An oral small molecule from New York-based biotech Oligomerix curbed the tangling of tau protein in the brains of mice that model a rare neurological disease.
The results, published on March 12 in the Journal of Neurochemistry, suggest that OLX-07010 could be a viable treatment for tau-related diseases, a category that includes Alzheimer’s disease (AD).
Oligomerix researchers, led by chief scientific officer Eliot Davidowitz, Ph.D., had previously found that OLX-07010 prevented tau from aggregating in mice genetically predisposed to develop tau tangles. In the current study, they focused instead on mice that already had tau aggregations in their brains, finding that treatment with the molecule reduced the amount of the harmful bundles compared to the results seen in untreated mice.
In addition to reducing tangles, treated mice were also able to balance on a rotating rod for longer than untreated mice, a common test of motor coordination.
“This study shows that treatment of mice with pre-existing tau aggregates with OLX-07010 can block the further accumulation of tau aggregates,” William Erhardt, M.D., Oligomerix’s president and head of development, said in a March 12 release. “This is important for Alzheimer’s patients because the progression of tau aggregation begins years before clinical symptoms are apparent.”
Tau protein plays a vital role in the brain, helping to stabilize neurons. But in some cases, the protein can get sticky with itself, bunching together into aggregations that lead to neurological diseases called tauopathies. The mice used in this study had mutated forms of tau similar to those seen in progressive supranuclear palsy, a rare tauopathy that causes problems with speech, coordination and cognitive functions like memory.
In contrast, the study authors note, tau is not mutated in AD, which means future work is needed to see how mice with Alzheimer’s-like tangles respond to OLX-07010. Alzheimer’s is thought to be driven by the aggregation of two types of proteins, tau and amyloid beta.
“It is anticipated that drugs targeting amyloid beta aggregates, considered an initiating factor for AD, with drugs targeting tau and inflammation, involved in disease progression, should have a synergistic effect for treating AD,” Erhardt said.
OLX-07010 is currently being tested in a phase 1 trial of healthy, elderly volunteers, Oligomerix said in the release, with the first doses given in February 2023 according to an earlier release (PDF). The firm expects the trial to be completed this year.