A Humanized Monoclonal FSH Blocking Antibody for Alzheimer's Disease

治疗阿尔茨海默病的人源化单克隆 FSH 阻断抗体

基本信息

  • 批准号:
    10279706
  • 负责人:
  • 金额:
    $ 171.26万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-30 至 2026-08-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Alzheimer’s disease (AD) stands out as notable in not having a cure among many diseases that affect elderly men and women––in essence, creating an urgent need for a new therapy. It is also unclear why menopausal women have a preponderance of AD, and, while declining estrogen bas been implicated, there is clear clinical correlation with rising levels of follicle stimulating hormone (FSH). We have identified FSH as a target for several aging disorders––osteoporosis, obesity, hypercholesteremia––and now, AD. Inhibiting the action of FSH using blocking antibodies reduces body fat, increases bone mass, lowers serum cholesterol, and from our newest and most exciting results, prevents AD in two mouse models. We have designed a novel humanized monoclonal antibody, Hu6, that binds to a small epitope within the receptor–binding domain of FSHβ, thus blocking its action on the FSH receptor (FSHR). Our aspirational goal is to use this lead therapeutic for the therapy and prevention of all four disorders––or, at the very least, AD. Selected from a pool of 30 newly synthesized humanized antibodies, Hu6 displays high–affinity binding to FSH (KD ~7 nM) and thus prevents its action on hippocampal FSHRs to improve cognition in AD mice. These observations, together with its optimal pharmacokinetic profile, lay the groundwork for Hu6 to enter early stage development. In Specific Aim 1, we propose to scale up production of research–grade Hu6; create an optimal formulation; test its physicochemical properties; study the structure of the FSH:Hu6 complex; and manufacture a master cell bank for cGMP–grade Hu6. In Specific Aim 2, we will perform pharmacokinetic studies in Tg32 mice ‘humanized’ for antibody clearance, and in African green vervet monkeys; determine minimum effective dose(s) in preventing and/or treating AD in 3xTg mice; examine efficacy and safety in young and aged 3xTg mice; and document safety in vervet monkeys. The work will be conducted using Good Laboratory Practice (GLP) standards established at Mount Sinai, Emory, Wake Forest and San Antonio. We have also created cross–functional research teams that will be supported by a distinguished panel of advisors, comprising science and medicine experts, business leaders, and entrepreneurs in biotechnology. Definitive information on dosage, route and frequency, together with early proof of safety should propel us into late stage development and first–in–human studies.
项目总结

项目成果

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Tony Yuen其他文献

Tony Yuen的其他文献

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{{ truncateString('Tony Yuen', 18)}}的其他基金

A Humanized Monoclonal FSH Blocking Antibody for Alzheimer's Disease
治疗阿尔茨海默病的人源化单克隆 FSH 阻断抗体
  • 批准号:
    10693288
  • 财政年份:
    2021
  • 资助金额:
    $ 171.26万
  • 项目类别:

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