Validation in Drosophila of the in silico predicted clomipramine as repurposable for SOD1-ALS
Francesco Liguori, Susanna Amadio, Chiara Angioli, Angelo Ferriero, Iolanda Passaro, Francesca Alberti, Fiammetta Vernì, Cinzia Volonté
TL;DR
This study validates clomipramine as a potential treatment for SOD1-related ALS using fruit fly models, showing improved lifespan and reduced disease markers.
Contribution
The novel contribution is the experimental validation of in silico drug repurposing predictions in a Drosophila model of SOD1-ALS.
Findings
Clomipramine improved lifespan and climbing abilities in Drosophila SOD1-ALS models.
The drug mitigated genomic instability and inflammation in these models.
Clomipramine outperformed other tested compounds like mianserin and modafinil.
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive motor neuron degeneration and muscle weakness, generally leading to death due to respiratory failure within 2–5 years of symptom onset. Current Food and Drug Administration-approved drugs —riluzole, edaravone, and tofersen — offer limited clinical benefit due to ALS multifactorial etiology and high heterogeneity. To bypass this therapeutic letdown, we previously exploited network medicine and drug repurposing strategies. Leveraging the SAveRUNNER algorithm, we identified several potentially repurposable candidates, including clomipramine (Anafranil®), mianserin (Lantanon®/Tolvon®), and modafinil (Provigil®). Here, we evaluated the in vivo efficacy of these compounds in Drosophila models of ALS, precisely those expressing pan-neuronal human SOD1A4V or SOD1G85R mutations. Our…
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Taxonomy
TopicsAmyotrophic Lateral Sclerosis Research · Genetic Neurodegenerative Diseases · Neurogenetic and Muscular Disorders Research