SCA Therapeutics Development

This page lists some therapeutics (mostly drugs; indexed by company) being developed for spinocerebellar ataxia (SCA) and Huntington’s disease (HD). For SCA, the first batch of pharmaceuticals reasonably make no claims to stop or prevent the disease. What’s notable is that it’s the first batch of pharmaceuticals that have gone clinical for SCA.

Why include Huntington’s disease?

The SCA that I have (SCA3) and HD both are polyglutamine diseases, and gene-based therapeutics for one can likely be stepping stones for the other. HD prevalence is higher than SCA prevalence and a worse disease, so it’s usually given higher priority. Polyglutamine-SCA therapeutics are quite literally waiting for success first with HD before attempts are made to ride on its coattails.

How different is Friedreich’s ataxia?

Friedreich’s ataxia (FA) and SCA(3) are very different diseases. Will there be leverage between therapeutics, like I assume there will be for polyglutamine diseases such as HD and SCA(3)?

  • Since FA is autosomal recessive, the inheritance pattern is completely different from SCA. Also, FA comes on stronger and is fatal to children.
  • The prevalence of FA is about the same as all the SCAs combined. There are at least a dozen pharmaceutical companies working on therapies for FA but only a small handful working on SCA.
  • The genetic defect that causes SCA(3) is in an exon and causes a ubiquitous protein to be toxic primarily to the cerebellum. The genetic defect that causes FA is in an intron and causes a protein to not be created that is needed in various areas of the body.
  • Because of the exon/intron situation, SCA(3) can be modified at the DNA or RNA level, but FA can be modified at the DNA level but not the RNA level.
  • There are no gene therapy approaches that will work for both. Though some believe CRISPR/Cas9 will be able to repair billions of mature neurons, I’m more skeptical.
  • Therapeutic approaches to each disease that don’t involve gene therapy tend to be entirely unrelated.


See here for a general description of trial phases.

From this PDF, the overall probability of success was 63% in phase 1 trials, 31% in phase 2 trials, 58% in phase 3 trials and 85% during the regulatory review process, for an overall success rate (phase 1 to approval) of 9.6% (63% × 31% × 58% × 85% = 9.6%). The success rate of going from phase 2 to approval  was 15% (three make it, and seventeen don’t).

The following lists are alphabetical.

Specific to SCA or SCA3

Bioblast Pharma Ltd.

  • Pipeline [find with Google]
  • Therapeutic for SCA3
    • Code name: Cabaletta.
    • Generic name: trehalose, a disaccharide in the same family as table sugar (sucrose).
    • Administration: intravenous.
    • Described by Bioblast as a mutant protein stabilizer.
    • Described here as an autophagy enhancer.
    • General goal: slow cerebellar degeneration. No claims are made about stopping or preventing the disease.
    • Stage in 2017-November: phase 2a successful and complete in Israel (link below).
  • Find with Google: Bioblast and ataxia

Bioblast published positive phase 2a trial results on 2017-01-18: SCA3 progression did not worsen in 14 people after 6 months nor in 5 people after 12 months.

Bioblast has spent most of 2017 in financial trouble, seeking partnership or merger opportunities. The company is using JSB Partners to assist in business development. Details as of 2017-11-02.

2018-01-04: Trehalose has been dominating the news with how it might be proliferating some fatal superbugs.

Biohaven Pharmaceutical

  • Pipeline [find with Google]
  • Drug for SCA
    • Code name: BHV-4157 (link goes to my own assessment).
    • Generic name: trigriluzole (link goes to my own assessment).
    • Administration: by mouth.
    • Mechanism of action: reduces glutamate in the brain.
    • General goal: slow cerebellar degeneration by reducing needless excitement of neurons.  No claims are made about stopping or preventing the disease.
    • Stage in 2017-November: phase 2 failed in the U.S.
  • Find with Google: Biohaven and ataxia

Cadent Therapeutics

  • Pipeline [find with Google]
  • Drug for SCA and essential tremor (ET):
    • Code name: CAD-1883.
    • I think the and is important. This seems to be for people with SCA and ET, or perhaps ET caused by SCA. Their website uses about 3,200 per 100,000 in the U.S. as having ET and 2 per 100,000 in the world (6,500 in the U.S.) as having SCA. Presumably those with SCA have a higher ET prevalence, but the combination must be quite small—hundreds of people, maybe breaking a thousand in the U.S.
    • Good term to know: SK channel.
    • Allosteric activator: improves regulation of brain activity to help restore motor and cognitive function.
    • No claims are made about this being an SCA disease modifier; rather, this is symptom relief.
    • 2017-10-17: expected transition to clinical phase in 2018.
    • 2018-03-12: transition to phase 1. Also announced a partnership with Saniona.
    • Possibly related to (in competition with) Cavion and their CX-8998 product.
  • Find with Google: Cadent and ataxia

Shionogi & Co., Inc.

  • Pipeline [find with Google]
  • Drug for SCA
    • Code name: S-0373, or KPS-0373 at partner Kissei Pharmaceuticals
    • Generic name: rovatirelin.
    • Non-peptide mimetic of thyrotropin-releasing hormone (TRH)
      • Mimetic: essentially an imitation. In other words, it’s synthetic TRH.
      • TRH is now available as a pharmaceutical called protirelin.
    • TRH is thought to improve neurologic dysfunction by improving cerebral blood flow. The effect is temporary and does not stop or prevent the disease.
    • Stage in 2018-February: phase 3 in Japan. But it appears to have been in phase 3 since at least 2014; it was in phase 1 in 2006; kind of mysterious.
    • Just guessing: possibly a follow-on of some sort to taltirelin, approved in Japan in 2000 as an SCA therapeutic—the first ever, I think.
  • Find with Google:

Specific to Huntington’s disease, but with SCA(3) in the pipeline

Vybion, Inc

Wave Life Sciences

Specific to Huntington’s disease

Ionis Pharmaceuticals, Inc.


Huntington’s disease, preclinical

Sangamo Therapeutics, Inc.

Spark Therapeutics



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