A new approach to treating a common parasitic disease called toxoplasmosis allows researchers to turn off genes within a parasite, slowing the parasite's growth.
Scientists at the University of Chicago Medicine are working toward a cure for the illness, which affects about 2 billion people across the world, according to the Toxoplasmosis Research Institute and Center. Signs of toxoplasmosis include flulike symptoms, such as monthlong muscle pains or aches; swollen lymph glands; and damage to organs, including the brain or eyes.
"[Toxoplasmosis] is a treatable but not yet curable disease. … We can make the outcomes of the infection much better," said Dr. Rima McLeod, an expert on toxoplasmosis and professor at the U. of C. Medicine. McLeod, who is also president of the Toxoplasmosis Research Institute, is one of the authors of a paper about the treatment that was published Aug. 13 in the online version of Proceedings of the National Academy of Sciences. The print version is expected to appear in a few weeks.
The new genetic treatment decreased the number of viable parasites in mice by more than 90 percent, according to the study.
The research involved using a transductive peptide carrier and an antisense molecule, or phosphorodiamidate morpholino oligomer cargo.
The peptide carries the antisense molecule through multiple barriers, such as those around the eyes and the brain, to bind with the parasite's RNA, preventing the parasite's RNA from being turned into a protein.
"The second part of the system, the antisense part, shuts off the gene. For a gene product to be generated, the gene has to be transcribed to form RNA and translated into a protein. Antisense blocks the RNA (from being) translated to a protein," said Bo-Shiun Lai, 20, a U. of C. student who works in McLeod's lab at the institute. Lai helped develop the study as part of his senior honors thesis.
The method is "a very practical way of interfering with the survival of something that isn't wanted. It's a step. It's not perfect yet," McLeod said. "[The carrier] brings the cargo to where it needs to go to be active, from the inside to the nucleus of the parasite, to a place where the genes are turned on and off."
The researchers tested five different antisense molecules, including one that blocked the parasite's ability to make folate, which is essential for growth; another that prevented it from making lipids, which contribute to energy storage; and a third that "substantially shut down" the parasite's DNA synthesis, which helps it to grow.
Craig W. Roberts, a professor of parasitology at the Strathclyde Institute of Pharmacy & Biomedical Sciences at the University of Strathclyde in Glasgow, Scotland, called the results "very encouraging."
"This study is useful because the treatments used in the experiments could be translated directly to humans and help to find essential targets in toxoplasmosis," Roberts said. "We can identify the biological processes essential to the survival of the parasite, but that are not required by humans. We don't want to target something a human has also. The pathways are very promising for the development of drugs against it."
The new approach could also potentially treat genetic or eye disorders, and cancers, McLeod said.Copyright © 2014, Los Angeles Times