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It’s complicated: benefits and toxicity of anti-prion antibodies in the brain

Immunotherapy to ameliorate neurodegeneration by targeting brain protein aggregates with antibodies is an area of intense investigation. A study published in PLOS Pathogens examines seemingly contradictory earlier results of targeting the prion protein and proposes a cautionary way forward to further test related therapeutic approaches.

Damaging aggregation of proteins in the brain is a hallmark of several neurodegenerative diseases, including Alzheimer and Parkinson diseases. In prion diseases such as Creutzfeld-Jakob disease, aggregates of abnormally folded versions of the PrP protein cause the death of brain cells. The use of anti-PrP antibodies to target such aggregates and mediate their destruction by the immune system has been proposed as a therapy, with the caveat that such antibodies could themselves be toxic.

3D surface representation of the prion protein
3D surface representation of the prion protein. The areas rendered in color illustrate the interaction with the two neurotoxic antibodies, POM1 and ICSM18
Image Credit: Reimann et al.