Avoiding Adverse Opioid Outcomes with Proactive Precision Care

通过积极的精准护理避免阿片类药物的不良后果

• 批准号: 10541694
• 负责人: Steven R. Plump
• 金额: $ 5.5万
• 依托单位: OPALGENIX, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10541694
• 关键词: Absence of pain sensation; Adult; Adverse effects; Algorithms; American; Analgesics; Anoxic Encephalopathy; Brain Death; Breast Feeding; Breathing; CLIA certified; Cesarean section; Cessation of life; Child; Childhood; Chronic; Clinical; Codeine; Complement; Dose; Economic Burden; Effectiveness; Funding; Future; Genetic Predisposition to Disease; Genetic Risk; Genotype; Grant; Guidelines; Insurance Carriers; Insurance Coverage; Laboratories; Legal patent; Life; Medicine; Neonatal; Operative Surgical Procedures; Opiate Addiction; Opioid; Outcome; Overdose; Patients; Perioperative; Pharmacogenetics; Phase; Postoperative Period; Research Personnel; Risk; Safety; Small Business Technology Transfer Research; Testing; Tramadol; United States National Institutes of Health; Ventilatory Depression; Vomiting; Vulnerable Populations; Woman; adverse outcome; base; cohort; combinatorial; commercially viable technology; cost; cost effective; cost effectiveness; gene panel; genetic risk factor; genetic signature; improved; infant death; innovation; neonate; nursing mothers; opioid epidemic; opioid use; opioid use disorder; opioid withdrawal; pain relief; personalized care; postcesarean section; precision medicine; prescription opioid; prevent; public health relevance; risk prediction; surgical pain

PROJECT SUMMARY FOR PREDICATE STTR PHASE I GRANT Perioperative and prescribed opioids often result in costly and unpredictable adverse effects, including life threatening respiratory depression and long-term opioid use/misuse in vulnerable patients. The US FDA warns against the use of codeine and tramadol in children due to postoperative anoxic brain injuries and deaths, and in nursing mothers due to serious breathing problems and infantile death. There is an urgent and unmet critical need for proactive risk identification and personalized precision analgesia to improve safety and effectiveness of opioids in vulnerable populations. Proactive precision medicine, including preoperative genotyping and personalized analgesia based on scientific evidence; regulatory warnings; CPIC guidelines; cost-effectiveness and established insurance coverage for genotyping could minimize excess opioid use and harm associated with the current trial and error, reactive medicine. Using a patent protected innovative multigene combinatorial pharmacogenetic opioid risk prediction and decision algorithm, in this Phase I STTR application, OpalGenix, Inc. proposes to validate the genetic signatures of adverse opioid outcomes in nursing mothers and their babies after cesarean deliveries. OpalGenix team will partner with academic researchers and leverage nonoverlapping NIH R01 funding (HD089458 and HD096800) to complement this STTR application to pursue the following two aims: 1) Validate and identify genetic risk factors associated with postoperative opioid adverse effects in adult women undergoing cesarean section and their breastfed neonates, and 2) Develop an insurer reimbursed multi-gene laboratory-developed test (LDT) for preoperative genetic risk prediction and decision support for pediatric and adult surgical patients to prevent adverse opioid outcomes. OpalGenix will develop a minimum viable product (MVP), a refined multi-gene panel in a CLIA certified laboratory with a robust combinatorial pharmacogenetic prediction and decision support to personalize surgical analgesia algorithm with precise opioid use in children and adults. This is expected to prevent common opioid adverse outcomes, such as vomiting and rare life threatening and compromising outcomes like respiratory depression, chronic persistent surgical pain (CPSP), opioid dependence, and opioid use disorder (OUD) in vulnerable pediatric and adult surgical cohorts. A future Phase II STTR will focus on the FDA pre-approval for a CLIA LDT to identify patients genetically pre-disposed to significant adverse opioid outcomes including overdose, OUD, and Neonatal Opioid Withdrawal Syndome (NOWS). Based on the current opioid epidemic and projected $2.15 trillion economic burden of opioids between 2020 and 2040 in the US alone, a significant commercial market exists for OpalGenix to proactively identify and effectively reduce postoperative opioid-related adverse effects, CPSP, OUD, NOWS, and overdose while maximizing surgical pain relief in millions of Americans each year.

PREDICATE STTR 第一阶段拨款项目摘要 围手术期和处方阿片类药物通常会导致代价高昂且不可预测的不良影响，包括生命 威胁呼吸抑制和弱势患者长期使用/滥用阿片类药物。美国FDA警告 反对因术后缺氧性脑损伤和死亡而在儿童中使用可待因和曲马多，以及 哺乳期母亲因严重呼吸问题和婴儿死亡。有一个紧急且未满足的关键问题 需要主动风险识别和个性化精准镇痛，以提高安全性和有效性 弱势人群中的阿片类药物。主动精准医学，包括术前基因分型和 基于科学证据的个性化镇痛；监管警告；太保指引；成本效益 建立基因分型保险范围可以最大限度地减少阿片类药物的过量使用和与阿片类药物相关的伤害 当前的试错，反应医学。使用受专利保护的创新多基因组合 药物遗传学阿片类药物风险预测和决策算法，在此 I 期 STTR 应用中，OpalGenix, Inc. 提议验证哺乳母亲及其婴儿在使用阿片类药物后不良后果的遗传特征 剖腹产。 OpalGenix 团队将与学术研究人员合作并利用非重叠的 NIH R01 资金（HD089458 和 HD096800）是对 STTR 申请的补充，以实现以下两个目标： 1) 验证并确定与成年女性术后阿片类药物不良反应相关的遗传风险因素 接受剖腹产手术及其母乳喂养的新生儿，以及 2) 开发保险公司报销的多基因 实验室开发的测试（LDT），用于儿科和儿童的术前遗传风险预测和决策支持 成人手术患者预防阿片类药物不良后果。 OpalGenix 将开发最小可行产品 (MVP)，在 CLIA 认证的实验室中精制的多基因面板，具有强大的组合药物遗传学 预测和决策支持，通过精确的儿童阿片类药物使用来个性化手术镇痛算法 和成人。这有望预防常见的阿片类药物不良后果，例如呕吐和罕见的生命 威胁和损害结果，如呼吸抑制、慢性持续性手术疼痛 (CPSP)、 弱势儿科和成人手术人群中的阿片类药物依赖和阿片类药物使用障碍（OUD）。未来 II 期 STTR 将重点关注 FDA 对 CLIA LDT 的预先批准，以识别具有遗传倾向的患者 严重的阿片类药物不良后果，包括过量、OUD 和新生儿阿片类药物戒断综合征 （现在）。根据当前阿片类药物流行情况以及预计 2017 年阿片类药物造成的 2.15 万亿美元经济负担 2020 年和 2040 年，仅在美国，OpalGenix 就存在一个重要的商业市场，需要主动识别和 有效减少术后阿片类药物相关不良反应、CPSP、OUD、NOWS 和过量使用 每年最大限度地缓解数百万美国人的手术疼痛。

项目成果

Development of obstetric anesthesia core competencies for USA residency programs through a Delphi process.

通过德尔菲流程开发美国住院医师计划的产科麻醉核心能力。

• 发表时间: 2023-10
• 作者: Lilaonitkul, Maytinee;Cosden, Christopher W;Markley, John C;Pian;Lim, Grace;Yeh, Peter;Aleshi, Pedram;Boscardin, Christy;Sullivan, Kristina;George, Ronald B
• 通讯作者: George, Ronald B

Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons.

暴露于产前阿片类药物的婴儿的胎盘细胞色素 P450 甲基化：探索新生儿阿片类药物戒断综合征对健康视野的影响。

• 发表时间: 2023
• 作者: Radhakrishna, Uppala;Sadhasivam, Senthilkumar;Radhakrishnan, Rupa;Forray, Ariadna;Muvvala, Srinivas B;Metpally, Raghu P;Patel, Saumya;Rawal, Rakesh M;Vishweswaraiah, Sangeetha;Bahado;Nath, Swapan K
• 通讯作者: Nath, Swapan K