Entrepreneurial development award for a novel Alzheimer's disease therapeutic

一种新型阿尔茨海默氏病治疗药物获得创业发展奖

基本信息

批准号：
10515571
负责人：
Anne Valat
金额：
$ 40.65万
依托单位：
BOLDEN THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-05 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10515571
关键词：
3xTg-AD mouse Adult Age Aging Agrin Alternative Splicing Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Alzheimer&apos s disease therapeutic Alzheimer&apos s disease therapy Amyloid Animal Model Antisense Oligonucleotides Award Binding Proteins Biotechnology Bone Morphogenetic Proteins Businesses Cells Chemistry Cognition Complement Conduct Clinical Trials Confidential Information Critical Pathways Cultured Cells Dementia Development Disease Dose Drug Kinetics Engineering Entrepreneurship Exhibits FDA approved Fertility Future Hippocampus (Brain)Human In Vitro Incubators Industry Innovation Corps Knock-in Mouse Lead Learning Length Maximum Tolerated Dose Mediating Memory Memory Loss Mentors Modality Modeling Motor Neurons Mus Neurodegenerative Disorders Neurofibrillary Tangles Neuromuscular Junction Pathology Pathway interactions Patient Care Patients Pharmacodynamics Pharmacologic Substance Phase Positioning Attribute Program Development Reporting Research Risk Factors Role Safety Science Scientist Seasons Shapes Signal Pathway Signal Transduction Signaling Protein Spinal Muscular Atrophy TREM2 gene Testing Therapeutic Training Support Transcript United States National Institutes of Health Validation Wild Type Mouse Work age related aged aging population career career development efficacy testing exon skipping experience experimental study improved in vivo in vivo evaluation lead candidate mouse model nerve stem cell nervous system disorder neurogenesis neuron loss newborn neuron normal aging novel novel strategies novel therapeutic intervention pre-clinical preclinical development prevent programs receptor safety study screening skills success tau Proteins therapeutic development therapeutic target therapy development

项目摘要

The aging population in the US and globally has led to an urgent need for therapeutics to prevent and treat Alzheimer's disease (AD). Adult Hippocampal Neurogenesis (AHN) is critical for normal learning and memory and declines in patients with AD. Work in animal models has underscored the role of AHN in improving cognition in the face of AD pathology. Thus, restoring AHN has emerged as an attractive target for an AD therapy. Bolden Therapeutics has discovered a new pathway to promote AHN. Critically, this pathway can be targeted by exon-skipping antisense oligonucleotides (ASOs), a therapeutic modality that is on the market and has emerged as effective and safe for regulating alternative splicing in the CNS. Dr. Valat led the effort to identify several lead ASOs that successfully skip our target region in cultured cells. In this Phase I effort, these ASOs will be tested in vivo. We will evaluate their safety as well as their ability to promote AHN and improve cognition in aging wild-type mice (Aim 1), and in a mouse model with entrenched AD pathology (Aim 2). Evaluating the safety and efficacy of these candidates is a critical step that would support the advancement of these ASOs to IND-enabling experiments and rapid preclinical development. Dr. Valat has extensive experience in the technical and the scientific management of in vitro experiments, as proven by the work that she has done at Bolden Therapeutics in identifying the lead ASOs. In the work proposed she will now take a leading role in directing the key in vivo preclinical phase of therapeutic development - a critical step for any pharmaceutical company. Dr. Valat's entrepreneurial development will be guided by three seasoned co- mentors who bring skills and experience in discovery science, interacting with the FDA, conducting clinical trials, caring for patients, starting companies, business development, fundraising, and investing in novel scientific discoveries. Thus, this award will allow her to transition with success from bench work to an entrepreneurial position. In parallel to this hands-on experience, Dr. Valat will also benefit from a range entrepreneurship and career development programs from LabCentral, a premier biotech incubator where she is currently performing Bolden's research, programs offered by the NIH such as I-Corps, and from an intensive Entrepreneurship Development Program offered at MIT. Overall, this award will complement Dr. Valat's expertise and enable her to advance her skillsets both as a research scientist and as a future leader in the biotechnology industry.

美国和全球人口老龄化导致迫切需要预防和治疗阿尔茨海默病 (AD) 的疗法。成人海马神经发生 (AHN) 对于正常学习和记忆以及 AD 患者的衰退至关重要。动物模型研究强调了 AHN 在改善 AD 病理情况下的认知方面的作用。因此，恢复 AHN 已成为 AD 治疗的一个有吸引力的目标。 Bolden Therapeutics 发现了促进 AHN 的新途径。至关重要的是，该途径可以通过外显子跳跃反义寡核苷酸（ASO）作为目标，这是一种市场上的治疗方式，并且已成为调节中枢神经系统中选择性剪接的有效且安全的方法。 Valat 博士领导了鉴定几个先导 ASO 的工作，这些 ASO 成功地跳过了我们在培养细胞中的目标区域。在第一阶段的工作中，这些 ASO 将在体内进行测试。我们将评估它们的安全性以及它们在衰老野生型小鼠（目标 1）和具有根深蒂固的 AD 病理学的小鼠模型（目标 2）中促进 AHN 和改善认知的能力。评估这些候选药物的安全性和有效性是支持这些 ASO 推进 IND 实验和快速临床前开发的关键一步。 Valat 博士在体外实验的技术和科学管理方面拥有丰富的经验，她在 Bolden Therapeutics 确定领先 ASO 方面所做的工作证明了这一点。在拟议的工作中，她现在将在指导治疗开发的关键体内临床前阶段方面发挥主导作用，这对于任何制药公司来说都是关键的一步。 Valat 博士的创业发展将由三位经验丰富的导师指导，他们带来科学发现、与 FDA 互动、进行临床试验、照顾患者、创办公司、业务发展、筹款和投资新科学发现方面的技能和经验。因此，这个奖项将使她能够从替补工作成功过渡到创业职位。在获得实践经验的同时，Valat 博士还将受益于 LabCentral 的一系列创业和职业发展项目，LabCentral 是一家一流的生物技术孵化器，她目前正在该孵化器中进行 Bolden 的研究，以及 NIH 提供的项目，例如 I-Corps 和来自麻省理工学院提供的强化创业发展计划。总体而言，该奖项将补充 Valat 博士的专业知识，并使她能够提高作为研究科学家和生物技术行业未来领导者的技能。