Targeted drug treatment for cutaneous leishmaniasis
Cutaneous leishmaniasis (CL) is a neglected tropical disease, closely linked to levels of poverty. CL is caused by a parasite spread via the bite of infected blood-eating sandflies, and causes ulcers on the skin which can leave permanent disfiguring scars. CL is endemic in subtropical and tropical regions, and estimates suggest up to a million new cases appear each year in regions where the vector lives. Climate change is increasing the range of the vector and putting more people at risk of infection. Current therapies can be costly and toxic, and require ongoing and painful injections. “This is often infeasible or unavailable for many patients in remote areas,” explains Sanjeev Krishna, professor emeritus of Molecular Parasitology and Medicine at St George’s, University of London, and TT4CL project coordinator. In the EU-funded TT4CL project, a multidisciplinary consortium of researchers worked to bring a new and promising oral treatment for CL to clinical trial; this treatment could overcome some of the existing therapeutic barriers and improve the lives of millions of people around the world. The new drug, Oleylphosphocholine (OlPC), is an immediate treatment for CL and is currently the only oral drug treatment being developed to target the condition. “The phase 1 clinical trial showed that OlPC in our formulation was safe and tolerated in adult recipients and determined a No Adverse Effect Level (NOAEL),” says David Clark, project manager and postdoctoral researcher at St George’s, University of London. “A safe dose will be the basis of future studies,” he adds.
Targeting leishmania parasites
OlPC targets leishmania parasites, though the exact biochemical mechanism of action is still to be defined in detail. In the TT4CL project, the researchers performed a combination of animal model studies along with a phase I safety study in humans at the Tropical Medicine Institute of the University of Tübingen. The team also carried out drug formulation investigations to achieve an effective and chemically stable dose – which therefore does not require specialist storage or transportation. Project partners from Belgium, Germany, Iran, the Netherlands and the United Kingdom were involved in the project.
Achieving a stable and effective formulation
The team used data from the animal and formulation studies to guide the development of the clinical trial protocol, which proved successful. “The animal studies conducted by Dr Van Bocxlaer at the University of York showed that the size of skin lesions is reduced and the number of parasites in the skin is significantly reduced,” notes Clark. The drug formulation, carried out by Avivia in the Netherlands, was shown to be stable in simulated harsh environmental conditions for at least 12 months. The next steps include assessing extended pharmacokinetics and determining safety and tolerability in subjects with leishmania parasite infections. “Ideally we would pursue a phase I/II study which would include efficacy in humans,” says Peter Kremsner, coordinator of the clinical trial.
A potentially game-changing treatment for CL
The consortium believes that the treatment could increase the cure rate for this neglected disease, particularly as it is more accessible to those in need, including marginalised communities. “Having a drug that is orally available, chemically stable, affordable and, crucially, accessible, would be game-changing,” concludes Krishna.
Keywords
TT4CL, cutaneous leishmaniasis, leishmania, parasites, oral, treatment
