New Drug Target Identified for ALS Treatment

Overview of Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by the gradual deterioration of neuromuscular function. Research has linked several genes to the disease’s onset. A key protein involved is SOD1, which tends to misfold when mutated, leading to toxic accumulation in ALS patients.

Research Findings from the University of Alberta

Researchers at the University of Alberta in Canada have published a study in the journal Neurobiology of Disease, unveiling a promising drug target for ALS treatment. They discovered a specific tryptophan residue on the SOD1 protein that, when mutated, contributes to its misfolding. In experiments using zebrafish models, substituting this residue with a different amino acid resulted in fewer motor deficits compared to zebrafish carrying the mutated SOD1 gene alone.

Screening for Effective Compounds

The team employed computer simulations to identify compounds that could effectively target the newly identified residue. Among the shortlisted candidates, telbivudine was chosen due to its favorable safety profile and its ability to penetrate the blood-brain barrier—a significant challenge in drug delivery for neurological conditions. The study revealed that administering telbivudine significantly decreased SOD1 toxicity in the zebrafish models with the mutated SOD1 gene.

Advantages of Telbivudine

Telbivudine is already approved for treating hepatitis, which provides it with a well-established safety profile, offering a distinct advantage over less familiar compounds. The researchers are optimistic that this existing approval could facilitate its expedited use for ALS treatment, and they advocate for further studies to explore this potential.

References

DuVal MG, Hinge VK, Snyder N, Kanyo R, Bratvold J, Pokrishevsky E, Cashman NR, Blinov N, Kovalenko A, Allison WT. Tryptophan 32 mediates SOD1 toxicity in a in vivo motor neuron model of ALS and is a promising target for small molecule therapeutics. Neurobiol Dis. 2018 Dec 4;124:297-310. doi: 10.1016/j.nbd.2018.11.025. [Epub ahead of print]
Willis, Kate. Biologists identify promising drug for ALS treatment. University of Alberta. 2018 Dec 17. https://www.ualberta.ca/science/science-news/2018/december/als-treatment-promising-drug