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While the general role of amyloid β (Aβ) is well known in Alzheimer’s disease (AD), Aβ is complex and aggregates into different and unpredictable forms. A singular Aβ peptide is referred to as a Monomer. In abnormal concentrations, Aβ monomers join together into aggregates which can be categorized, respectively by average size, as Soluble Oligomers (oAβ), Soluble Protofibrils, and Insoluble Plaques (Plaque). Research has shown that Soluble Oligomers are much more toxic than other forms of Aβ, yet therapeutic interventions to-date have largely focused on Monomers and Plaque. Targeting Plaque has shown significant adverse effects (brain swelling and bleeding) and questionable efficacy in clinical trials, while targeting Monomers has outright failed. There is an urgent need for therapeutics that target oAβ, while avoiding the other forms of amyloid associated with negative side effects and decreased efficacy.
In recognition of this, Abyssinia is developing a new generation of antibody therapeutics with this profile in mind. These antibodies are designed to preferentially bind small toxic Aβ oligomers while minimizing off target binding which we believe will lead to increased efficacy and improved safety.
The de-facto diagnostic tools for AD function by quantifying Insoluble Plaque as this is the most easily detected hallmark of AD. But quantifying Plaque load is both expensive and has failed to serve as an effective differentiator of disease status or progression. In one study, 43% of cognitively normal adults aged 80-89 had AD positive levels of plaque in their brains. Scalable, affordable, and convenient diagnostics that specifically measure oAβ will likely enable better patient selection and evaluation in clinical trials, clinical practice, and reimbursement.
Abyssinia has partnered with the world renowned Selkoe Lab at Brigham and Women’s Hospital to design a diagnostic assay that uniquely and precisely quantifies oAβ in blood and cerebrospinal fluid (CSF). This assay is being retrospectively evaluated in large cohorts of banked samples from academic and clinical collaborators.