Drugs in development for toxoplasmosis: advances, challenges, and current status.
Toxoplasma gondiicauses 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 againstT. gondiitissue 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.
Division of Infectious Diseases, Oregon Health & Science University.
P Holland
PH
Alday
Division of Infectious Diseases, Oregon Health & Science University; Portland Veterans Affairs Medical Center, Portland, OR, USA.
Joseph Stone
JS
Doggett
D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D014122:Toxoplasma / Q000187:drug effects*; D014123:Toxoplasmosis / Q000188:drug therapy* / Q000469:parasitology
D000981:Antiprotozoal Agents
Apicomplexa; Toxoplasma gondii; experimental medicine; mechanism of action; preclinical medicine; therapeutics