A treatment targeting the gene ataxin-2 has reduced symptoms in mice of two neurodegenerative diseases for which there are currently no treatments.
In mice with a type of ataxia called spinocerebellar ataxia type 2, targeting this gene led to improved coordination and balance in mice two months later, scientists report in a paper on the treatment of ataxia in Nature.
Patients with this type of ataxia often present with symptoms including slurred speech and difficulty balancing and walking, which can resemble drunkenness. This is caused by the death of brain cells and decreased activity in the cerebellum, a region of the brain involved in movement and coordination. In advanced stages, this type of ataxia can appear much like advanced ALS, with difficulty moving, swallowing and breathing.
The treatment targeted the gene by using 'antisense oligonucleotides' tailored to the product of the ataxin-2 gene, a strand of mRNA. The antisense oligonucleotide binds to the ataxin-2 mRNA before it can be used to make a harmful protein. Once bound to it, an enzyme in the cell called RNAse-H breaks down the mRNA-antisense oligonucleotide hybrid.
In mice with a condition mimicking ALS, a very similar treatment targeting the same gene led to reduced symptoms and extended life expectancy. The results are also published in the journal Nature on a paper on ALS.
The gene ataxin-2 isn't directly implicated in ALS, but variations of the gene have been identified as a risk factor for the disease. It's thought that the protein of the ataxin-2 gene causes a protein called TDP-43, which causes the symptoms of ALS. In mice with the ALS-like condition, their lifespan was increased by about a third after treatment with the antisense DNA.
The findings are proof-of-concept for antisense oligonucleotide therapies for these neurodegenerative diseases, and potentially other related diseases in humans. A similar type of treatment based on antisense oligonucleotides was recently approved by the US's Food and Drug Administration in December for a disease called spinal muscular atrophy. This method of treatment is also being used in a clinical trial for Huntingdon's disease.
"It is encouraging that these other trials using antisense oligonucleotides shows that it's safe and can be effective for other neurodegenerative diseases," Aaron Gitler of Stanford University School of Medicine and author of the ALS study told IBTimes UK. "It makes the path clearer for ataxin-2."
The next steps towards the treatments are further tests in different animals, and testing how effective the treatments are in human cells in a dish. If these prove to be safe and promising, human trials will be further down the line.
"Our combined work is an example of how understanding a rare disease can impact more than the small number of people affected by it," said Stefan Pulst of the University of Utah and an author of both studies. "It is leading to insights into treatments for more common diseases."