In this project update, Dr. Carlos Muskus outlines the discovery of three important proteins which may help find better treatments for a neglected disease that strikes millions of people every year.
Leishmaniasis, which is one of the most neglected tropical diseases in the world, infects more than two million people in 97 countries. There are no available vaccines to prevent the disease, and the treatments can cause severe side effects, including death. Furthermore, drug-resistant parasites are causing major problems in many endemic countries. For these reasons, there is an urgent need for new, safe and inexpensive drug compounds.
Since our last update in July 2015, we have been moving forward in several key areas: 1) we are conducting further research on the findings from Drug Search for Leishmaniasis, which has identified three important proteins, 2) we are publishing and presenting our results, and 3) we are planning for a second phase of the project, which may also involve World Community Grid.
Current Lab Research
As mentioned in our previous update, we have performed in vitro testing on 10 drug compounds which showed promise based on the results of Drug Search for Leishmaniasis. Four of these compounds showed good results. We are setting up new experiments to confirm these results, and have ordered more compounds which should arrive in a few weeks, at which time we can begin the next round of testing.
We also identified three proteins which had hits with several drug compounds in our library. We will refer to these three proteins as Protein 1, Protein 2, and Protein 3 until our results are published. Interestingly, these proteins had previously been identified as possible drug targets, both in humans or microorganisms.
In our initial testing, one of the drug compounds was a hit by the docking screening against Protein 1. We plan to test the most promising compounds in in vitro experiments. If we get similar results, we will plan to perform in vivo experiments.
Proposal and Search for Funding
Recently, we completed a proposal for a study to demonstrate that the anti-leishmanial effect of a particular compound was through the inhibition of Protein 1. Our proposal was submitted to the main Colombian funding agency, Colciencias, in collaboration with Dr. Cristina Nonato at the University of Sao Paulo. Dr. Nonato's lab produced the recombinant protein. Finding funding for our work is a challenge, but once we obtain funding for this study, we will set up enzymatic assays to continue to study the interaction between Protein 1 and the particular compound.
Presenting and Publishing Our Results
Findings from Phase 1 were presented by Rodrigo Ochoa, one of the research team members, at the XVI Congress of the Colombian Association of Parasitology and Tropical Medicine, which was held in Santa Marta, Colombia in October 2015. At this event, Rodrigo presented the project findings along with the in vitro testing results obtained to date. We have produced a paper describing the most relevant results from the project, and it is currently being reviewed by each author. We hope to submit the paper to an international journal in in a few weeks. Once the paper is published, we will share details of it on World Community Grid. And after publication, we will move forward with the second phase of this project on World Community Grid, during which we will analyze the Phase 1 results.
Team News
Team member Rodrigo Ochoa won two scholarships last year to travel to a workshop and a congress. He participated in a workshop entitled "Bioinformatics: Computer Methods in Molecular and Systems Biology" in Trieste, Italy at the International Center for Genetic Engineering and Biotechnology, and in the Latin American Conference on Mathematical Modeling of Biological Systems at the University of Buenos Aires in Argentina.
We are very grateful to all World Community Grid volunteers who participated in Phase 1 of this project. We are excited to begin planning for Phase 2, after the results from Phase 1 are published, and hope you will continue to support us as our research continues to move closer to eradicating leishmaniasis.