Navigation Links
Novel drug wipes out deadliest malaria parasite through starvation
Date:12/7/2011

December 7, 2011(BRONX, NY)An antimalarial agent developed by researchers at Albert Einstein College of Medicine of Yeshiva University proved effective at clearing infections caused by the malaria parasite most lethal to humans by literally starving the parasites to death. The novel research, carried out on a small number of non-human primates, could bolster efforts to develop more potent therapies against one of the world's leading killers. The study, published in the November 11, 2011 issue of PLoS ONE, was led by senior author Vern Schramm, Ph.D., professor and Ruth Merns Chair in Biochemistry at Einstein.

Malaria is a mosquito-borne disease caused by single-celled parasites belonging to the Plasmodium genus. The U.S. Centers for Disease Control and Prevention estimated that in 2008 (the latest year for which figures are available) between 190 million and 311 million cases of malaria occurred worldwide and between 708,000 and 1.003 million people died, most of them young children in sub-Saharan Africa. Plasmodium falciparum, the malaria species most likely to cause severe infections and death, is very common in many countries in Africa south of the Sahara desert.

The Einstein researchers exploited what is arguably P. falciparum's Achilles' heel: it can't synthesize purines, vital building blocks for making DNA. Instead, the parasite must make purines indirectly, by using an enzyme called purine nucleoside phosphorylase (PNP) to make a purine precursor called hypoxanthine. By inhibiting PNP, the drug BCX4945 kills the parasites by starving them of the purines they need to survive.

After BCX4945 showed potency against laboratory cultures of P. falciparum, owl monkeys were chosen as the non-human primate model for further testing of the drug. Three animals were infected with a strain of P. falciparum that is consistently lethal without antimalarial therapy. Orally administering BCX4945 twice a day for seven days cleared the infections from all the animals between the fourth and seventh day of treatment. The monkeys remained parasite-negative for up to nine days post-treatment. Parasitic infection eventually returned in all three monkeys after treatment ended, although a lower rate of parasitic growth was observed. No signs of toxicity were observed during the study period (30 days after the first dose).

BCX4945 belongs to a class of drugs known as transition state analogs that Dr. Schramm has been developing since 1994. Transition states form in every chemical change and whenever an enzyme does its job of converting one chemical (the substrate) into another (the product). The fleeting transition-state molecule is neither substrate nor product, but something in betweena ghostly intermediate to which the enzyme clings for just one billionth of a millionth of a second.

After figuring out the brief-lived transition-state structure for a particular enzyme, Dr. Schramm is able to design transition-state analogs to knock that enzyme out of action. The analogs closely resemble the actual transition-state structure but with one big difference: they powerfully inhibit the enzyme by binding to it and not letting go.

The transition-state analog BCX4945 was chosen for this study because of its high affinity for both P. falciparum PNP and human PNP (which the parasite obtains from the red blood cells it infects). Since PNP is abundant in mammalian red blood cells and those cells are constantly replaced, BCX4945 is toxic only to the parasite and not its mammalian hosts. (Two of Dr. Schramm's other PNP inhibitorsone for T-cell cancers, the other for goutare being evaluated in clinical trials.)

"Inhibiting PNP differs from all other current approaches for treating malaria," said Dr. Schramm. "For that reason, BCX4945 fits well with the current World Health Organization protocols for malaria treatment, which call for using combination-therapy approaches against the disease."


'/>"/>

Contact: Kim Newman
sciencenews@einstein.yu.edu
718-430-3101
Albert Einstein College of Medicine
Source:Eurekalert

Related medicine news :

1. Novel approach to treating breast cancer shows great promise
2. Wayne State receives $1.9 million from NIH to create novel cystic fibrosis treatments
3. Novel ALS drug slows symptom progression, reduces mortality in phase 2 trial
4. Wayne State University to study novel treatment for antibiotic-resistant bacteria
5. Novel, noninvasive measurement a strong predictor for heart failure in general population
6. UK HealthCare surgeons are first to perform novel procedures prior to transplant
7. Novel approach to treat proliferative vitreoretinopathy shows promise
8. Novel strategy stymies SARS et al.
9. Novel therapeutic target identified to decrease triglycerides and increase good cholesterol
10. Innovation at Regenstrief: Leveraging novel ideas to improve health care
11. Novel technique reveals both gene number and protein expression simultaneously
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... Lake Orion, Clarkston, Michigan (PRWEB) , ... June ... ... direction with respect to fertility once they have been diagnosed with endometriosis. These ... tolerable intercourse but they also require a comprehensive approach that can help for ...
(Date:6/25/2016)... FL (PRWEB) , ... June 25, 2016 , ... The temporary closing of Bruton Memorial ... Plant City Observer , brings up a new, often overlooked aspect of head lice: the ... closing for fumigation is not a common occurrence, but a necessary one in the event ...
(Date:6/25/2016)... ... June 25, 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe ... from the David Geffen School of Medicine at UCLA. He trained in Internal Medicine ... his fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the ...
(Date:6/25/2016)... Montreal, Canada (PRWEB) , ... June 25, 2016 , ... ... the pursuit of success. In terms of the latter, setting the bar too high ... low, risk more than just slow progress toward their goal. , Research from ...
(Date:6/24/2016)... ... 2016 , ... June 19, 2016 is World Sickle Cell Observance Day. In ... benefits of holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued ... Sickle Cell Disease (SCD) is a disorder of the red blood cells, which can ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... June 23, 2016 Roche (SIX: RO, ROG; ... for its Elecsys BRAHMS PCT (procalcitonin) assay as a ... septic shock. With this clearance, Roche is the first ... integrated solution for sepsis risk assessment and management. ... infection and PCT levels in blood can aid clinicians ...
(Date:6/23/2016)... Capricor Therapeutics, Inc. ... company focused on the discovery, development and commercialization ... in its ongoing randomized HOPE-Duchenne clinical trial (Halt ... its 24-patient target. Capricor expects the trial to ... 2016, and to report top line data from ...
(Date:6/23/2016)... -- Bracket , a leading clinical trial technology and ... platform, Bracket eCOA (SM) 6.0, at the 52 nd ... 2016 in Philadelphia , Pennsylvania.  A demonstration ... of its kind to fully integrate with RTSM, will be ... is a flexible platform for electronic clinical outcomes assessments that ...
Breaking Medicine Technology: