权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of an Orally Available Therapeutic for Neutralizing C. difficile Toxin B

中和艰难梭菌毒素 B 的口服疗法的开发

基本信息

批准号：
10697280
负责人：
Mohamed Seleem
金额：
$ 27.45万
依托单位：
NECTAGEN, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-05 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10697280
关键词：
Acute Affinity Antibiotic Therapy Antibiotics Antibodies Bacteria Binding Biological Biological Assay Cells Cessation of life Chronic Clinical Clostridium Clostridium difficile Collection Development Diarrhea Digestion Dose Drug Kinetics Enteral Enzymes Escherichia coli Exotoxins Formulation Freeze Drying Future Goals Growth Hand In Vitro Infection Injections Intervention Intestines Intoxication Intravenous infusion procedures Lead Mammalian Cell Metronidazole Monoclonal Antibodies Morbidity - disease rate Oral Oral Medicine Oral cavity Pain Pathogenicity Patients Peptide Hydrolases Price Production Prophylactic treatment Proteins Recurrence Research Resistance Route Solubility Structure Therapeutic Toxin Trypsin United States Vancomycin Work acute care antibody mimetics antitoxin bactericide biophysical properties capsule chymotrypsin cost efficacy evaluation fecal transplantation gut microbiome high risk improved innovation inpatient service intravenous administration manufacturing cost microbiome mortality mouse model nanobodies novel novel strategies preservation prevent relapse prevention therapeutic candidate uptake

项目摘要

Infection with the bacterium C. difficile is the most common and increasingly prevalent cause of diarrhea. In the United States, cases of C. difficile infection (CDI) are estimated to number 500,000 annually and to result in an estimated 15,000 to 30,000 deaths. The cost of these cases is thought to exceed $4.8 billion annually. CDI continues to cause discomfort, serious illness and sometimes death despite several available lines of treatment. Current treatments include antibiotics, fecal transplant, and an antibody. The antibody represents a new approach to treating CDI by neutralizing toxins secreted by C. difficile rather than killing the bacteria or stopping their growth. One limitation of the antibody is that it needs to be delivered via an injection instead of taken by mouth. The long-term objective of the proposed research is to develop a new treatment that binds to and neutralize the toxins made by C. difficile and that may be taken by mouth. The treatment is based on a novel nanoCLAMP protein similar to antibodies in its structure and potential to neutralize C. difficile toxin. However, compared with antibodies, nanoCLAMPs are much more resistant to the destructive effect of digestive enzymes. Resistance to digestive enzymes may enable patients to take this medicine orally and avoid a painful injection. The objectives of the current proposal are to 1. Select lead anti-TcdB nanoCLAMPs with TcdB-neutralizing activity and developable biophysical properties. 2. Assess dose-exposure relationship for anti-TcdB nanoCLAMPs in enteric capsules. 3. Evaluate efficacy in acute and recurrence mouse models of C. difficile infection.

艰难梭菌感染是腹泻最常见和日益流行的原因。在