Research has shown that approximately 97% of people with ALS have toxic clusters of a protein called TDP-43 in brain and spinal cord cells.* Scientists do not know exactly why TDP-43 proteins clump together, but these clusters are toxic and can lead to death of cells in the brain and spinal cord.
In addition, another protein called ataxin-2 (ATXN2) is thought to be involved in clumping TDP-43 proteins together, helping form these toxic TDP-43 clusters.
*Ling SC, Polymenidou M, Cleveland DW. Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron. 2013;79(3):416-38.
TDP-43 is a protein that normally serves many roles in the cell.
Hart MP, Gitler AD. “ALS-associated ataxin 2 polyQ expansions enhance stress-induced caspase 3 activation and increase TDP-43 pathological modifications.” J Neurosci. 2012 Jul 4;32(27):9133-42. doi: 10.1523/JNEUROSCI.0996-12.2012. PMID: 22764223; PMCID: PMC3418890.
What questions are researchers looking to answer?
Researchers are looking to evaluate the safety and tolerability of the investigational drug, BIIB105, in people with ALS, with or without polyQ-ALS. The researchers will also look at what the body does to BIIB105, what BIIB105 does to the body, and if BIIB105 can slow the worsening of clinical function.