Hoth, Washington University Plan Preclinical Dosing Tests of HT-ALZ
Hoth Therapeutics and Washington University have agreed to extend preclinical research into HT-ALZ, Hoth’s experimental therapy for Alzheimer’s disease.
Research findings are expected to be helpful in estimating the best dose of HT-ALZ to test in potential clinical trials, according to a company press release.
Hoth entered into a sponsored research agreement with Washington University in June 2021. Initial work was led by two scientists at the Missouri university’s School of Medicine: Carla Yuede, PhD, an associate professor of psychiatry, and John Cirrito, PhD, an associate professor of neurology.
The scientists evaluated the effects of HT-ALS administered orally to aged APP/PS1+/- mice — a mouse model where the animals are genetically engineered to carry two different mutations that are associated with early-onset Alzheimer’s in people.
According to Hoth, results from these initial tests suggested that treatment with HT-ALS lowered levels of amyloid-beta plaques, the irregular clumps of proteins characteristically found in the brains of people with Alzheimer’s and thought to drive the disease. These plaques are reported to affect communication between nerve cells in the brain and to trigger an inflammatory immune response, both of which damage and kill nerve cells.
Reductions in amyloid-beta plaques were reported to be evident in both male and female mice, and plaque levels were reduced compared both with mice given a placebo and with pre-treatment, or baseline levels, in treated mice. These findings suggest that “HT-ALZ has the potential to modify [amyloid-beta] plaque formation in the brain and be developed as an [Alzheimer’s disease] therapeutic,” according to Hoth.
The two parties’ initial research agreement has been extended to further evaluate HT-ALZ’s effects, at varying doses, in Alzheimer’s mouse models. Work will continue to be led by Yuede and Cirrito.
Specifically, planned work will evaluate whether treatment with HT-ALZ can improve measures of learning and memory in APP/PS1 mice. The mice will be treated over time prior to undergoing a battery of behavioral assessments, and researchers will evaluate a range of doses with an aim of determining whether and how different doses of HT-ALZ affect behavior.
“The outcome of these studies is to estimate a human equivalent dose for initiating clinical trials for HT-ALZ,” Hoth stated in its release.