Oral IFN-tau treatment in RRMS patients

描述(申请人提供)：这个SBlR-AT第一阶段项目将评估重组绵羊干扰素tau(RolFN-tau)治疗多发性硬化症(MS)患者的安全性、作用机制和临床效果。干扰素-tau是一种1型干扰素，具有生物活性，包括抗炎作用，类似于其他1型干扰素、LFN-α和干扰素-β。然而，与干扰素-α和干扰素-β相反，LFN-tau具有口服生物活性。口服时，干扰素-tau在啮齿动物和人类体内诱导IL-10，降低LFN-Gamma，并防止多发性硬化症的动物模型-实验性过敏性脑脊髓炎(EAE)的症状和体征。此外，根据I期临床试验的结果，LFN-tau似乎具有极好的耐受性，并且比注射LFN-α或干扰素-β产生的副作用更少。在这项拟议的项目中，将在为期9个月的临床试验中，对20名复发-缓解型多发性硬化症患者每日口服单一剂量的rofn-tau的效果进行评估。将仔细监测安全性和耐受性，而干扰素-tau对T细胞介导的免疫的影响将通过检测治疗前、治疗中和治疗后血清和全血中Th1和Th2细胞因子的水平来确定。疾病进展的评估将基于MRI每月连续测定Gd增强斑块的数量。这项试验的结果将使我们能够确定LFN-tau治疗多发性硬化症的安全性和治疗潜力，并为设计更大、更长时间的临床对照试验提供基础。

DESCRIPTION (provided by applicant): This SBlR-AT Phase I project will evaluate the safety, mechanism of action, and clinical effects of recombinant ovine Interferon tau (rolFN-tau) in patients with multiple sclerosis (MS). IFN-tau is a Type 1 interferon that possesses biological activity, including anti-inflammatory effects, similar to that of other Type 1interferons, lFN-alpha and IFN-beta. However, in contrast to IFN-alpha and IFN-beta, lFN-tau is orally bioactive. When administered orally, IFN-tau induces IL-10 and reduces lFN-gamma in rodents and humans, and prevents the symptoms and signs of experimental allergic encephalomyelitis (EAE), an animal model of MS. Moreover, based on the results of Phase I clinical trials, lFN-tau appears to be extremely well tolerated and causes fewer side effects than injected lFN-alpha or IFN-beta. In the proposed project, the effects of a single daily oral dose of rolFN-tau will be evaluated in twenty patients with relapsing-remitting MS in a nine-month clinical trial. Safety and tolerability will be carefully monitored, while the effects of IFN-tau on T cell-mediated immunity will be determined by measuring the levels of Th1 and Th2 cytokines in serum and in white blood ceils (WBC) from whole blood from before, during, and after treatment. Assessment of disease progression will be based on serial monthly determinations of the number of gadolinium-enhanced plaques by MRI. The results of this trial should allow us to determine the safety and therapeutic potential of lFN-tau in MS and provide the basis for designing a larger, longer controlled clinical trial