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:12/8/2016)... ... December 08, 2016 , ... Russ DiGilio ... the first national #QuackGivesBack campaign which supported local breast cancer organizations during National ... Quack Gives Back initiative, and we’re very pleased with the participation ...
(Date:12/8/2016)... ... December 08, 2016 , ... With the increasing demand for dental ... Your Mouth?” (WIYM) campaign to inform dentists and patients about the safety issues related ... and prosthetic market in the U.S. is projected to reach $6.4 billion in 2018 ...
(Date:12/8/2016)... ... December 08, 2016 , ... Catalent Pharma Solutions, ... biologics and consumer health products, today announced that it had joined the Pharmaceutical ... a non-profit organization to unite pharmaceutical and healthcare companies that share a vision ...
(Date:12/8/2016)... ... December 08, 2016 , ... ... Care Act. Dr. Botelho advocates for the mass media launching of story movements ... ongoing opportunities to share their unfortunate experiences; such a movement can generate the ...
(Date:12/8/2016)... ... December 08, 2016 , ... Peter Zipp Insurance, an ... around the greater Phoenix metropolitan region, is announcing a charity event to provide ... the Homeless Youth Connection is to promote community awareness of the ongoing needs ...
Breaking Medicine News(10 mins):
(Date:12/8/2016)... 8, 2016 Research and Markets has announced ... their offering. ... The global chromatography market to grow at a ... Market 2016-2020, has been prepared based on an in-depth market analysis with ... growth prospects over the coming years. The report also includes a discussion ...
(Date:12/8/2016)... , December 8, 2016 ... "Sugar-Based Excipients Market by Product (Actual Sugars, Sugar ... (Filler & Diluent, Tonicity Agents), Formulation (Oral, Topical, ... MarketsandMarkets, the market has witnessed healthy growth during ... at a CAGR of 4.3% between 2016 and ...
(Date:12/8/2016)... , Dec. 8, 2016  Agenovir Corporation, a ... novel antiviral therapeutics, today announced that it appointed ... officer and a member of the board of ... executive with a deep background in both founding ... founder of Agenovir, co-president of Chan Zuckerberg  Biohub ...
Breaking Medicine Technology: