A research team from Quebec has identified a mechanism that may be able to halt the paralysis caused by amyotrophic lateral sclerosis, or ALS.
ALS is neurodegenerative disease sometimes known as Lou Gehrig’s disease. It attacks the neurons which control movement, leading to rapid paralysis.
The disease is incurable with a life expectance of two to five years after diagnosis.
Professor Kessen Patten of the Institut national de la recherche scientifique, who led the new study, says most other research has centred on the motor regions of the brain.
The Montreal team chose to focus instead on the cerebellum, which is a brain region associated with balance and coordination.
Patten says research conducted on zebrafish found the disease may begin outside the motor regions of the brain before the first visible symptoms appear — which could eventually lead to earlier diagnosis and better treatment.
“It is known in ALS that there’s DNA damage and problems with DNA repair,” Patten said. “And we have identified the enzyme responsible for this defect.”
The experiments on zebrafish — which share many genetic and cellular mechanisms with humans — revealed to scientists early cerebellar atrophy, characterized by the loss of two essential types of neurons.
The research suggests that ALS, like other neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and multiple sclerosis, begins to develop gradually, several years before manifesting openly.
The team detected a decrease in the activity of a gene that produces an enzyme essential for the synthesis of purines, which are molecules used in the construction and repair of DNA.
This decrease in activity means DNA damage can accumulate and cellular repair systems fail, leading to cell degeneration.
Patten said identifying this mechanism could lead to better patient screening. “If there are ALS carriers in the family, we believe that imaging of the cerebellum could be performed early on, before the onset of motor symptoms,” he said.
Best of all, the researchers found the mechanism they discovered might be reversible. In an experimental model, researchers succeeded in restoring the activity of the gene, which led to reduced damage, better neuron survival, and a halt in disease progression at the cellular level.
While scientists are far from curing ALS, Patten says the discovery could lead to better therapies or even useful supplements. “I’d like to know if there’s something we can start doing earlier, for example in familial cases where we know there’s a genetic component, but symptoms haven’t appeared yet,” Patten said.
Between 3,000 and 4,000 people live with ALS in Canada.
The findings of the study were published in the medical journal Brain.
