Drug Repurposing for Malaria Chemoprotection

Informacje na temat projektu

REUSE4MALARIA

Identyfikator umowy o grant: 713691

DOI

10.3030/713691

Projekt został zamknięty

Data podpisania przez KE 4 Listopada 2016

Data rozpoczęcia 1 Grudnia 2016

Data zakończenia 31 Maja 2018

Finansowanie w ramach

• EXCELLENT SCIENCE - European Research Council (ERC)

Koszt całkowity

€ 145 500,00

Wkład UE

€ 145 500,00

Koordynowany przez

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Portugal

Periodic Reporting for period 1 - REUSE4MALARIA (Drug Repurposing for Malaria Chemoprotection)

Okres sprawozdawczy: 2016-12-01 do 2018-05-31

Podsumowanie kontekstu i ogólnych celów projektu

Malaria is a deadly disease caused by Plasmodium spp. causing ~500,000 million deaths yearly (WHO 2017). Current treatments have shortcomings, such as, i) limited number of effective drugs, ii) adverse side effects and restricted use iii) development of drug resistance, and iv) restrictive mechanisms of action. Despite current advances in novel parasite-directed antimalarials, which hold much promise and are currently in the clinical pipeline, there is still a need for alternative approaches. Host directed chemotherapy is a reasonable and alternative approach to combat malaria, as it would address several of the shortcomings of current treatments (Prudencio & Mota 2013).
Our ERC-funded research uncovered a novel mechanism of action that can be targeted for malaria chemoprotection, with fewer side effects and reduced propensity to generate parasite resistance, on which we filed for IP protection. Furthermore, we have identified a set of likely drug candidates already validated in the clinic, which are likely candidates for malaria chemoprotection. In fact, our data indicates the widely used anti-diabetic drug Metformin significantly affects parasite growth. This PoC funding allowed for the exploitation of this concept. Indeed, our data show that prophylactic treatment of mice with Metformin prior to infection with Plasmodium sporozoites leads to a reduction in parasite burden in the liver, thus reducing the parasite load in the blood. Furthermore, combining Metformin treatment in conjunction with another antimalarial leads to a synergistic reduced liver burden and subsequent attenuation of virulence.