Acumen Pharmaceuticals, Inc — Department of Health and Human Services STTR Phase I: NIA

Description

In the United States in an estimated million people suffered from Alzheimer s disease AD with as many as being undiagnosed Alzheimer s Association Three stages of AD are proposed National Institute on Aging and the Alzheimer s Association preclinical AD mild cognitive impairment MCI due to AD and dementia due to AD The preclinical stage is proposed to begin or more years before symptoms appear Today many researchers believe that treatments to slow or stop AD will be most effective if administered during the preclinical or MIC stages However new biomarker tests are needed to identify individuals at these early stages These biomarker tests will also be essential for monitoring treatment effects Current biomarker tests for AD are based on the levels of total amyloid beta A mainly monomer in cerebrospinal fluid CSF levels of tau and phosphorylated tau in CSF or the levels of fibrillic amyloid plaques in the brain However many researchers now regard non fibrillic A oligomers A o in contrast to monomeric or fibrillic A as the primary A toxins that cause acute cognitive deficits and induce the chronic neuronal degeneration of AD tau abnormalities synapse loss oxidative damage etc A non invasive method to detect and quantify A o could provide a valuable biomarker test to identify early stage AD patients and for monitoring the effect of therapies Preliminary studies suggest that an A o selective antibody positron emission tomography PET probe may enable the in vivo detection and quantification of A o ACU is a proprietary affinity matured humanized monoclonal antibody exhibiting high selectivity for A o versus monomeric and fibrillic A In AD mouse models ACU crosses the blood brain barrier and forms complexes with A o in the brain ACU exhibits excellent pharmacokinetics biodistribution and brain penetration in four animal species Protein binding studies show excellent selectivity for A o Exploratory toxicity studies in monkeys reveal an excellent safety profile for ACU Thus ACU is an ideal candidate for testing the potential utility of an A o antibody PET probe for the in vivo detection and quantification of A o The objective of this Phase STTR application is to prepare and optimize an ACU PET probe and demonstrate that it provides a sensitive and selective in vitro A o dependent signal from transgenic AD mouse model tissues and human AD brain tissues The underlying hypothesis is that a sensitive and highly A o selective PET probe can be made using ACU labeled with Cu If in vitro sensitivity and selectivity are achieved the Phase study will also evaluate the sensitivity of the probe in vivo in a transgenic AD mouse mode Overall success in this program would provide a non invasive method for detecting and quantifying A o in vivo and support its development as an AD diagnostic tool for monitoring disease progression and the effects of treatment and as a research tool that would enable a better understanding of the etiology of AD The proposed research is relevant to public health and the mission of the National Institute on Aging NIA because it is expected to provide a first of its kind Alzheimer s disease PET probe that has broad application for both early stage diagnosis and assessing the experimental efficacy of investigational new drugs Early diagnosis of Alzheimer s disease is crucial for the most effective treatment and is not possible with current technology The PET probes characterized in the proposed research targets toxic amyloid beta oligomers which are biomarkers that develop years before currently measured pathology