Acumen presents in vitro human neuron model for evaluating oligomers in AD

Acumen Pharmaceuticals has demonstrated the utility of a human in vitro model of iPSC-derived excitatory neurons for a better understanding of which forms of amyloid beta oligomers contribute to the pathogenesis of AD in the human brain. This research will be presented in a poster at the International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders AD/PD , held in-person in Gothenburg, Sweden, and virtually March 28 – April 1. There is considerable scientific evidence that supports the role of toxic forms of soluble aggregates of Ass, such as oligomers and protofibrils, in the pathogenesis of AD. Soluble AssOs have been found to bind at synapses, which leads to altered neuronal function, and can initiate and perpetuate the process of neurodegeneration. However, soluble AssOs exist in many forms – including globular and linear conformations, a wide range of size distributions, and diverse epitope displays – and it remains unclear which of these species are most relevant to AD pathogenesis. Soluble AssOs have been challenging to model in the laboratory even though they have been identified in the cerebrospinal fluid of AD patients; their concentrations are low in CSF, and an understanding of their diversity, especially with regard to molecular weights in the human brain, needs additional refinement…This research complements Acumen’s ongoing clinical development of ACU193, a humanized monoclonal antibody candidate that selectively targets toxic globular sAssOs. Acumen recently completed patient enrollment in INTERCEPT-AD, a Phase 1, U.S.-based, multi-center, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and tolerability, and establishing clinical proof of mechanism, of ACU193 in patients with early AD. The Company plans to initiate a Phase 2 trial of ACU193 with the potential to expand into a Phase 3 trial. "We believe that these research efforts contribute to the development of next-generation therapies with higher selectivity for toxic soluble amyloid species that are most relevant to Alzheimer’s pathogenesis," said Erika Cline, Ph.D., lead author and Manager of Bioanalytical Methods at Acumen Pharmaceuticals. "Studies assessing how different soluble AssO species bind to synapses are important for identifying AssO preparations that will help bridge the understanding of how AssO-targeting antibodies behave in biochemical assays and in vivo. Furthermore, models utilizing human neurons have the potential to accelerate the identification of prime targets for clinical drug development. Together with Acumen’s ongoing Phase 1 clinical trial of ACU193, we aim to provide proof of mechanism data that we believe will shed additional light on the role of toxic oligomeric species in Alzheimer’s disease."