XT-101: A Potent IL-10 Based Therapy for Treating Multiple Sclerosis.

描述（由申请人提供）：Xalud Therapeutics拟评估其新型强效抗炎疗法XT-101治疗运动性 在多发性硬化症（MS）的退行性和炎性自身免疫啮齿动物模型中的损伤、步态障碍和神经性疼痛。XT-101是一种非病毒形式的基因治疗，它能使脊髓周围的脑膜细胞分泌强大的、天然的、抗炎的白细胞介素-10（IL-10）。基于广泛的临床前研究，Xalud认为分泌的IL-10将减少炎症并使MS中观察到的病理性小胶质细胞和星形胶质细胞活性正常化。Xalud建议在MS的炎症和神经退行性啮齿动物模型中研究XT-101，并进行各种细胞和组织分析，以更好地理解和阐明XT-101的生物学作用。Xalud希望在这些模型中证明XT-101可以减少运动障碍，缓解步态障碍并解决神经性疼痛。Xalud还预计XT-101将对MS病理学的许多要素产生积极影响，包括：免疫细胞浸润、炎症、谷氨酸转运减少、脱髓鞘和神经元凋亡。支持拟议的研究将大大加快XT-101的临床应用开发。Xalud目前正在进行IND使能毒理学研究，以使用XT-101治疗神经性疼痛，预计将在2013年底提交IND。拟议研究提供的额外疗效数据将支持启动XT-101治疗神经性疼痛、步态障碍和可能的其他MS相关适应症的人体试验。Xalud认为，XT-101如果开发成功，将对MS的临床治疗产生巨大影响，并大大改善MS患者的生活质量。神经性疼痛和步态障碍影响几乎所有的MS患者，大大降低了他们参与社会和享受生活的能力。此外，XT-101可以减缓目前无法治疗的进展型MS的疾病进展。由于XT-101的作用方法与所有现有或即将到来的MS治疗方法明显不同，因此它有可能成为当前医疗实践的非常有用的补充和补充。

DESCRIPTION (provided by applicant): Xalud Therapeutics proposes to evaluate the applicability of its novel and potent anti-inflammatory therapy, XT-101, for the treatment of motor impairment, gait disorders, and neuropathic pain in degenerative and inflammatory autoimmune rodent models of multiple sclerosis (MS). XT-101 is a non-viral form of gene therapy that causes the meningeal cells surrounding the spinal cord to secrete the powerful, natural, anti- inflammatory interleukin-10 (IL-10). Based on extensive pre-clinical research, Xalud believes that the secreted IL-10 will reduce inflammation and normalize the pathological microglia and astrocyte activity that is seen in MS. Xalud proposes to study XT-101 in both inflammatory and neurodegenerative rodent models of MS and to conduct various cell and tissue analyses to better understand and elucidate the biological effects of XT-101. Xalud expects to demonstrate in these models that XT-101 reduces motor impairment, alleviates gait disorders and resolves neuropathic pain. Xalud also expects that XT-101 will have a positive effect on numerous elements of MS pathology including: immune cell infiltration, inflammation, reduced glutamate transport, demyelination, and neuronal apoptosis. Support of the proposed studies would greatly accelerate the development of XT-101 for clinical applications. Xalud is currently conducting IND-enabling toxicology studies for the use of XT-101 in neuropathic pain and expects to file an IND in late 2013. The additional efficacy data provided by the proposed studies would support the initiation of human trials of XT-101 in neuropathic pain, gait disorders and possibly other MS-related indications. Xalud believes that XT-101, if successfully developed, could have a tremendous impact on the clinical treatment of MS and greatly improve the quality of life MS patients. Neuropathic pain and gait disorders impact almost all MS patients and greatly reduce their ability to participate in society and enjoy life. Further, XT-101 may slow disease progression in the currently untreatable progressive forms of MS. Because the method of action of XT-101 is markedly different from all existing or imminent MS treatments, it has the potential to be an extremely useful addition and complement to current medical practice.