Entrepreneurial development award for a novel Alzheimer's disease therapeutic

美国和全球人口老龄化导致迫切需要治疗阿尔茨海默病（AD）的治疗方法。成人海马神经发生（AHN）对阿尔茨海默病患者的正常学习和记忆以及衰退至关重要。动物模型的研究强调了AHN在面对AD病理时改善认知方面的作用。因此，恢复AHN已成为阿尔茨海默病治疗的一个有吸引力的目标。Bolden Therapeutics发现了一种促进AHN的新途径。关键的是，这一途径可以通过外显子跳跃反义寡核苷酸（ASOs）靶向，ASOs是一种市场上的治疗方式，并且在调节中枢神经系统的选择性剪接方面有效且安全。Valat博士领导了在培养细胞中成功跳过目标区域的几个先导ASOs的鉴定工作。在第一阶段的工作中，这些aso将在体内进行测试。我们将在衰老野生型小鼠（Aim 1）和AD病理根深蒂固的小鼠模型（Aim 2）中评估它们的安全性以及促进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关键的一步，将支持这些aso推进到ind实验和快速临床前开发。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，正如她在Bolden Therapeutics公司所做的识别主要aso的工作所证明的那样。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发挥主导作用-这对任何制药公司来说都是至关重要的一步。Valat博士的创业发展将由三位经验丰富的共同导师指导，他们将带来发现科学方面的技能和经验，与FDA互动，进行临床试验，照顾患者，创办公司，业务发展，筹款和投资新的科学发现。因此，这个奖项将使她成功地从基层工作过渡到企业家的位置。除了这种实践经验，Valat博士还将受益于LabCentral的一系列创业和职业发展计划，LabCentral是一家一流的生物技术孵化器，她目前正在进行Bolden的研究，NIH提供的项目，如I-Corps，以及麻省理工学院提供的密集创业发展计划。总的来说，该奖项将补充Valat博士的专业知识，并使她能够提高她作为研究科学家和生物技术行业未来领导者的技能。

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.