美国在研的“多发性硬化”基金高达118项！大数据分析，并附两项经典课题设计（2024）
Bringing medical advances from the lab to the clinic.
多发性硬化（Multiple Sclerosis，简称MS）是一种慢性疾病，主要影响中枢神经系统，包括大脑、脊髓和视神经。这种病症被归类为自身免疫性疾病，因为它涉及到免疫系统错误地攻击和破坏健康的神经细胞的保护层--髓鞘。MS可能表现为发作性疾病，患者在发作期间症状会突然恶化，之后可能部分或完全缓解。而在某些患者中，MS可能表现为持续进行性，意味着病情会逐渐恶化，没有明显的缓解期。
尽管近年来在多发性硬化的诊断和治疗方面取得了显著进展，但仍存在一些重要而未解决的临床问题：
疾病预测和早期诊断：尽管已经有一些诊断工具和生物标记物，但MS的早期诊断仍然具有挑战性，因为早期症状往往非特异性且可变。 个体化治疗：目前虽有多种疗法可减轻症状和延缓疾病进展，但因为患者间的表现形式和病程差异很大，如何为每位患者定制最合适的治疗方案仍然是一个问题。 无法根治：目前还没有治愈多发性硬化的方法。现有治疗主要集中在控制症状和延缓疾病进程。 长期管理的复杂性：随着患者年龄增长和疾病持续时间延长，如何有效管理长期并发症和生活质量下降成为一大挑战。
解决这些问题需要进一步的研究来理解MS的病理机制，开发新的生物标记物和治疗策略。此外，跨学科方法在患者的长期护理和生活质量管理中也显得尤为重要。
NEUROLOGICAL DISORDERS AND STROKE 的 REICH, DANIEL
JOHNS HOPKINS UNIVERSITY 的 CALABRESI, PETER A CLEVELAND CLINIC LERNER COM-CWRU 的 ONTANEDA, DANIEL WEILL MEDICAL COLL OF CORNELL UNIV 的 GAUTHIER, SUSAN A UNIVERSITY OF CALIFORNIA, SAN FRANCISCO 的 HAUSER, STEPHEN L
国立神经疾病与卒中研究所（NINDS） 加州大学旧金山分校
约翰霍普金斯大学
克利夫兰诊所
西奈山伊坎医学院等
The CentrAl Vein Sign in MS (CAVS-MS) study seeks to answer whether the central vein sign (CVS) can be used as a sensitive and specific diagnostic marker for a diagnosis of MS. The study will investigate the CVS in a mixed population of participants with typical and atypical clinical presentations including radiological presentations without neurological symptoms. The study will enroll 200 patients with typical clinical presentations and 200 participants with atypical presentations (total 400) who present to an MS center for a diagnostic referral and will follow study participants for up to 24 months to determine the specificity and sensitivity of the central vein sign for a diagnosis of MS using McDonald 2017 at 2 years as the gold standard for diagnosis.
The overarching goal of this multi-center proposal is to allow incorporation of the CVS — an easy-to-measure radiological biomarker — into the diagnostic criteria for MS, thereby facilitating earlier and more accurate diagnosis. Defining CVS criteria and patterns in typical and atypical MS presentations, as well as determining accuracy and speed of diagnosis, will inform public health interventions in MS.
Our goal is to develop a novel, immunological-directed synthetic biology-based therapeutic for the treatment of Multiple Sclerosis (MS).
A promising approach for the treatment of MS is to leverage the body’s own natural microbiome- associated immune regulatory mechanisms with oral, gut localized and targeted therapy to control host immune cells lining the gut epithelial layer to direct reestablishment of systemic immune homeostasis. R-2487 is an immunologically-directed recombinant probiotic consisting of the food-grade, Lactococcus (L.) lactis strain expressing Colonization Factor Antigen I (CFA/I). R-2487 is a live biotherapeutic product that represents a novel breakthrough approach for the treatment of MS by combining the safety of a probiotic with the targeted functionality of the CFA/I ligand. R-2487 has been showed to diminish MS-like symptoms in animals. R-2487 works via targeted delivery of CFA/I to the intestinal tract where it engages mucosal dendritic cells to drive systemic upregulation of Tregs. The induction of Tregs resets the balance with proinflammatory T effector cells to reduce inflammatory processes that contribute to autoimmune disease, leading to bystander tolerance. Since heterogeneous pathogenesis of autoimmune disease, including MS, poses many challenges for therapies that target specific antigens for tolerization or a single cell type or cytokine, R-2487-mediated bystander tolerance induction offers a broader and more impactful mechanism of disease correction.
This application is designed to complete R-2487 IND enabling studies to support initiation of a first-in-human MS trial for this important new therapy. The key aims of this proposal are: 1) finalize in vivo characterization of R-2487, identifying starting clinical dose and important biomarkers to be used in the clinical trial; 2) manufacture of clinical GMP drug substance and drug product; and 3) complete the IND-enabling GLP toxicology study. Successful commercialization of R-2487 will provide a profound medical advancement for treating MS.