Tiny fish could be key to ALS breakthrough

Gary Armstrong uses an aquarium in his new drug-screening program

Gary Armstrong has high praise for zebrafish, a species of fish that he is using to look for new ways to treat amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease that has defied a cure and effective treatments.

“It’s a tiny fish that’s been used in research for a long time because researchers can manipulate their genome in precise ways,” says Armstrong, who joined The Neuro in 2017 as an assistant professor in McGill University’s Department of Neurology and Neurosurgery. “As a genetic model for testing drugs, they’re fantastic. I can make the same genetic mutations in these fish that cause ALS. Moreover, with the new equipment that I have, I can test drugs on hundreds of fish at a time, which creates a wonderful drug-screening platform.”

Armstrong’s activity falls into the category of translational biomedical research, which aims to refine laboratory discoveries in a short time period and at low cost before the discoveries undergo lengthy, costly clinical trials. A key advantage of zebrafish is their small size. Adult zebrafish can be bred by the dozens each week and experiments can be performed on the thousands of juvenile fish at little expense. Test drug compounds are simply added to the water in which the fish are living.

Purchased with money from a generous private donor, the zebrafish motion tracker system called DanioVision developed by Noldus is small enough to fit on a desk. It is capable of monitoring the movement of huge numbers of fish so that a researcher can spot signs of ALS. Drug compounds can be tested on these fish to see whether the symptoms can be stopped. Rather than having the researcher test drugs by hand one chemical at a time, the motion tracker can screen thousands of potential chemicals rapidly and in an unbiased way.

“I have different ALS models because we know at this point of about 35 different genes that are involved in ALS, causing different defects at the cellular level. Although ALS manifests symptoms similarly among patients, the cellular defects can be very different from one patient to the next. So in our models, our test drugs target different things.”

“ALS remains a relentlessly progressive and devastating disease. But considerable advances have been made and these discoveries have opened the door to innovative approaches to the study of cellular defects that arise in ALS. This gives us hope.”

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