Short Stabilized EPO-Peptide as Therapeutic Agents for Multiple Sclerosis and Acute Brain Trauma

创伤性脑损伤和多发性硬化症是常见的人类神经系统疾病，其影响每个年龄组并具有长期后果，并且迫切需要为患者带来针对这些疾病的新的有效治疗剂。全长促红细胞生成素（EPO）驱动红细胞的形成（红细胞生成），已显示在中枢神经系统（CNS）疾病的各种临床前模型中具有有益作用，包括脱髓鞘疾病、急性脑创伤和中风。然而，由于过度红细胞生成的不良副作用，EPO作为CNS疾病的治疗方法的使用受到限制。罗格斯大学的合作者合成了短环EPO肽，以减少主要的造血副作用。先导化合物（JM 4）在TBI和MS的临床前动物模型中可高效阻断临床进展和炎症神经病理学。 BrIDG团队在完成以下关于JM 4的研究方面取得了进展： - 非GMP（良好生产规范）和GMP材料的合成 - 临床供应品的处方开发和生产 - 药代动力学/吸收、分布、代谢和排泄（PK/ADME）研究 - 研究性新药（IND）导向毒理学

Traumatic Brain Injury and Multiple Sclerosis are common human neurological disorders that affect every age group with longterm consequences, and there is a pressing medical need to bring new, effective therapeutic agents for these diseases to patients. Full-length erythropoietin (EPO), which drives formation of red blood cells (erythropoiesis), has been shown to have beneficial effects in various preclinical models of central nervous system (CNS) diseases, including demyelinating disease, acute brain trauma, and stroke. However, use of EPO as a treatment approach for CNS diseases is limited due to the undesirable side effects of excessive erythropoiesis. The collaborators at Rutgers have synthesized short cyclic EPO peptides in an effort to reduce the major hematopoietic side effects. The lead compound (JM4) is highly effective in blocking clinical progression and inflammatory neuropathology in preclinical animal models of TBI and MS. The BrIDGs team has made progress towards the completion of the following studies on JM4: - Synthesis of non-GMP (Good Manufacturing Practice) and GMP material - Formulation development and manufacture of clinical supplies - Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies - Investigational New Drug (IND)-directed toxicology