Oral IFN-tau treatment in RRMS patients

描述（由申请人提供）：本SBlR-AT I期项目将评价重组绵羊干扰素tau（rolFN-tau）在多发性硬化（MS）患者中的安全性、作用机制和临床效果。IFN-tau是一种1型干扰素，具有与其他1型干扰素IFN-alpha和IFN-β相似的生物活性，包括抗炎作用。然而，与IFN-α和IFN-β相反，IFN-tau是口服生物活性的。当口服给药时，IFN-tau在啮齿动物和人类中诱导IL-10并减少IFN-γ，并预防实验性过敏性脑脊髓炎（EAE）（MS的动物模型）的症状和体征。此外，基于I期临床试验的结果，IFN-tau似乎耐受性非常好，并且比注射的IFN-a或IFN-β引起更少的副作用。在拟议的项目中，将在为期9个月的临床试验中评估20名复发缓解型MS患者每日单次口服rolFN-tau的效果。将仔细监测安全性和耐受性，而IFN-τ对T细胞介导的免疫的影响将通过测量治疗之前、期间和之后的血清和来自全血的白色血细胞（WBC）中的Th 1和Th 2细胞因子的水平来确定。疾病进展的评估将基于通过MRI对钆增强斑块数量的连续每月测定。这项试验的结果将使我们能够确定IFN-tau在MS中的安全性和治疗潜力，并为设计更大，更长的对照临床试验提供基础。

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