Snapshot: What is Riluzole?

Riluzole, often sold under the trade name Rilutek, is a medication used for the treatment of amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease that mainly affects neurons controlling muscle movements. The drug was approved by the FDA (1995), Health Canada (1997), and the European Commission (1996). It helps slow down disease progression and may extend patient survival. The medication is available in tablet and liquid form, generally well-tolerated. There are sometimes mild side effects, which may include loss of appetite, nausea, and abdominal pain.

Close up of a woman taking a pill with water
Riluzole has been used to treat ALS, and research has suggested it may also help with forms of ataxia. It is currently being tested in clinical trials. Photo used under license by fizkes/Shutterstock.com.

How does it work?

Exactly how Riluzole slows disease progression remains unknown. However, it is thought that its neuroprotective effects likely stem from reducing a phenomenon known as excitotoxicity.

Neurons communicate with each other through chemical messengers called neurotransmitters. The signalling of these messengers needs to be tightly controlled. Too little or too much signaling will disrupt normal functions of the brain and cause damage to cells. Excitotoxicity is the result of excessive signaling by glutamate, one of the most abundant neurotransmitters in the brain. Glutamate is also associated with many neurodegenerative diseases.

Riluzole prevents this excessive signaling through several mechanisms. It is hypothesized that the effectiveness of riluzole in ALS treatment is the result of this neuroprotective property.

Riluzole for Ataxia

The neuroprotective function of riluzole has been a point of interest for the treatment of other neurodegenerative diseases since its approval. Multiple clinical trials have been conducted for patients with neurodegenerative diseases including Parkinson’s disease, Huntington’s disease, multiple system atrophy, and ataxia.

In 2010, a pilot trial was conducted with 40 patients with cerebellar ataxia who showed a lower level of motor impairment, measured by the International Cooperative Ataxia Rating Scale. A follow-up trial was then performed in 2015 for 55 patients with spinocerebellar ataxia (SCA) or Friedreich’s ataxia. Similarly, patient impairment had improved by an alternative measurement using the Scale for the Assessment and Rating of Ataxia. These findings indicate the possibility of riluzole being an effective treatment for cerebellar ataxia. However, more long-term studies and ones that are specific to different types of SCA need to be conducted to confirm the results.

Riluzole in Development

Even though riluzole was discovered more than 25 years ago, variations of the drug are still under development. As ALS often affects a patient’s ability to swallow, a new formulation of riluzole that is absorbed by placing it under your tongue is being developed under the name Nurtec.

Another prodrug version of riluzole, named Troriluzole (BHV-4157), may be better absorbed by the body with fewer side effects. Troriluzole is currently in phase three clinical trial for patients with different types of SCA. The trial is expected to be complete by November 30, 2021, and will hopefully provide more insight into the effectiveness of Troriluzole in SCA patients.

If you would like to learn more about Riluzole, take a look at these resources by the ClinicalTrials.gov and the Mayo Clinic.

Snapshot written by Christina (Yi) Peng and edited by Terry Suk.

Repeat interruptions are associated with epileptic seizures in SCA10

Written by Dr Hannah Shorrock  Edited by Larissa Nitschke

Repeat interruptions in SCA10 influence repeat tract stability and are associated with epileptic seizures

Multiple spinocerebellar ataxias (SCAs) are caused by repeat expansion mutations, but in some cases, these repeat expansions are interrupted. The presence of repeat interruptions can influence disease symptoms and how the repeat expansion behaves. This is the case for SCA10. Some patients with SCA10 have a series of repeat interruptions, which are referred to as an ATCCT repeat interruption motif. In SCA10 patients with this interruption motif, Dr. Ashizawa and his team found an increased risk of developing epileptic seizures and identified that the interruptions influence the local stability of the repeat expansion.

A cartoon of a DNA molecule with light radiating from it
Small interruptions in the ATXN10 gene may affect the likelihood of SCA10 patients developing epileptic seizures

SCA10 is a dominantly inherited ataxia caused by an ATTCT repeat expansion in the Ataxin 10 gene (ATXN10). Unaffected individuals usually carry 9-32 ATTCT repeats, while SCA10 patients carry an expansion of up to 4500 repeats. SCA10 patients suffer from cerebellar ataxia, but some patients also have other symptoms, including epileptic seizures. Dr. Ashizawa and his team were interested in why some patients with SCA10 suffer from epileptic seizures, but others do not.

Initially, the group investigated whether the length of the ATXN10 repeat expansion correlated with epileptic seizures. They found no difference in repeat length between 37 SCA10 patients who developed epilepsy and 51 who did not. This shows that repeat length does not influence whether or not SCA10 patients develop epileptic seizures.

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