Therapeutics/Drugs

Hasan Uludag of RJH Biosciences in Canada will develop an affordable immunotherapy system based on genome-integrating transposons that works inside the body for the treatment of a wide variety of diseases such as cancer and diabetes. Emerging immunotherapies offer promising treatment for many diseases, but they require genetic modification of immune cells outside the body, and are thus labor intensive and expensive, limiting their utility in developing countries. They will use engineered nanoparticles in a new approach to immunotherapy that modifies immune cells inside the body.

Pietro Alano of the Instituto Superiore de Sanità in Italy will develop a biochip that mimics the midgut of the Anopheles mosquito and can be used to more easily and quickly test candidate anti-malarial compounds for blocking transmission of the causative Plasmodium parasite. Malaria is a potentially fatal infection caused by parasites transmitted between humans through the bites of infected mosquitoes. When a mosquito bites an infected person, immature Plasmodium gametocytes enter the mosquito and transform into an invasive ookinete stage in its midgut.

The aim of the research is to identify selective modulators of the TB bacteria, Mycobacterium tuberculosis (Mtb), to support development of newer, more effective therapies.

The propensity of malaria parasites to develop resistance motivates the ongoing discovery and development of antimalarials with new modes of action. Heinrich Hoppe’s research focuses on employing novel bioassays to find inhibitors of Arf1, a GTPase that regulates protein secretion, in order to validate it as an antimalarial drug target

This research proposes to apply new protocols that have been developed at RUBi combined with traditional computational drug discovery approaches to further improve our understanding of rational drug discovery in the context of tuberculosis and malaria. Additionally, where applicable, it aims to identify novel hits from African natural products against these diseases as screening of them may lead to the development of novel pharmaceutics in Africa

The project aims to discover molecular scaffolds that could be forerunners of EAEC therapeutics. Following a small molecule library screen, the team is evaluating hits, determining their mechanisms of action and their potential to be progressed as drug candidates. The group will also apply their anti-biofilm screen to other small libraries with a view to increasing the repertoire of promising leads against EAEC and other neglected enteric pathogens.

This project builds on intra-African and international (pharmaceutical companies, academic institutions) collaborations to identify medicinal chemistry starting points from the screening of target-based chemical libraries against the causative agents of malaria, leishmaniasis and Human African Trypanosomiasis (HAT), also known as sleeping sickness.

The emergence of drug resistance has rendered most clinically used drugs ineffective. There is, therefore, the need to discover new, safe, effective and novel chemo types with new modes of action. This project seeks to continue medicinal chemistry efforts on a chemical class identified from the MMV Pathogen box to develop an early lead with in vivo antitubercular/antimalarial activity as a proof-of-concept

Darryl Russell of the University of Adelaide in Australia is seeking safer contraceptives that block ovulation without altering hormone levels and cause fewer side effects using an automated in-vitro screening platform that measures cell adhesion in the cumulus-oocyte complex, which is required to release the oocyte from the ovary. In Phase I, they built the screening platform by isolating cumulus-oocyte complexes from mice, culturing them in fibronectin-coated multi-well plates, and quantifying adhesion in a 96-well plate format using an automated assay.

Pia Wintermark of McGill University in Canada and Cally Tann of the London School of Hygiene & Tropical Medicine in the United Kingdom will establish a pilot cohort in Uganda of term newborns who suffered from asphyxia at birth, which means that their brain and other organs did not receive enough blood or oxygen, and conduct a clinical test of a novel neurorestorative agent (i.e., to repair brain injuries) to see if it can improve early brain development in this setting.