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赛酮，可调节整个人体的各种过程，包括代谢和免疫激素。它在帮助身体应对压力方面也具有非常重要的作用。肾上腺中高水平的肾上腺皮质骑马（ACTH）刺激皮质醇的分泌，导致皮质醇的血液水平升高。长时间的皮质醇太多导致一种称为库欣综合症的疾病，其特征是体重快速增长，主要在面部，胸部和腹部与细长的手臂和腿部形成鲜明对比，脸色高而圆形，高血压，骨质疏松性，骨质骨化，皮肤变化，肌肉变化，肌肉疲软，焦虑，抑郁，抑郁，抑郁，抑郁，抑郁，抑郁，抑郁，抑郁或提高率和频率第三和频率。当库欣综合症是由垂体过多的垂体肿瘤引起的，该病情被称为库欣氏病。由于不清楚的原因，库欣氏病比男性更频繁地影响女性。库欣氏病的女性可能经历不规则的月经化，脸部，腹部和腿部头发过多。剩下的未治疗，库欣病可能是致命的，首选的行动是手术切除肿瘤而不会损害其余的垂体。如果无法进行手术或无法完全切除肿瘤，则通常需要药物来阻止多余的皮质醇的作用。而类固醇合成抑制剂，糖皮质激素受体阻滞剂，Cabergoline，但生长抑素类似物无疑对库欣氏病的患者的护理产生了很大的影响，这些患者中有大量的人从未得到充分治疗。有明显未满足的小说的医疗需求更好地控制疾病和更少的副作用的治疗方法。我们提出一种抗体疗法作为我们认为可以在整个患者人群中行动的新型控制超过皮质醇的方法可以与其他药物一起工作。我们这项SBIR NIH赠款的目标是启动必要的开发工作使这种新药物成为可能。