Results of the proof-of-concept study could lead to treatments for multiple neurodegenerative disease, say researchers
![professor of neurology Robert H. Brown Jr., MD, DPhil: “This intervention targets not only the mutant allele but the miscreant transcripts and DPRs [dipeptide repeats] generated by that allele..." UMass Chan Medical School](https://precision-medicine-institute.com/wp-content/uploads/Robert-Brown-DPhil-MD-UMass-sm.jpeg)
Researchers at UMass Chan Medical School have successfully developed a treatment to suppress mutant forms of a gene that causes amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. The successful therapeutic, according to a UMass news release, could “catalyze research into treatments for ALS, formal thought disorder (FTD), and other neurodegenerative diseases.”
ALS is a neurological disease that slowly destroys any ability to move muscles throughout the body. It causes degeneration of the motor function of the neurological system but leaves the ability to feel and think completely intact.
ALS is always fatal, and despite aggressive research in this area, until now there have been no effective treatments to slow or stop the progression of the disease.
However, the UMass research team, led by Robert H. Brown Jr., MD, DPhil, and Jonathan Watts, PhD, recently performed a single-patient pilot study of a new treatment for ALS that may soon be available to hospitals and neurologists.
The UMass scientists published their findings in the journal Nature Medicine, titled, “Suppression of Mutant C9ORF72 Expression by a Potent Mixed Backbone Antisense Oligonucleotide.”
First Time ASO Used to Treat ALS
The therapeutic, called antisense oligonucleotide (ASO) therapy, blocks the expression of specific genes. ASOs are strands of molecules that attach to specific strands of messenger RNA (mRNA), the genetic material that cells use to copy DNA into proteins. By creating specific strands of ASO, the researchers were able to specifically target the mutant C9ORF72 gene and inhibit its expression.
“ASOs are essentially anti-messenger RNA agents. Using the genetic sequence you want to target, you can design an antisense oligonucleotide sequence that binds to that mRNA so the mutant protein never gets made,” said Watts, an associate professor with the RNA Therapeutics Institute at UMass Medical School, in the news release. “Once you’ve established how to deliver an ASO to a certain type of cell, theoretically it should be possible to repeat for other neurodegenerative diseases. All you’d have to change is the nucleotide sequence.”
The UMass team is the first to use ASOs to treat a patient with ALS. “While other teams have documented that this gene can be suppressed in cells in culture, this is the first time this type of antisense oligonucleotide treatment for C9ORF72 ALS has been demonstrated in a person with ALS,” said Brown, the Leo P. and Theresa M. LaChance Chair in Medical Research and professor of neurology at UMass Chan Medical School.
Bringing Precision Medicine to ALS Patients
The single-patient pilot study results are promising. During the 13-month proof-of-concept study, the scores used to measure the progression of ALS in the patient were unchanged or slightly improved. This may indicate the progression of the disease was essentially stopped. The patient also did not experience any adverse effects from the treatment.
While ALS is a very rare disease, it is considered to cause more suffering than most terminal diseases. ALS currently has a 100% fatality rate with almost no treatment options. The ability to leverage the benefits of precision medicine to stop the progression of ALS would be a tremendous breakthrough, potentially providing hope for thousands of patients.
“The results are very encouraging,” Brown said. “It means this is a viable approach to suppressing the mutant C9ORF72 protein that causes most cases of familial ALS.” The next step is to launch a multi-person clinical trial to see if this treatment can slow progression of the disease.”
Hospitals and neurology leaders should be aware of this promising treatment for ALS. It may be available for patients in the near future. Hospitals could even seek to participate in future multi-person clinical trials and offer their neurology patients the opportunity to participate in this innovative precision medicine research.
—Caleb Williams
Related Information:
Suppression of Mutant C9ORF72 Expression by a Potent Mixed Backbone Antisense Oligonucleotide