By Jacob Ahlstrom | Posted - Oct 27th, 2020





A New Advancement in Gene Therapy for ALS Patients

In a press release this week Ionis Pharmaceuticals, a leader in gene therapy treatments, announced its first gene therapy medication designed to treat sporadic ALS. Gene therapy is one of today’s biggest advancements in treating neurological diseases such as ALS. Gene therapy can reduce the effects of a mutated gene without having to repair the gene itself.  

Up until now, biotech teams have only developed drugs that specifically treat the known mutations in genetic ALS cases called familial ALS (fALS). These fALS cases only make up about 10-15% of all ALS patients leaving 9 out of 10 patients without gene therapy as a potential option before now.  

Last week Ionis Pharmaceuticals announced that the first ALS patients were dosed with ION541, a potential therapy that will hopefully treat most forms of ALS, marking the beginning of the clinical trial phase 1/2. This therapy is different than its predecessors in that it will impact a broader spectrum of ALS patients if successful.  

From the outside, ALS looks fairly similar across the board. Aside from differences in location of disease onset, most ALS cases look the same. Without more information, familial and sporadic ALS are impossible to tell apart before DNA testing. Although they appear similar the molecular differences between fALS and sALS are noticeably clear making it difficult to find a treatment for both types of ALS. After further investigation, researchers at Ionis have found a protein malfunction that is consistent in almost all ALS cases.  

The protein under investigation is called TDP-43 and it is known to build up in motor neurons, becoming toxic to the cell and causing cell death. The protein TDP-43 plays a key role in cell function so it cannot be targeted directly but preclinical data suggest that these clumps can be reduced by eliminating another protein in the cell. The drug ION541 targets this second protein called ataxin-2 in order to reduce the toxic TDP-43 protein concentrations.  

So, what does the clinical trial phase 1/2 look like? In all clinical trials, there are multiple phases of testing. Phase I aims to find the best dose for a new drug. Phase II further evaluates drug safety and function. The drug ION541 is being tested for safety as the primary focus of testing. Investigating how the drug behaves in the patient’s body is a key secondary objective.  

Patients will be given increasing doses of treatment injected into the spine every two days. The estimated trial completion date is February 2023 according to  

Ionis has already developed 2 other ALS therapies similar to this one but the difference is that they target familial ALS, leaving out 90% of ALS patients.  

Frank Bennett, Ph.D., and chief scientific officer at Ionis told the press, "As our third medicine designed to treat different forms of ALS to enter clinical trials, ION541 represents yet another example of the power of Ionis' [gene therapy] technology to potentially target root causes of devastating neurodegenerative diseases," 


Although there is too much time between now and when this drug could potentially be approved, Ionis has made other advancements that may be just around the corner. Their drug called Tofersen is currently in Phase 3. It is designed to reduce the production of the SOD1 (superoxide dismutase 1) gene (a common gene mutation in familial ALS cases) and is showing promising results. We can expect to see the Toferson clinical trial results in 2021. Ionis is also working on a drug to reduce the mutant C90RF72 gene which is the most common genetic ALS mutation. This is the first drug of its kind to enter clinical development and it received Fast Track designation from the FDA (Food and Drug Administration) this year.  


Jacob Ahlstrom
About the Author

Jacob Ahlstrom - Jacob is a Neuroscience undergraduate at Brigham Young University. Jacob's interest in researching and writing about ALS is fueled by his hope to make the process easier for everyone else. Over the last year he has worked alongside Seth Christensen to find ways to educate and connect ALS patients.