Treatment of Dermatomyositis with Ajulemic Acid, a Non-Psychoactive Cannabinoid

描述（由申请人提供）：皮肌炎（DM）是一种严重的自身免疫性结缔组织疾病，患者通常需要长期接受全身治疗，这与其皮肤病的显著毒性相关。虽然在美国有超过60，000人患有DM，他们中的大多数人有皮肤发现，还没有对许多皮肤为主疾病患者的治疗进行前瞻性研究。该提案的目的是启动一项短期（12周治疗）临床研究，以检查阿佳酸对累及皮肤的难治性皮肌炎（DM）患者的作用。皮肌炎皮肤表现的患者生活质量极差，包括严重瘙痒和抑郁，目前的治疗往往无效。皮肤的第一线治疗是抗疟药，这通常是无效的或引起药物反应。我们提出了一个随机安慰剂对照的临床试验，在糖尿病患者难治性皮肤病，以测试的安全性和探索阿佳酸（AjA，一种合成的，非精神活性，抗炎，镇痛大麻素，与安慰剂相比，用于治疗与糖尿病相关的皮肤病的临床疗效。我们预计，从拟议的临床试验的结果将被用于功率更大的II期临床试验的AjA的临床疗效。为了测试AjA的生物学功效，将在给药前后检查IL-1β、IFNγ、IFNα、TNFα的血清水平和PBMC产生以及IFNα特征在PBMC中的表达。这些研究的成功完成也将使我们能够确定临床疗效的生物标志物终点，用于更大规模的临床试验。对于皮肌炎患者的皮肤病变的治疗，非常需要新的方法。这项临床研究将允许仔细观察一种潜在的令人兴奋的新治疗方法。

DESCRIPTION (provided by applicant): Dermatomyositis (DM) is a severe autoimmune connective tissue disease in which patients routinely endure prolonged courses of systemic treatments that are associated with significant toxicity for their skin disease. Although over 60,000 individuals have DM in the U.S., the majority of whom have skin findings, there have been no prospective studies of treatments for the many patients with skin predominant disease. The goal of this proposal is to initiate a short-term (12 week treatment) clinical study to examine the role of ajulemic acid for patients with refractory dermatomyositis (DM) involving the skin. Patients with skin manifestations of dermatomyositis have extremely poor quality of life, including severe pruritus and depression, and current therapies are frequently ineffective. First line treatment for the skin is antimalarials, which frequently are not effective or cause drug reactions. We propose a randomized placebo-controlled clinical trial in DM patients with refractory skin disease, to test the safety and explore the clinical efficacy of ajulemic acid (AjA, a synthetic, nonpsychoactive, anti-inflammatory, analgesic cannabinoid, compared to placebo for the treatment of skin disease associated with DM. We anticipate that results from the proposed clinical trial will be used to power a larger Phase II clinical trial for clinical efficac of AjA. To test biological efficacy of AjA, serum levels and PBMC production of IL-1β, IFNγ, IFNα, TNFα, and expression in PBMC of the IFNα signature will be examined before and after dosing. Successful completion of these studies should also allow us to determine biomarker endpoints for clinical efficacy to be used in a larger clinical trial. There is a great need for new approachs to treatment of the skin lesions of patients with dermatomyositis. This clinical study will allow careful observation of a potentially exciting new treatment.