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Long-acting ghrelin for the treatment of cancer cachexia

长效生长素释放肽用于治疗癌症恶病质

基本信息

批准号：
9753044
负责人：
Tarik Soliman
金额：
$ 0.21万
依托单位：
EXTEND BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-24 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9753044
关键词：
Address Amino Acids Animal Model Animals Anorexia Anti-inflammatory Appetite Stimulants Biological Markers Biological Sciences Body Weight Body Weight decreased Cachexia Cancer Model Cancer Patient Canis familiaris Cessation of life Chronic Disease Chronic Obstructive Airway Disease Clinic Clinical Complex Congestive Heart Failure Consumption Coupled Cyclic GMP Data Development Dose Drug Kinetics Eating Energy Intake Enzyme-Linked Immunosorbent Assay FDA approved Fatigue Fatty acid glycerol esters Growth Half-Life Health Care Costs Heart Hindlimb Home environment Hormones Hospitalization Human Immune response Impairment Infection Inflammatory Intravenous Intravenous infusion procedures Laboratories Lead Life Expectancy Malignant Neoplasms Manufacturer Name Measures Medicine Methods Modeling Modification Muscle Patients Peptides Pharmaceutical Preparations Pharmacodynamics Pharmacotherapy Phase Plasma Process Property Pump Quality of life Rattus Regimen Rivers Rodent Model Self Administration Small Business Innovation Research Grant Somatotropin Syndrome Testing Therapeutic Effect Therapeutic Uses Thinness Time Toxic effect Toxicokinetics Toxicology Treatment-Related Cancer Weight Weight Gain Work absorption acyl group appetite loss base cGMP production cancer cachexia cancer therapy chemotherapy clinical candidate college deacylation efficacy testing food consumption ghrelin immunogenicity improved increased appetite infection risk inflammatory marker lead candidate lean body mass manufacturing process muscle form outcome forecast phase 1 testing receptor binding reduce symptoms response scale up skeletal muscle wasting subcutaneous

项目摘要

Project Summary Cachexia is a complex syndrome characterized by involuntary weight loss and skeletal muscle wasting that leads to fatigue, weakness and a loss of appetite that is not reversed by increased caloric consumption. More than half of all cancer patients develop cachexia and it is responsible for more than 20% of all cancer deaths. Numerous complications associated with cachexia include an impaired response to drug treatment, an increased chance of infection, a poor prognosis and a decreased quality of life. Currently, there are no FDA- approved treatments for cancer cachexia, but the hormone ghrelin has recently emerged as a molecule with great potential. Several studies in both animals and humans have shown that ghrelin increases food intake, stimulates the release of growth hormone, increases muscle mass, and reduces markers of inflammation. However, the use of ghrelin as a treatment is limited for several reasons: 1) ghrelin must be dosed 2-3 times daily to see efficacy due to its inherently short half-life of 30 min; 2) deacylation of ghrelin to an inactive form occurs in less than 5 min; and 3) ghrelin is currently dosed intravenously to see a therapeutic effect. The studies completed during SBIR Phase I address each of these issues, resulting a long-acting ghrelin derivative that could be dosed subcutaneously once every other day in rats to reverse the effects of cachexia in the Yoshida rat model. The studies proposed in this Phase II application will investigate the ability of our long- acting ghrelin to ameliorate cachexia in two additional models. Methods for cGMP production of the long-acting ghrelin will be put in place. We will perform IND-enabling GLP toxicity and immunogenicity studies using the cGMP material. These studies are needed prior to beginning human trials. Once fully developed, this long- acting ghrelin derivative would provide a patient-friendly cachexia therapy that would significantly improve the prognosis and quality of life in patients with cancer and also in patients with other chronic disorders such as congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD).

项目总结