Reinvention of the diagnostic algorithm and therapeutic options for reactivated toxoplasmosis (ToxoReTREAT)
Project leader: Dr. Tijana Štajner
Project collaborators: Dr. Jelena Srbljanović, Dr. Branko Bobić, Dr. Vladimir Dobričić, Dr. Anđelija Ilić, Dr. Dragana Vujić, Đorđe Zlatković, Olivera Lijeskić, Jelena Trajković
Project number: 7328
Duration of the project: 2023-2026.
Leading institution: Institute for Medical Research, University of Belgrade
Collaborating institutions: Faculty of Pharmacy, University of Belgrade, Faculty of Medicine, University of Belgrade, Institute of Physics Belgrade, University of Belgrade
Description of the project:
Toxoplasma gondii, the causative agent of toxoplasmosis, is a parasitic protozoan that infects almost a third of the global population. In cases of prolonged immunosuppression, reactivation of the infection occurs in chronically infected patients , which can be life-threatening. Reactivated toxoplasmosis (RT) is a particularly devastating complication in allogeneic hematopoietic stem cell recipients, who represent the fastest growing population of immunosuppressed patients in Europe. Despite this, there are still no guidelines for the diagnosis and treatment of RT. Moreover, the limited therapeutic options for RT are not only inadequate for allogeneic hematopoietic stem cell recipients due to pronounced myelotoxicity, but also ineffective because they only act on circulating parasites.
The main goal of the ToxoReTREAT project is to solve the problem of RT in the population of recipients of allogeneic hematopoietic stem cells using a multidisciplinary approach (medicine, pharmaceutical analysis, chemical industry); improve efficiency and reduce side effects; and the formulation of national guidelines for the diagnosis and treatment of RT. Namely, molecular monitoring of RT, isolation and characterization of T. gondii strains, identification of risk factors and evaluation of the effectiveness of standard treatment options will result in the formulation of National Guidelines for the diagnosis and treatment of toxoplasmosis in allogeneic hematopoietic stem cell recipients. The activity of newly synthesized and modified derivatives of acridine and acridone will be investigated both in vitro and in vivo experimental models of RT. T. gondii strains will be isolated from patients diagnosed with RT. Our research will identify at least one RT drug candidate with reduced toxicity and increased overall efficacy against T. gondii tachyzoites and bradyzoites, compared to standard therapy. We expect that the results of our project will arouse the interest of the pharmaceutical industry to engage in the development of new drugs for the treatment of toxoplasmosis. The sustainable transfer of knowledge gained through chemotherapy experiments will be contributed by the application of the freely available ImageJ software for the improvement of the automated assessment of the results of the experiments.
Тип пројекта:
National Projects