|Title||Viral-mediated delivery of antibody targeting TAR DNA-binding protein 43 mitigates associated neuropathology.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Pozzi, Silvia, Sai Sampath Thammisetty, Philippe Codron, Reza Rahimian, Karine V. Plourde, Geneviève Soucy, Christine Bareil, Daniel Phaneuf, Jasna Kriz, Claude Gravel, and Jean-Pierre Julien|
|Journal||J Clin Invest|
|Date Published||2019 Jan 22|
The cytoplasmic aggregation of TDP-43 is a hallmark of degenerating neurons in amyotrophic lateral sclerosis (ALS) and subsets of frontotemporal dementia (FTD). In order to reduce TDP-43 pathology, we have generated single chain (scFv) antibodies against the RNA recognition motif 1 (RRM1) of TDP-43 which is involved in abnormal protein self-aggregation and interaction with p65 nuclear factor kappa B (NFKB). Viral-mediated delivery into the nervous system of a scFv antibody, named VH7Vk9, reduced microgliosis in a mouse model of acute neuroinflammation and it mitigated cognitive impairment, motor defects, TDP-43 proteinopathy and neuroinflammation in transgenic mice expressing ALS-linked TDP-43 mutations. These results suggest that antibodies targeting the RRM1 domain of TDP-43 might provide new therapeutic avenues for treatment of ALS and FTD.
|Alternate Journal||J. Clin. Invest.|