THERAPY FOR ALCOHOL USE DISORDER

酒精使用障碍的治疗

基本信息

批准号：
10820349
负责人：
HERBERT H SELTZMAN
金额：
$ 36.87万
依托单位：
ARTIAM BIO INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-25 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10820349
关键词：
Acute Adverse effects Affect Affinity Age Agonist Alcohol consumption Alcoholism American Anhedonia Anxiety BALB/cByJ Mouse Behavior Behavioral Behavioral Assay Binding Biological Assay Biotechnology CNR1 gene Cannabinoids Chronic Clinical Clinical Trials Coupled Darkness Data Development Disease Dissociation Dose Drug Metabolic Detoxication Eligibility Determination Emotional Endocannabinoids Enzymes Event Feeling suicidal Funding Future Generations Goals Human In Vitro Inbred Strain Investments Knowledge Lead Licensing Ligands Light Lipids Mediating Mental Depression Modeling Mus Naltrexone North Carolina Patients Personal Satisfaction Persons Pharmaceutical Preparations Pharmacotherapy Phase Placebo Effect Privatization Process Property Purines Rattus Regimen Relapse Research Personnel Rewards Risk Rodent Role Route SR 141716A Self Administration Self Stimulation Signal Induction Signal Transduction Small Business Innovation Research Grant Small Business Technology Transfer Research Testing Therapeutic Toxicology Universities addiction alcohol relapse alcohol research alcohol use disorder antagonist anxiety-like behavior behavioral study cannabinoid receptor clinical development conditioned fear design drug development efficacy study endogenous cannabinoid system experience global health hedonic in vivo innovation lead candidate meetings nanomolar neuropsychiatry new technology novel novel therapeutics patient subsets pharmacologic pre-clinical preclinical study preference preservation primary endpoint receptor rimonabant success trend welfare

项目摘要

Abstract Alcohol use disorder (AUD) is a major global health issue. In the US, AUD affects over 14 million people over the age of 18. While there are three approved drugs for AUD, less than 4% of patients eligible for pharmacotherapy are prescribed a medication – likely due to limited efficacy of currently approved agents. Also, the relapse rate for AUD continues to be exceedingly high. Thus, new therapies are urgently needed for AUD. Both preclinical and clinical evidence suggest that antagonism of the type 1 cannabinoid (CB1) receptor is a promising strategy for AUD. However, first generation CB1 blockers produced adverse psychiatric effects in ~6% of patients making them unsuitable for chronic use. Artiam Bio is developing second generation CB1 blockers that are designed to be efficacious without producing adverse psychiatric effects. Artiam Bio’s approach takes into consideration that intrinsic activity of the CB1 receptor is required for emotional welfare, and that first-generation full inverse agonists/antagonists like SR141716A (rimonabant) completely abrogated this necessary beneficial process. The compounds developed by Artiam, including its lead molecule and backup, are high affinity but low intrinsic efficacy partial inverse agonists that preserve basal activity of the CB1 receptor – thereby reducing the potential of adverse neuropsychiatric events. Supportive evidence comes from rodent studies presented in this application. For this Phase 1 STTR application, Artiam’s team will partner with investigators from University of North Carolina’s Bowles Alcohol Research Center to perform efficacy studies with its lead compound in a rat model of alcohol consumption and relapse. Further, additional behavioral studies are proposed in anxiety-prone mice using a chronic dosing regimen to further de-risk Artiam’s lead compound for clinical development. Successful completion of these studies will pose Artiam’s lead compound, which has good drug-like properties, for clinical development to treat AUD.

抽象的酒精使用障碍（AUD）是一个主要的全球健康问题。在美国，AUD影响超过1400万人 18岁。虽然有三种批准的AUD药物，但不到4％的患者有资格进行药物治疗处方药物 - 可能是由于当前批准的代理商的效率有限。此外，继电器率对于AUD仍然很高。这是迫切需要AUD的新疗法。都是临床前临床证据表明，1型大麻素（CB1）受体的拮抗作用是一种有前途的策略对于aud。但是，第一代CB1阻滞剂在约6％的患者中产生了不良的精神病作用它们不适合长期使用。 Artiam Bio正在开发旨在的第二代CB1阻滞剂在不产生不良精神效果的情况下要高效。 Artiam Bio的方法考虑到情绪福利需要CB1受体的固有活性，而第一代完全逆像SR141716A（Rimonabant）这样的激动剂/拮抗剂完全废除了这一必要的有益过程。这由Artiam开发的化合物，包括其铅分子和备份，是高亲和力，但内在较低效率局部反向激动剂，保留CB1受体的基本活性 - 从而降低了不良神经精神事件的潜力。支持证据来自于此提出的啮齿动物研究应用。对于此第1阶段的STTR应用程序，Artiam的团队将与大学的调查员合作北卡罗来纳州的鲍尔斯酒精研究中心，以其铅化合物在老鼠中进行效率研究饮酒和救济模型。此外，在容易发生焦虑中提出了其他行为研究使用长期给药方案的小鼠为临床发育进一步脱离危险的铅化合物。这些研究的成功完成将构成Artiam的铅化合物，该化合物具有良好的药物样特性，用于临床开发以治疗AUD。