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

描述(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，患者通常需要忍受长期的全身治疗，这与他们的皮肤病的显著毒性有关。尽管美国有超过6万人患有糖尿病，其中大多数人有皮肤症状，但还没有针对许多以皮肤病为主的患者的前瞻性研究。这项建议的目标是启动一项短期(12周治疗)临床研究，以检查阿魏酸对累及皮肤的难治性皮肌炎(DM)患者的作用。有皮肤症状的皮肌炎患者的生活质量极差，包括严重的瘙痒和抑郁，目前的治疗方法往往无效。皮肤的一线治疗是抗疟疾药物，这些药物往往无效或引起药物反应。我们提出了一项针对糖尿病难治性皮肤病患者的随机安慰剂对照临床试验，以测试AJA的安全性，并探索与安慰剂相比，AJA(一种合成的非精神活性、抗炎、止痛的大麻素)治疗与DM相关的皮肤病的临床疗效。我们预计，拟议临床试验的结果将被用于为AJA临床疗效的更大的II期临床试验提供动力。给药前后检测血清IL-1β、干扰素γ、干扰素α、肿瘤坏死因子α的水平及细胞表面干扰素α的表达，以验证AJA的生物学效应。这些研究的成功完成还将使我们能够确定临床疗效的生物标记物终点，并用于更大的临床试验。治疗皮肌炎患者的皮损非常需要新的治疗方法。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.