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A First-in-Class Human Antibody Therapeutic for Treatment of Cushing's Disease

用于治疗库欣病的一流人类抗体疗法

基本信息

批准号：
9909906
负责人：
James Zanghi
金额：
$ 22.46万
依托单位：
ELIXERA, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-19 至 2020-09-17
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9909906
关键词：
Abdomen Address Adrenal Cortex Adrenal Gland Hyperfunction Adrenal Glands Adrenalectomy Affect Affinity Animal Model Animals Antibodies Antibody Formation Antigens Anxiety Bilateral Binding Biological Biological Assay Blood Carrier Proteins Cell Line Chest Circadian Rhythms Corticotropin Corticotropin Receptors Cushing Syndrome Desire for food Development Endocrine System Diseases Epitopes Exocrine pancreas Face Flushing Frequencies Glucocorticoid Receptor Glucocorticoids Goals Grant Growth Hair Human Hybridomas Hydrocortisone Hypertension Immune response Immunization Immunoglobulins In Vitro Individual Intervention Irregular Menstruation Left Leg Length Libraries Life Literature Lymphoid Tissue Medical Medicine Mental Depression Metabolism Mission Modeling Moods Mouse Strains Muscle Weakness Neuropeptides Operative Surgical Procedures Osteoporosis Parents Patient Care Patients Peptides Pharmaceutical Preparations Pharmacotherapy Phase Physiological Pituitary Diseases Pituitary Gland Pituitary Neoplasms Pituitary-dependent Cushing&apos s disease Plant Roots Pro-Opiomelanocortin Process Production Property Protocols documentation Rat Strains Recombinants Rest Role Serum Skin Skin Pigmentation Small Business Innovation Research Grant Solvents Specificity Steroid biosynthesis Steroids Stress Structure Testing Therapeutic Monoclonal Antibodies Therapeutic antibodies Thirst Time Toxicity Tests Transgenic Mice United States National Institutes of Health Urination Validation Weight Gain Woman Work alpha-Melanocyte stimulating hormone arm cabergoline cell type cross reactivity design disorder control drug candidate energy balance experience in vivo inhibitor/antagonist innovation lead candidate lead optimization manufacturability melanocortin receptor men novel novel strategies patient population polyclonal antibody polyclonal human antibody polypeptide pre-clinical preclinical efficacy protein aminoacid sequence receptor screening side effect somatostatin analog steroid hormone tumor

项目摘要

Cortisol is a steroid hormone that regulates a wide range of processes throughout the body, including metabolism and the immune response. It also has a very important role in helping the body respond to stress. High levels of adrenocorticotropic hormone (ACTH) in the adrenal glands stimulate the secretion of cortisol, causing blood levels of cortisol to rise. Too much cortisol for a long period of time leads to a condition called Cushing’s syndrome, characterized by rapid weight gain mainly in the face, chest and abdomen contrasted with slender arms and leg, a flushed and round face, high blood pressure, osteoporosis, skin changes, muscle weakness, mood swings that show as anxiety, depression or irritability and increased thirst and frequency of urination. When Cushing’s syndrome is caused by a tumor of the pituitary gland that secretes too much ACTH, the condition is known as Cushing’s disease. For reasons that are unclear, Cushing’s disease affects women more often than men by almost 3 to 1. Women with Cushing’s disease may experience irregular menstruation and have excessive hair growth on their face, abdomen, and legs. Left untreated, Cushing’s disease can be deadly, and the preferred course of action is to surgically remove the tumor without damaging the rest of the pituitary gland. When surgery is not possible or fails to completely remove the tumor, medication is often needed to block the effects of the excess cortisol. While steroid synthesis inhibitors, glucocorticoid receptor blockers, cabergoline, and somatostatin analogs have certainly made a great difference in the care of patients with Cushing’s disease, a substantial number of these patients are never adequately treated. There is a clear unmet medical need for novel treatments with better control of the disease and fewer side effects. We propose an antibody therapeutic as a novel approach to controlling excess cortisol that we believe can act across the entire patient population and that can work in concert with other medications. Our goal for this SBIR NIH grant is to initiate the necessary development work to make this new medicine possible.

皮质醇是一种类固醇激素，调节全身的各种过程，包括新陈代谢和免疫反应。它在帮助身体应对压力方面也有非常重要的作用。肾上腺中高水平的促肾上腺皮质激素（ACTH）刺激皮质醇的分泌，导致血液中皮质醇水平升高。长期摄入过多的皮质醇会导致一种称为库欣综合征的疾病，其特征是面部、胸部和腹部的体重迅速增加，与细长的手臂和腿形成对比，面部发红和圆圆，高血压，骨质疏松症，皮肤变化，肌肉无力，情绪波动，表现为焦虑，抑郁或易怒，口渴和排尿频率增加。当库欣氏综合征是由分泌过多ACTH的脑垂体肿瘤引起时，这种情况被称为库欣氏病。由于尚不清楚的原因，库欣氏病影响女性的比例几乎是男性的3比1。患有库欣氏病的女性可能会出现月经不调，面部、腹部和腿部毛发过度生长。如果不及时治疗，库欣氏病可能是致命的，首选的治疗方法是手术切除肿瘤而不损伤脑垂体的其余部分。当手术不可能或未能完全切除肿瘤时，通常需要药物来阻断过量皮质醇的影响。类固醇合成抑制剂、糖皮质激素受体阻断剂、卡麦角林，和生长抑素类似物在治疗库欣病患者方面确实有很大的不同，这些病人中有相当一部分从未得到充分的治疗。对于新型药物，更好地控制疾病和更少的副作用的治疗。我们提出一种抗体治疗剂，一种控制过量皮质醇的新方法，我们相信它可以在整个患者群体中发挥作用，可以与其他药物协同工作。我们的目标是这个SBIR NIH赠款是启动必要的开发工作使这种新药成为可能。