Summary: A set of experiments at Standford reveals that suppressing a protein called Ataxin 2 dramatically extends survival and improves motor function in a mouse model of ALS.
ALS:
A study led by researchers at Standford University School of Medicine has discovered a new possible therapeutic approach for Amyotrophic lateral sclerosis- a progressive neurodegenerative disease. ALS is a disease in which the nerve cells in the brain and spinal cord degenerate, leading to wasting of the muscles. Patients gradually tend to lose their ability to move, speak, eat or breathe often resulting in paralysis and death within 2-5years.
ALS is inherited in an estimated 5-10 % of case. In rest of the cases, the cause is unknown. One of the indicator of ALS and other neurodegenerative diseases is the clumps of protein in the brain. These clumps are made up of protein called TDP-43. Removing TDP-43, and their aggregates might seem a good way to prevent or cure ALS. However, cells need TDP-43 to live, so suppressing this itself is not a good idea.
An Alternative approach to ALS:
A second protein Ataxin 2 helped cells survive when TDP-43 formed toxic clumps. Unlike TDP-43. Ataxin 2 is not necessary for cell survival, rendering it as a reasonable therapeutic target.
When tested with genetically engineered mice, by lowering the amounts of Ataxin 2 protein there was really an unprecedented survival, expanding their lifespan to hunderds of days.
Researchers attempted something that could have a more direct therapeutic impact: Treating mice with a type of DNA- like drug, designed to block the production of Ataxin 2. Called as “Antisense oligonucleotides” – they are called as strands of synthetic DNA that target a gene and block the expression of the protein that it encodes. Delivery of the Antisense oligonucleotides to the nervous system of some of the ALS affected mice enabled them to maintain their health much longer period than the ALS mice treated with a placebo.
A similar antisense oligonucleotide was approved recently for safety trials in pediatric patients with spinal muscular atrophy, and other antisense oligonucleotides have passed safety trials- a hope given by researchers for ALS.
The study exhibited that suppressing Ataxin 2 delayed the onset and progression of ALS-like disease in mice that were not yet showing symptoms. The question whether oligonucleotides could reverse symptoms of the disease is still unknown. The next set of experiments would focus on this question, says the researchers.