weakness would not progress further. Patients tell me that they would be able to handle this situation.

How could such an amazing drug be developed? The answer will probably involve finding a biomarker or biological signal that can identify the presence of ALS and measure its progression. Then you could take the drug and determine if the drug actually slows down, or stops the illness. Of course, the ultimate Holy Grail for ALS would be to be able to either restore/replace lost motor neurons using stem cells, or to prevent the disease altogether, perhaps through a vaccine. That accomplishment, at this point in time, is still quite far off into the future. The answer will only come with more research.

If you would like to submit questions for a future Q & A, please send your questions to theexchange@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.