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Activin A antagonist for treatment of cancer-associated cachexia

激活素 A 拮抗剂用于治疗癌症相关恶病质

基本信息

批准号：
9046615
负责人：
BRADLEY T MESSMER
金额：
$ 22.5万
依托单位：
ABREOS BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-25 至 2016-03-24
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9046615
关键词：
Activin Receptor Activins Adenocarcinoma Cell Adipose tissue Adverse effects Anemia Angiotensin-Converting Enzyme Inhibitors Binding Biological Models Cachexia Cancer Center Cell Line Cell Nucleus Cell surface Cessation of life Clinical Collaborations Colon Adenocarcinoma Comorbidity D Cells Data Development Diagnostic Neoplasm Staging Disease Disulfides Drug Kinetics Erythrocytes Erythropoiesis Exhibits Extracellular Domain Faculty Family Funding GDF8 gene Gene Targeting Goals Growth Hemorrhage Implant In Vitro Legal patent Ligand Binding Ligands Light Link Malignant Neoplasms Mediating Mediation Methyl Green Michigan Modeling Mus Muscle Oranges Osteoporosis Outcome Patients Phase Phase II Clinical Trials Phosphorylation Phosphotransferases Prevention Proteins Qualifying Research Personnel Rights Secure Signal Transduction Skeletal Muscle Small Business Innovation Research Grant Small Business Technology Transfer Research Structure of thyroid parafollicular cell Testing Therapeutic Time Transforming Growth Factor beta Type I Activin Receptors Type II Activin Receptors Universities Wasting Syndrome activin A base bone bone loss bone morphogenetic protein receptors cancer cachexia cancer type chemotherapy cryptic protein fighting in vivo inhibitor/antagonist mouse model novel palliative pre-clinical prevent professor public health relevance receptor receptor binding research study skeletal transcription factor tumor wasting

项目摘要

DESCRIPTION (provided by applicant) Cachexia is a major cause of suffering and death among patients with late stage cancers and the current treatment options are limited and ineffective. We have identified a novel Activin A inhibitory protein, Cryptic, that can potentially eliminate the muscle wasting activity of Activin in cachexia. Activin A has been previously validated as a target using other ligand traps, such as the Activin receptors ActRIIA and ActRIIB, but those molecules are promiscuous in binding to other TGF-beta family ligands which leads to compromising side effects. Cryptic exhibits a far more targeted activity towards Activins and therefore may be an ideal therapeutic for Activin mediated conditions. Preliminary data with an Fc fusion, Cryptic-Fc, has shown in vivo efficacy in an osteoporosis model system with both bone and muscle restorative effects observed. The goal of this project is to test Cryptic-Fc in a mouse model of cachexia. Mice implanted with the C26 colon adenocarcinoma cell line, which rapidly manifest cachexia, will be used to evaluate both prevention as well as the reversal of cachexia. In specific aim 1, various Cryptic deletion constructs will be prepared and analyzed for Activin binding and pharmacokinetics to identify optimal candidates for development. In specific aim 2 qualified Cryptic-Fc constructs will be tested in the mouse model. If successful, these studies will provide proof of concept for Cryptic-Fc in the treatment of cachexia and pave the way for more thorough pre-clinical development. This project is a collaboration between Abreos Biosciences and Dr. Martinez-Hackert, Assistant Professor at Michigan State University and the discoverer of Cryptic's Activin inhibiting functions. Abreos has secured exclusive rights to develop Cryptic for this and other indications.