As published today in the Journal of Alzheimer’s Disease, a new oral small molecule drug (Oligomerix, Bronx, NY) has been shown, in the htau mouse, to inhibit formation of neurotoxic tau oligomers. The htau mouse expresses all 6 isoforms of tau found in humans and is a well-known model of tau pathology seen in Alzheimer’s disease (AD).
Of note, this new compound blocked tau self-association, the earliest known step in the toxic tau aggregation cascade and formation of toxic tau fibrils was also prevented. Levels of insoluble tau aggregates and phosphorylated insoluble tau aggregates were decreased in a linear, dose-dependent manner. Immunocytochemical analysis showed decreased accumulation of misfolded tau associated with tau aggregates.
Mice were administered the tau aggregation inhibitor at 3 different doses in their feed, and no adverse events or behavior abnormalities were observed.
Studies are also being done in the JNPL3 mouse model of frontotemporal dementia (FTD), which is tauopathy associated with the human P301L mutation in which the tau 4R0N isoform is expressed.
“This study validates Oligomerix’s approach for inhibiting tau aggregation and shows that targeting tau oligomer formation at the beginning of the aggregation cascade can inhibit the entire downstream aggregation pathway,” commented James Moe, PhD, MBA, president and CEO of Oligomerix, and a coauthor on the publication.
“There is an urgent need for new approaches to the treatment of AD, and this study describes promising results with a novel compound,” said Peter Davies, PhD, director of the Litwin-Zucker Center for Alzheimer’s Disease & Memory Disorders at the Feinstein Institutes, also a coauthor of the publication.
Dr. Moe said, “Our next steps will include studies to assess whether this lead compound might be beneficial in an inherited form of tauopathy, and whether it can ameliorate behavioral defects.”