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Discovery shows promise as a new treatment for toxoplasmosis

18.11.2003


A multi-centre research team from the UK and the USA has discovered the first method to deliver medication directly into the encysted stage of the infectious parasites that cause toxoplasmosis and a novel target for medicines in the parasite. It has major implications for the way that we treat this devastating disease as it could lead to new medications and approaches to better tackle it. The study will be published online on November 17 by the Proceedings of the National Academy of Sciences (PNAS).



Toxoplasmosis is a parasitic infection from the ’apicomplexan’ family, which includes the causes of malaria and cryptosporidiosis. The disease is caused by a single celled organism called Toxoplasma gondii and is spread by cats and by eating undercooked meat. Toxoplasmosis is a common disease and can cause devastating problems for those with weakened immune systems, or when transmitted from mother to unborn child. It can lead to blindness, retardation and even death.

Professor David Rice, from the Department of Microbiology and Biotechnology at the University of Sheffield, was involved in the study. He explains, "Toxoplasma infections are especially difficult to treat because they recur. The disease operates in two stages, a proliferative stage and a latent stage. During the proliferative stage the infection can be treated, although there are many problems with available medicines, but the illness then progresses to a latent stage, where the cysts form that hold the parasites in a less active state. These cysts are untreatable as scientists can’t get medication inside the cyst. The cysts eventually rupture and release proliferating parasites, which can cause a recurrence of the illness if the immune system is weakened and in those with eye disease. Such recurrences can cause severe damage to the eye and nervous system."


The research team, led by Professor Rima McLeod, M.D. professor of ophthalmology and visual sciences at the University of Chicago, have a found a new method for delivering medicines that kill the parasites in the active stage and a new method for delivering medicines to kill them whilst they are in the active or latent stage.

The research began in 1996 when scientists at Stanford University discovered that short chains of arginine, a naturally occurring amino acid, could pass through human and mouse biological membranes, and could carry other molecules with them.

The new finding reported here means that for the first time scientists could have a way to deliver many medications through the host cell membranes and into cysts containing toxoplasma, directly to the parasite. Professor McLeod and her team set about looking more closely at the T. Gondii organism, to find a medication that would effectively kill the parasite without being toxic to humans.

Her team discovered an enzyme, enoyl reductase, that is not the same in animals and is vital to the survival of the parasite. The research team then identified a common antiseptic, triclosan, which had been found to affect enoyl reductase in bacteria and found it could kill the parasites responsible for toxoplasmosis and malaria but delivery was problematic. Triclosan is included in toothpaste, skin creams and mouthwash.

The triclosan was linked to the arginine chains in order to get the medication through several biological membranes to the parasites in cells and to the parasites within cysts. The cysts contain the parasites in their latent form. The team found that this method successfully inhibited the active parasite in mice and in tissue culture.

Professor McLeod says, "This discovery of the transporter is quite remarkable as no current antimicrobial compound can eliminate parasites in cysts. The discovery raises the possibility of better treatments for active infection and a new approach for treating latent infection in the eye by applying a lotion containing triclosan or other antimicrobials bound to a transporter which would carry them into the eye. If such treatment could eradicate the parasite in its latent form we could stop it from recurring. New targets such as enoyl reductase may provide a major step forward in identifying better treatments for active disease that causes much suffering as well as loss of life."

Lorna Branton | alfa
Further information:
http://www.shef.ac.uk

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