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.

谓词STTR I期授予的项目摘要 围手术期和规定的阿片类药物通常会导致昂贵且不可预测的不利影响，包括生命 易受伤害的患者威胁呼吸道抑郁症和长期阿片类药物使用/滥用。美国FDA警告 由于术后缺氧脑损伤和死亡而反对儿童使用可待因和曲马多，并且 由于严重的呼吸问题和婴儿死亡，在护理母亲中。有一个紧急且未得到关键的 需要积极的风险识别和个性化的精确镇痛，以提高安全性和有效性 脆弱人群中的阿片类药物。主动的精确药物，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； CPIC指南；成本效益 并确定的基因分型保险可以最大程度地减少阿片类药物的使用和与之相关的危害 当前的反复试验，反应性医学。使用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I阶段ISTTR应用中，Opalgenix，Inc.。 提议验证护理母亲及其婴儿不良阿片类药物结局的遗传特征 剖宫产。 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）补充此STTR申请以追求以下两个目标： 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危险因素 经历剖宫产及其母乳喂养的新生儿，以及2）开发保险公司偿还多基因 实验室开发测试（LDT），用于儿科术前遗传风险预测和决策支持 成人手术患者，以防止阿片类药物不良预后。 Opalgenix将开发最低可行的产品 （MVP），一个由CLIA认证的实验室中的精制多基因面板，具有强大的组合药物遗传学 预测和决策支持，以确切的阿片类药物在儿童中个性化手术镇痛算法 和成人。这有望防止普通阿片类药物不良后果，例如呕吐和罕见生活 威胁和妥协结果，例如呼吸抑郁，慢性持续手术疼痛（CPSP）， 阿片类药物和成人手术队列中的阿片类药物依赖性以及阿片类药物使用障碍（OUD）。未来 II期STTR将重点介绍CLIA LDT的FDA预先批准，以鉴定患者遗传预先识别的患者 大量不良阿片类药物结局，包括过量，OUD和新生儿阿片类药物戒断联合体 （现在）。根据当前的阿片类药物流行，预计阿片类药物的2.15万亿美元经济负担 仅2020年和2040年就在美国，Opalgenix就存在一个重要的商业市场，可以主动识别和 有效地减少术后阿片类药物相关的不良反应，CPSP，OUD，NOWS和用药过量 每年数百万美国人的手术缓解最大化。

项目成果

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

• DOI: 10.1007/s12630-023-02536-w
• 发表时间: 2023-10
• 期刊: CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE
• 影响因子: 4.2
• 作者: Lilaonitkul, Maytinee;Cosden, Christopher W. W.;Markley, John C. C.;Pian-Smith, May;Lim, Grace;Yeh, Peter;Aleshi, Pedram;Boscardin, Christy;Sullivan, Kristina;George, Ronald B. B.
• 通讯作者: George, Ronald B. B.

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

• DOI: 10.3389/fgene.2023.1292148
• 发表时间: 2023
• 期刊: FRONTIERS IN GENETICS
• 影响因子: 3.7
• 作者: Radhakrishna, Uppala;Sadhasivam, Senthilkumar;Radhakrishnan, Rupa;Forray, Ariadna;Muvvala, Srinivas B.;Metpally, Raghu P.;Patel, Saumya;Rawal, Rakesh M.;Vishweswaraiah, Sangeetha;Bahado-Singh, Ray O.;Nath, Swapan K.
• 通讯作者: Nath, Swapan K.