Summary
Develop next-generation anthelmintics using Bacillus thuringiensis crystal (Cry) proteins to treat parasitic gastrointestinal nematodes, aiming for first-in-human trials.
B. thuringiensis crystal proteins as powerful next-generation anthelmintics
US · IL
NIH
grant
awarded
#nih-5R01AI056189-21
What they want
The project aims to develop Cry protein anthelmintics that meet World Health Organization (WHO) Target Product Profiles (TPPs) for GIN anthelmintics. This involves identifying synergistic combinations among six anthelmintic Cry proteins in vitro and in vivo against all three classes of GINs in rodents, testing fit-for-purpose formulation strategies for improved gastric resistance and efficacy, and generating hybrid Cry proteins by swapping domains for superior efficacy. The best Cry protein combinations will be tested against multi-drug-resistant dog hookworms in vitro and in vivo to select a single lead candidate for GLP-toxicological studies as a prelude to first-in-human trials.
Deliverables
- Identification of synergistic combinations of anthelmintic Cry proteins
- Identification of hybrid Cry proteins with superior efficacy
- Fit-for-purpose formulation strategies for improved gastric resistance and anthelmintic efficacy
- Selection of a single lead candidate Cry protein combination for GLP-toxicological studies
- Safety studies for progression of a lead anthelmintic to clinical trials
Technical requirements
- Meet World Health Organization (WHO) Target Product Profiles (TPPs) for GIN anthelmintics
- Target all three major human GIN classes (hookworms, whipworms, roundworms)
- Achieve high efficacy, low dose, and low cost
- In vitro and in vivo testing in rodents against all three GIN classes at a Step 1 TPP of 5 mg/kg
- Testing against multi-drug-resistant dog hookworms
- Delivery via IBaCC (Inactivated Bacteria with Cytosolic Crystal(s))
- GLP-toxicological studies
