TY - JOUR
T1 - Drugs in development for toxoplasmosis
T2 - Advances, challenges, and current status
AU - Alday, P. Holland
AU - Doggett, Joseph Stone
N1 - Publisher Copyright:
© 2017 Alday and Doggett.
PY - 2017/1/25
Y1 - 2017/1/25
N2 - Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.
AB - Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.
KW - Apicomplexa
KW - Experimental medicine
KW - Mechanism of action
KW - Preclinical medicine
KW - Therapeutics
KW - Toxoplasma gondii
UR - http://www.scopus.com/inward/record.url?scp=85011654043&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011654043&partnerID=8YFLogxK
U2 - 10.2147/DDDT.S60973
DO - 10.2147/DDDT.S60973
M3 - Review article
C2 - 28182168
AN - SCOPUS:85011654043
SN - 1177-8881
VL - 11
SP - 273
EP - 293
JO - Drug Design, Development and Therapy
JF - Drug Design, Development and Therapy
ER -