10 Questions and Answers from ALS Unfiltered: May 2019

On May 14, 2019, the ALS Therapy Development Institute (ALS TDI) hosted an ALS Unfiltered webinar session as part of ALS Awareness Month. Over 200 people from around the world attended the hour-long webinar, led by Gabby Bellitti and CEO Dr. Steven Perrin, to learn more about current ALS drug research and resources. In line with ALS Awareness Month’s #AskMeAboutALS theme, we asked listeners for their questions about the disease, drug development research, and clinical trial progress. Here are answers to 10 of the most pressing questions we received, edited for clarity.

• What advantage does Edaravone (also known as Radicava or MCI-186) have over readily available anti-oxidant products (Curcumin, CoQ10, Isoquercetin, VitC, etc.)?
  • Edaravone, also known as Radicava or MCI-186, was approved by the FDA in 2017 and has been shown to have some therapeutic benefit in slowing disease progression. Out of the anti-oxidant products mentioned, only CoQ10 has been run in clinical trials, and it did not meet its clinical endpoints. None of the other supplements have been run in clinical trials. This lack of clinical trial data makes it difficult to make any comparison between Edaravone and other available anti-oxidant products.

• I participated in a year-long trial and the clinic never communicated any results. Is this normal? I was never told if I was on the placebo or the meds.
  • It is not unusual to participate in a clinical trial and not hear about the results. However, if the trial is over you should be able to contact your clinic to see if you were on the placebo or not.

• Why is so much research focused on familial ALS when 90% of people have sporadic ALS?
  • We talk a lot about familial ALS because the genetic mutations involved in ALS can be more easily identified in familial ALS. It is a starting point for ALS research and aids in understanding the complex factors at play in ALS. Any research focused on familial ALS has important implications for sporadic ALS as well. That said, there is a significant amount of preclinical and clinical work being done for sporadic ALS. Most of the ALS clinical trials have nothing to do with familial ALS.

• What are the implications for sporadic ALS if an ASO, aimed at a particular mutation, works?
  • At this time the implications are unclear. ASOs (antisense oligonucleotides) aim to prevent the production of dysfunctional proteins, including SOD1, but studies are still underway. There are reports that misfolded SOD1 aggregates are present in sporadic ALS, so there might be some potential benefit of ASOs in sporadic ALS, but the drug would need to be tested there before we assume its efficacy.

• Are people who have been diagnosed with a profound autoimmune disease, such as Sarcoidosis, at higher risk of developing ALS?
  • There is anecdotal evidence that a history of autoimmunity in families may correlate with an increased incidence of neurodegenerative disease.

• How far are we from the development of a personalized therapy in ALS? In particular, regarding the possibility to enroll patients in clinical trials on the basis of their genomic profile. For example, in the case of the tested drug AMX0035, are clinical trials stratified taking into account of their mitochondrial deficit (also at genetic level) or not?
  • We are very close with ASOs targeting genetic forms of the disease, but not very close otherwise.

• Our family has the rare VCP form of ALS. Is there any possibility that treatments for other forms of ALS, such as SOD1, would be usable in VCP treatment? Alternatively, are there any frontotemporal dementia treatments that could be possible candidates?
  • The development of effective treatments for any form of ALS will likely have implications for other forms, including forms that see mutation in the VCP (valosin-containing protein) gene. Drug advancements that focus on one mutation may help to direct drug development pathways for the others. Additionally, it is possible that ASOs could be developed to target the VCP genetic subtype of ALS.

• Can the C9orf72 mutation be treated with Trazodone?
  • Trazodone is a drug that helps to restore the balance of serotonin in the brain to treat depression. There was a recent study that hypothesized that Trazodone might block the production of toxic C90rf72 proteins, but this study has not yet been repeated and there is no clinical data to support Trazodone as a treatment for ALS.

• Any take on Elysium health’s “basis” EH301?
  • The phase 1 trial for EH301, also known as Basis, was completed in January 2019 with only 15 participants, a short 4-month duration, and a 38 percent dropout rate. There is not enough data from this trial to say much.

•  Is there a connection between my ALS and two generations of family with dementia?
  • There are several genetic mutations that can lead to ALS or dementia, or in some cases both.

ALS TDI feels strongly that education and awareness help to empower us all in the fight against ALS. We encourage you to check out the ALS TDI blog for research updates, listen to ALS TDI’s The Endpoints Podcast, or join your local ALS Community. Do you have questions for the next ALS Unfiltered session? Contact Gabrielle Bellitti at GBellitti@als.net.