LeadtoTreat aims at developing a platform for future treatment of multidrug-resistant microbial infections, enabling targeted delivery of novel lead compounds with low drugability, as well as synergistic combinations of antibiotics and potentiators in a nanoformulation.
The long-term vision of LeadtoTreat is to contribute to a radical shift in the treatment approach for antibiotic-resistant bacteria, by developing strain selective, targeted nanoformulations containing synergistic combinations of antibiotics and potentiators, leading to a platform and process that can rapidly increase the number of antibiotic treatments available.
LeadtoTreat will address two major challenges in the treatment and eradication of microbial infections:
primary antibiotic treatments and
to drugs of last resort.
or unfavourable biodistribution of
promising novel lead compounds.
- Identify synergistic antibiotic combinations and potentiator/antibiotic combinations.
- Develop novel targeting moieties for MRSA infection and inflammation based on nanobodies and short peptides.
- Develop polyphosphazene polymer-based nanoformulations, loaded with selected antibiotics and potentiators.
- Prove safety and efficacy in vitro and in vivo against MRSA
A toolbox of novel targeting nanoformulations containing antibiotics and/or potentiators enables selection, rapid adjustment and assembling in a modular approach to meet the challenges presented by novel bacterial mutations or strains, as they appear in the clinics. MRSA will be used as a first clinical indication.
The complementary expertise of the partners spans the entire value chain from drug screening to safety and efficacy testing.
A broad library of MRSA strains will be used to screen and identify synergistic antibiotic combinations and potentiator/antibiotic combinations.
Promising antibiotics and synergistic combinations will be formulated with polyphosphazene polymers into nanoformulations.
To redirect the antibacterial nanoformulations towards the targeted pathogen, novel short peptides and nanobodies for targeting MRSA will be identified, validated and produced. These novel targeting ligands will then be covalently attached to the nanoformulation surface.
Safety & Efficacy
To evaluate the performance of the novel targeting nanoformulations, in vitro and in vivo safety and efficacy will be assessed.