Tübingen researchers cut toxic SCA3 protein by 90% in lab-grown human neurons
Researchers from DZNE and the Hertie Institute for Clinical Brain Research at the University of Tübingen, with collaborators in Bonn, London and Portugal, tested antisense drugs designed to target the disease-causing copy of the SCA3 gene. In human neurons cultured in the lab, the most effective drug reduced toxic ataxin-3 by about 90% while largely preserving the normal protein, according to the study published in Science Translational Medicine.
Bottom line — The team says it will optimise the drugs and test their safety and efficacy in further studies before considering clinical trials.
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SCA3, also called Machado-Joseph disease, can affect walking, speech and eye movements, according to DZNE.
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The researchers analysed genetic data from 79 people with SCA3 to identify small differences between the disease-causing gene copy and the healthy copy.
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The antisense drugs bind to messenger RNA carrying instructions from the disease-causing gene, prompting its breakdown, the researchers explain.
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The researchers say earlier antisense approaches could also reduce healthy ataxin-3; their design aims to spare it.
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The findings are preclinical: the researchers tested the approach in lab-grown human neurons, not in patients.