I-Corps: Restoration of Ovarian Endocrine Function in Adolescent Girls with Premature Ovarian Insufficiency

I-Corps：卵巢早衰女孩卵巢内分泌功能的恢复

• 批准号: 1910283
• 负责人: Ariella Shikanov
• 金额: $ 5万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1910283&HistoricalAwards=false
• 关键词: Corps; Restoration; Ovarian; Endocrine; Function

The broader impact/commercial potential of this I-Corps project is to identify stakeholders and customers and to develop the most appropriate path forward to translate the company's technology to the clinic and bring it to the patients. Currently young girls suffering from premature ovarian insufficiency (POI) as a result of anticancer treatments have limited and inadequate options to undergo puberty and start their transition into adult life. The existing hormone replacement therapy (HRT) applied to induce puberty in girls with POI leads to long-term morbidities, such as decreased bone density, predisposition to obesity and diabetes. The company's technology allows the restoration of ovarian endocrine function in prepubescent girls and has the potential to become a central mainstream treatment for POI, which would result in significant improvement of the short and long-term health and eliminate long-term morbidities associated with premature ovarian failure. The commercial benefit of the proposed treatment would result from significant lower health costs associated with obesity, diabetes and osteoporosis. This I-Corps project will further the company's understanding of the current state of the field and the value of the proposed technology, and help identify the next steps for preclinical and clinical studies. The company developed an immunoisolating capsule that supports the survival and function of ovarian allograft eliminating the need for immune suppression. The company's central hypothesis is that ovarian tissue secretes the gonadal hormones, estradiol, progesterone, androstenedione, activins and inhibins, in response to systemic hormone stimulation in a pulsatile and dynamic rate required for physiological progression through puberty, growth and associated metabolic changes. Experimental data from in vivo mouse and primate studies have demonstrated promising results of restoration of hormone function integrated in the endocrine system and neuroendocrine axis, with no evidence of immune rejection or local inflammatory adverse response. The next critical steps in the company's project is to perform customer discovery and identify partners for first-in-human trials.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个i-Corps项目的更广泛的影响/商业潜力是确定利益相关者和客户，并制定最合适的前进道路，将公司的技术转化为临床，并将其带给患者。目前，由于抗癌治疗而患有卵巢功能不全的年轻女孩在经历青春期并开始过渡到成年生活方面的选择有限和不足。现有的激素替代疗法(HRT)用于诱导POI女孩的青春期，会导致长期的疾病，如骨密度下降，易患肥胖症和糖尿病。该公司的技术可以恢复青春期前女孩的卵巢内分泌功能，并有可能成为POI的主要主流治疗方法，这将显著改善短期和长期健康，并消除与卵巢早衰相关的长期疾病。拟议治疗的商业利益将来自与肥胖、糖尿病和骨质疏松症相关的显著较低的医疗成本。这个i-Corps项目将进一步加深该公司对该领域的现状和拟议技术的价值的了解，并有助于确定临床前和临床研究的下一步步骤。该公司开发了一种免疫隔离胶囊，支持同种异体卵巢移植物的存活和功能，消除了免疫抑制的需要。该公司的核心假设是，卵巢组织分泌性激素、雌二醇、孕酮、雄烯二酮、激活素和抑制素，以脉动和动态的速度响应全身激素刺激，这是青春期、生长和相关代谢变化生理进程所需的。来自体内小鼠和灵长类动物的实验数据表明，内分泌系统和神经内分泌轴整合的激素功能恢复了令人振奋的结果，没有免疫排斥或局部炎症不良反应的证据。该公司项目的下一个关键步骤是进行客户发现并为首次人体试验确定合作伙伴。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。