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，患者通常要忍受长时间的全身治疗，这与皮肤疾病的显著毒性有关。尽管在美国有超过60,000人患有糖尿病，其中大多数人有皮肤症状，但对于许多皮肤显性疾病患者的治疗方法尚无前瞻性研究。本提案的目标是启动一项短期（12周治疗）临床研究，以检查阿菊酸对难治性皮肌炎（DM）患者的作用。皮肤表现为皮肌炎的患者生活质量极差，包括严重的瘙痒和抑郁，目前的治疗往往无效。对皮肤的一线治疗是抗疟药，但往往无效或引起药物反应。我们建议在患有难治性皮肤病的糖尿病患者中进行一项随机安慰剂对照临床试验，以测试阿菊酸（AjA）（一种合成的、无精神活性、抗炎、镇痛的大麻素）与安慰剂相比治疗糖尿病相关皮肤病的安全性和临床疗效。我们预计，拟议临床试验的结果将用于推动更大规模的II期临床试验，以验证AjA的临床疗效。为了检测AjA的生物学功效，我们将在给药前后检测AjA的血清水平和PBMC中IL-1β、IFNγ、IFNα、TNFα的产生，以及PBMC中IFNα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。有一个很大的需要新的方法来治疗皮肌炎患者的皮肤病变。这项临床研究将允许仔细观察一种潜在的令人兴奋的新疗法。

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.