Researchers may be one step closer to developing a potential immunotherapy for ALS. The approach, developed by ProMIS Neurosciences in Toronto, Canada, aims to reduce motor neuron toxicity in ALS by removing TDP-43 aggregates, which clutter up the cytoplasm.
Clear out. Potential immunotherapies aim to protect motor neurons in ALS by reducing the build-up of TDP-43 in the cytoplasm. [Image: TDP-43 inclusions (arrows) in sALS. Courtesy of Taylor et al, 2016, Nature.]
The researchers, according to ProMIS Neurosciences, generated monoclonal antibodies that specifically detect misfolded TDP-43. Now, the team is testing these antibodies to identify the most promising candidate to develop as a potential therapy for the disease.
The strategy is one of a growing number of approaches that aims to protect motor neurons in ALS by reducing the build-up of TDP-43 in the cytoplasm (see September 2017 news). TDP-43 aggregates can be detected in the cytoplasm of motor neurons in more than 95% of cases of the disease (Mackenzie et al., 2007).
Meanwhile, in Japan, researchers are developing a different approach in hopes to reduce motor neuron toxicity in ALS. The strategy, developed by a research team led by Shiga University of Medical Science’s Makoto Urushitani, uses single-chain antibodies, known as intrabodies, to target the aggregates for destruction (Tamaki et al., 2018). The intrabodies, which are encoded by a single gene, can be packaged into adeno-associated viruses (AAVs), enabling delivery into motor neurons and glia in the brain and spinal cord (see June 2017, July 2017 news). Stay tuned.