New and Novel Potential Treatment for Alzheimer Disease Symptom Management

A new modulator of cholinergic neurotransmission, AD101 (AmyriAD Therapeutics, Los Angeles, CA) in combination with the acetylcholinesterase inhibitor (AChEI) donepezil is being evaluated for potential treatment of Alzheimer disease (AD) symptoms. 

Individuals with AD who had been on a stable dose of donezepil for at least 90 days and were treated for 12 weeks with AD101 had statistically significant mean improvement of approximately 2 points on the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). In contrast, individuals who had continuation of donezepil plus placebo had declines on ADAS-Cog (P=.038). Twice as many of those treated with AD101 vs placebo (P=.043) had improvements in independent function on the Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (ACDS-CGIC). 

Sharon L. Rogers, PhD, chief executive officer of AmyriAD noted, "At AmyriAD we understand day-to-day disease management has value and that memories are worth fighting for. We are committed to the development of agents that can improve AD symptoms and patient's quality of life."  She also added, “We are in preparations to launch our phase 3 clinical trial program in the first half of 2023. These trials will include patients across a broad range of disease severity reflecting real-life clinical practice.” 

In phase 2 clinical trials (NCT00842816 and NCT00842673), AD101 was well-tolerated with an effective dose more than tenfold below the dose at which the No Adverse Effect Level (NOAEL) occurred in animal toxicology studies. AD101 is a modulator of transient (T-type) calcium channels found in multiple places within the central nervous system, including presynaptic membranes and, most recently, lysosomal membranes.

At the presynaptic membrane, AD101 modulates the T-type calcium channel to increase calcium ion flux into the presynaptic cell and increase release of the neurotransmitter acetylcholine (ACh). Used with donezepil, which protects acetylcholine from degradation after it is released into the synapse, AD101 has potential to produce additive improvement of memory and other symptoms of AD.