Anti-malarial drugs targeting PfGARP

Overview

Plasmodium falciparum malaria is a leading cause of morbidity and mortality in developing countries, infecting hundreds of millions of individuals and killing more than 300,000 children each year. Certain parasite strains are resistant to all anti-malarial drugs, and the anti-malarial drug discovery pipeline is alarmingly limited. We have developed small molecule drugs for the treatment of malaria that target P. falciparum glutamate-acid-rich protein (PfGARP).

 Market Opportunity

P. falciparum, the most severe form of malaria, is responsible for the majority of deaths associated with the disease. Artemisinin and derivatives such as artesunate are widely used in severe and uncomplicated P. falciparum, and artesunate is considered to be the best drug available for the treatment of severe and complicated malaria. Unfortunately, the spread of parasites resistant to the artemisinin family of compounds underscores the urgent need to identify both new anti-malarial drugs and novel approaches to identify them.

Innovation and Meaningful Advantages

We recently discovered P. falciparum PfGARP as a parasite antigen recognized by antibodies in the plasma of children who are relatively resistant—but not susceptible—to malaria caused by P. falciparum. Antibodies to the highly invariant carboxyl terminal of PfGARP inhibited parasite growth in vitro by 99%, compared with controls, by triggering a “kill switch” in malarial cells that causes trophozoite-stage parasites to self-destruct.

Our treatment for P. falciparum malaria consists of small molecule drugs that activate apoptosis in cells that express PfGARP without activating apoptosis in subject host cells or in parasite cells that do not express PfGARP. This demonstrates specificity of the mechanism of action, as well as evidence for limited off-target toxicity. Since there has not yet been an anti-malarial drug that specifically activates apoptosis, our invention represents a new class of anti-malarial drugs.

Unlike existing anti-malarial drugs, which exert their effect via internal cellular targets, our novel drugs bind to PfGARP on the exofacial surface of red blood cells. The drugs can be administered orally, subcutaneously, transdermally, or topically. They can also be formulated for inhalation or even dissolved or suspended in sterile water.

Collaboration Opportunity

We are interested in exploring 1) startup opportunities with investors in the drug delivery space; 2) research collaborations with leading pharmaceutical companies to develop this treatment; and 3) licensing opportunities for drug delivery companies.

Principal Investigator

Jonathan Kurtis, MD, PhD

Stanley M. Aronson Professor of Pathology and Laboratory Medicine

Brown University

jonathan_kurtis@brown.edu

https://vivo.brown.edu/display/jkurtis

IP Information

PCT Application PCT/US2022/018169, Published January 9, 2022

Publication

Raj DK, Das Mohapatra A, Jnawali A, et al. Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria. Nature. 2020;582(7810):104-108. doi:10.1038/s41586-020-2220-1

Website

http://brown.technologypublisher.com/technology/48752

Contact Information

TTO Home Page: http://brown.technologypublisher.com

Name: Andrew Bond

Title: Director of Business Development – Life Sciences

Email: andrew_bond@brown.edu