A new University of Kentucky study may lead to a new treatment against Toxoplasma gondii, the parasite that causes toxoplasmosis.
Millions of people carry the parasite T. gondii, but very few have symptoms because the immune system usually keeps the parasite from causing illness. However, toxoplasmosis can have severe consequences for women newly infected during pregnancy and anyone with a compromised immune system.
Occasionally, toxoplasmosis can cause fever, unfamiliar symptoms, and tender lymph nodes, as well as eye problems, visual impairments, throat infection, poor mental coordination, and birth defects.
In previous research, Matthew Gentry, from the Department of Molecular and Cellular Biochemistry at the University of Kentucky, identified an enzyme in T. gondii called TgLaforin, which he hypothesized was critical in allowing the parasite to access energy from a carbohydrate storage molecule. Then, in the new study published in the Journal of Biological Chemistry, Gentry and his team announced they have developed a new drug that inhibits TgLaforin with the goal of preventing enzymes from accessing and providing energy to the parasite.
While there are FDA-approved drugs to treat the symptoms of toxoplasmosis, no current therapeutics target the cyst form of the parasite.
The new discovery was made possible thanks to the multidisciplinary collaboration of experts from four labs, says Gentry.
Robert Murphy, from the Department of Molecular and Cellular Biochemistry at the University of Kentucky, conducted initial experiments that characterized TgLaforin and provided a baseline for understanding the enzyme’s function. Then, researcher Tiantian Chen generated models of TgLaforin using a new program called AlphaFold2, which is an artificial intelligence algorithm that provides valuable insights into research. Chen generated models that provided a picture of the enzyme that demonstrated TgLaforin was a unique and possible drug target.
Jianping Lin, a postdoc researcher, then used information generated by Murphy and Chen in combination with novel techniques in chemistry to generate the first version of a future anti-Toxoplasma drug.
“I was excited to find that the drug was effective against TgLaforin in test tubes and that it prevented TgLaforin from performing its normal activity,” said Murphy.
Future work from these labs will test the drug on animals, hoping to move eventually to clinical trials on human.
