Novel ex-vivo Immunoadsorption Therapy to Treat Preeclampsia

治疗先兆子痫的新型离体免疫吸附疗法

基本信息

批准号：
8592517
负责人：
Woo Joo
金额：
$ 24.51万
依托单位：
AGGAMIN PHARMACEUTICALS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8592517
关键词：
Adsorption Affect Angiogenesis Inhibitors Animals Antibodies Anticonvulsants Antihypertensive Agents Biotechnology Blood Blood Component Removal Blood Proteins Cerebral hemisphere hemorrhage Cessation of life Clinical Communities Cyclic GMP Devices Diabetes Mellitus Dialysis procedure Disease Eclampsia Edema Effectiveness Endoglin Fetus Future Goals HELLP Syndrome Health Healthcare Systems Human Hypertension Incidence Innovative Therapy Intervention Ischemia Lead Life Magnesium Sulfate Marketing Maternal Age Modeling Monoclonal Antibodies Morbidity - disease rate Mothers Multiple Birth Offspring Nature Newborn Infant Obesity Organ failure Outcome Papio Patients Phase Physiology Placenta Placental Growth Factor Plasma Pre-Eclampsia Pregnancy Pregnancy Rate Pregnant Women Premature Birth Prolonged Pregnancy Proteinuria Recombinants Relative (related person)Risk Risk Factors Safety Seizures Small Business Innovation Research Grant Staging Symptoms System Therapeutic Time Vascular Diseases Vascular Endothelial Growth Factor Receptor Woman Work commercial application commercialization cost early onset effective therapy fetal high risk improved medically underserved mortality neonate novel patient population patient safety pregnancy disorder prototype public health relevance stable cell line standard of care

项目摘要

DESCRIPTION (provided by applicant): Preeclampsia (PE) is a pregnancy-induced hypertensive disorder without an effective treatment. The goal of this project is to produce a novel and safe therapy for PE. PE is the leading cause of pregnancy-related morbidity and mortality in the US, affecting over 200,000 pregnant women and newborns annually, at a significant cost to the healthcare system. PE is characterized by the onset of hypertension and proteinuria and can lead to more serious complications, such as seizure (eclampsia) and HELLP syndrome associated with systemic organ failure and death. Current interventions to treat PE include magnesium sulfate as an anticonvulsant and antihypertensive drugs, which can sometimes manage symptoms but do not target the underlying causes of the disease. Antiangiogenic factors, soluble VEGF Receptor 1 (sVEGFR1) and soluble Endoglin (sEng), are elevated in PE patients and are associated with adverse clinical outcomes. Aggamin proposes to develop a novel immunoadsorption therapy to remove excess levels of antiangiogenic factors sVEGFR1 and sEng from PE patients. Due to the nature of the high-risk patient population and safety requirements, this therapy is an extracorporeal treatment similar to dialysis. The long term goal is to develop and commercialize a therapeutic device for PE to improve health outcomes by reducing maternal symptoms and extending fetal gestation to 36 weeks. For Phase I, we hypothesize that a scaled-down cartridge packed with aVEGFR1 and aEng antibodies can remove sVEGFR1 and sEng protein from blood, using conditions that mimic clinical apheresis treatment. In Phase II, Aggamin will initiate cGMP manufacturing, produce a prototype device and conduct studies in a baboon PE model for efficacy and safety. PE affects 3-8% of all pregnancies and disease incidence is rising as risk factors such as obesity, diabetes, women's age at pregnancy and the rate of multiple births increase. The market for Aggamin's treatment for severe PE cases, evident before 34 weeks, is estimated at up to 25,000 patients in the US, and could later increase to include PE cases where symptoms appear after 34 weeks. Reimbursement rates for adsorption apheresis range from $5-10,000 and could be justified for PE patients by reducing or eliminating ICU costs and improved health outcomes for the newborn and mother. The total market for Aggamin's therapeutic product to treat severe early-onset PE cases in the US is estimated at $0.5-1.5 billion.

描述（由申请人提供）：先兆子痫（PE）是一种妊娠引起的高血压疾病，目前尚无有效治疗方法。该项目的目标是开发一种新颖且安全的 PE 疗法。 PE 是美国妊娠相关发病率和死亡率的主要原因，每年影响超过 200,000 名孕妇和新生儿，给医疗保健系统带来巨大成本。 PE 的特点是高血压和蛋白尿，可导致更严重的并发症，例如癫痫发作（子痫）和与全身器官衰竭和死亡相关的 HELLP 综合征。目前治疗肺栓塞的干预措施包括使用硫酸镁作为抗惊厥药和抗高血压药，这些药物有时可以控制症状，但不能针对疾病的根本原因。抗血管生成因子、可溶性 VEGF 受体 1 (sVEGFR1) 和可溶性内皮糖蛋白 (sEng) 在 PE 患者中升高，并与不良临床结果相关。 Aggamin 提议开发一种新型免疫吸附疗法，以去除 PE 患者体内过量的抗血管生成因子 sVEGFR1 和 sEng。由于高危患者群体的性质和安全要求，该疗法是一种类似于透析的体外治疗。长期目标是开发一种早泄治疗装置并将其商业化，通过减少孕产妇症状并将胎儿妊娠延长至 36 周来改善健康结果。对于第一阶段，我们假设装有 aVEGFR1 和 aEng 抗体的按比例缩小的药筒可以使用模拟临床单采治疗的条件从血液中去除 sVEGFR1 和 sEng 蛋白。在第二阶段，Aggamin 将启动 cGMP 制造，生产原型设备并在狒狒 PE 模型中进行功效和安全性研究。 PE 影响 3-8% 的妊娠，并且随着肥胖、糖尿病、女性妊娠年龄和多胞胎率等危险因素的增加，该病的发病率正在上升。 Aggamin 治疗 34 周前出现的严重肺栓塞病例的市场估计在美国有多达 25,000 名患者，并且随后可能会扩大到包括 34 周后出现症状的肺栓塞病例。吸附分离术的报销范围为 5-10,000 美元，通过减少或消除 ICU 费用以及改善新生儿和母亲的健康结果，对于 PE 患者来说是合理的。在美国，Aggamin 治疗严重早发性肺栓塞病例的治疗产品的总市场估计为 0.5-15 亿美元。