Therapy Approved for Parkinson’s Has Potential to Treat ALS, Preclinical Study Suggests

Therapy Approved for Parkinson’s Has Potential to Treat ALS, Preclinical Study Suggests

Requip (ropinirole), a medication already approved to treat Parkinson’s disease, may be a potential therapeutic agent for amyotrophic lateral sclerosis (ALS), according to a preclinical study.

The study, “Modeling sporadic ALS in iPSC-derived motor neurons identifies a potential therapeutic agent,” was published in the journal Nature Medicine.

Most cases of ALS (90-95%) are considered to be sporadic, with only 5-10% of cases inherited, or familial. The sporadic nature of the majority of cases of ALS makes it difficult to create models of the disease, and to identify disease-causing genes and potential therapeutic compounds.

As a result, while a dozen mutations have been shown to cause familial ALS, such as in the SOD1, TDP-43, and FUS genes, the causes of sporadic ALS are largely unknown.

However, increasing evidence has pointed to the existence of several common features between sporadic ALS and non-SOD1 familial ALS — such as those affecting the TDP-43 or FUS genes — suggesting that compounds suppressing these common features may represent new therapeutic agents for a wide range of ALS patients.

Japanese researchers evaluated the therapeutic effects of selected compounds in a variety of ALS cases through the establishment of sporadic ALS models.

They generated motor nerve cells from induced pluripotent stem cells (iPSCs) — stem cells derived from differentiated cells that can virtually generate any cell type in the body — of 32 sporadic ALS patients.

These cells were able to mimic the patients’ genetic and clinical diversity in vitro, making them successful cellular models of sporadic ALS.

“We clearly demonstrated that iPSC technology enabled the generation of elaborate disease models that accurately reflect the clinical features of genetic conditions, even sporadic diseases,” the researchers wrote.

An analysis of the therapeutic effects of more than 1,000 approved medications in non-SOD1 familial ALS models, as well as the compounds’ serious side effects and ability to cross the blood-brain barrier — a protective membrane that restricts the passage of large molecules to the brain — pointed at Requip as the best potential therapeutic agent.

Requip, an anti-Parkinson’s medication, acts as a substitute for dopamine in the brain. Dopamine is an essential chemical messenger between nerve cells that recent studies have suggested is a regulator of motor nerve cell function.

Adding Requip to the sporadic ALS models was found to suppress cell death, abnormal protein aggregation, nerve cell atrophy, and the production of oxygen-related damaging molecules in most of the models.

While the majority of the sporadic models that responded to Requip showed similar features to TDP-43– and FUS-familial ALS models, those that did not respond had a gene expression profile more similar to SOD1-familial ALS models — which were also non-responders.

These findings highlight the potential of Requip to treat a diverse range of ALS cases, both familial and sporadic.

Additional analysis of the changes in gene activity induced by Requip showed the involvement of inflammation — fat degradation — and dopamine-related pathways.

These results support the use of this approach to generate sporadic ALS models, better understand the mechanisms behind specific cases of ALS, and identify new therapy candidates.

The team noted that this approach may be applied to other sporadic neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease.

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  1. Ida M Halasz says:

    Great to know! Gives me hope.
    1. Can this drug be prescribed for ALS now?
    2. Does this drug interfere with Radicava and Riluzole?
    Thank you.

  2. Agentjoe72 says:

    I am not a chemist, but it seems that Requip (C16H24N2O) also acts like ibudilast (C14H18N2O). The advantage would be that Requip is already allowed.

  3. SCHMIT Joël says:

    Je prend du ” Sifrol ” médicament contre la maladie de Parkinson, moi c’est pour la maladie des jambes sans repos

    Je le prend depuis plusieurs années et malgré cela ma SLA continue sa progression, pourtant le ” Sifrol ” a les mêmes propriétés que le ” Requip “

  4. Stemer j says:

    Bonjour ! Qui peut demander à l’universite Japonaise ce qu’ elle suggère comme dose quotidienne de Requip pour les essais cliniques qui auront lieu sans doute bientôt Merci js

  5. Christie Fairchild says:

    I have been recently diagnosed with ALS after a year of wondering and worrying. it is, of course, devastating. My question right now has to do with my father, who died in 1998. He had ATYPICAL Parkinsons and it took him very quickly(5 years). Could my ALS be connected genetically? And if so, would any of the new Parkinson’s therapies/meds be useful for me? (The dopamine replacement did nothing for him, however) Thank you for your time.

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