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，可调节整个身体的多种过程，包括新陈代谢和免疫反应，它在帮助身体应对压力方面也发挥着非常重要的作用。刺激皮质醇的分泌，导致血液中皮质醇水平升高，长时间内皮质醇过多会导致一种称为库欣综合征的疾病，其特征是体重快速增加，主要出现在面部、胸部和身体部位。腹部与细长的手臂和腿形成鲜明对比，脸色红润圆润，高血压、骨质疏松、皮肤变化、肌肉无力、情绪波动（表现为焦虑、抑郁或烦躁）以及口渴和排尿频率增加。一种分泌过多促肾上腺皮质激素的垂体肿瘤，这种疾病被称为库欣病，但由于尚不清楚的原因，库欣病对女性的影响比男性高近 3 至 3 倍。 1. 患有库欣病的女性可能会出现月经不调，并且面部、腹部和腿部毛发过度生长，如果不及时治疗，库欣病可能会致命，治疗方法是在不损害其他部位的情况下手术切除肿瘤。当手术不可能或无法完全切除肿瘤时，通常需要药物来阻止过量皮质醇的影响，而类固醇合成抑制剂、糖皮质激素受体阻滞剂、卡麦角林、和生长抑素类似物无疑对库欣病患者的护理产生了巨大的影响，库欣病是一种大量此类患者从未得到充分治疗，对新型药物的医疗需求显然未得到满足。我们建议采用抗体疗法作为治疗方法，以更好地控制疾病并减少副作用。我们相信控制过量皮质醇的新方法可以对整个患者群体起作用，并且可以与其他药物协同工作，我们的 SBIR NIH 拨款目标是启动必要的治疗。开发工作使这种新药成为可能。