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人类常见的神经系统疾病，影响每个年龄段，并具有长期后果，医学上迫切需要为这些疾病带来新的、有效的治疗药物。全长促红细胞生成素(EPO)可以促进红细胞的形成，在中枢神经系统(CNS)疾病的各种临床前模型中具有良好的效果，包括脱髓鞘疾病、急性脑创伤和中风。然而，EPO作为一种治疗中枢神经系统疾病的方法，由于过度红细胞生成的不良副作用而受到限制。罗格斯大学的合作者已经合成了短的环状EPO多肽，以努力减少主要的造血副作用。先导化合物(JM4)对临床前脑损伤和MS动物模型的临床进展和炎性神经病理具有高效的阻断作用。 Bridgs团队在完成关于JM4的以下研究方面取得了进展： -非GMP(良好制造规范)和GMP材料的合成 -临床用品的配方开发和制造 -药代动力学/吸收、分布、代谢和排泄(PK/ADME)研究 -研究新药(IND)指导的毒理学

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