WASHINGTON, Oct. 21 (UPI) -- A new pharmaceutical that prevents bacteria from making the substances that cause disease was found in a library of small molecules produced by a commercial vendor and developed to work against cholera.
The product could be the beginning of a new class of agents to work against almost all known bacterial organisms.
The researchers, John Mekalanos, professor and chair of the Department of Microbiology and Molecular Genetics at Harvard University, and Dr. Deborah Hung, instructor in medicine at the same institution and on staff at the Division of Infectious Diseases at Brigham and Women's Hospital in Boston, have not named the new class of drug they discovered, but they call the anti-cholera compound Virstatin.
The original molecule was developed by the team to work specifically against Vibrio cholerae, the organism that causes cholera.
Instead of killing the bacteria like most antibiotics, Virstatin keeps V. cholerae from producing the toxins that cause diarrhea, effectively disarming it while it is in the body and giving the host's natural defense mechanisms time to clear the organism from the system.
"It's like trying to empty a bathtub," Hung told United Press International. "If you turn off the faucet, the water leaves faster."
Because it does not disturb their DNA, RNA or protein synthesis, bacteria cannot detect Virstatin and cannot mutate to avoid its effects. Also, because Virstatin focuses only on the mechanisms of V. cholerae, the drug does not affect or produce antibiotic resistance in other organisms, such as salmonella and shigella, which often flourish in the same conditions that produce cholera epidemics and also need to be treated.
Mekalanos and Hung tested the drug in mice and found it worked both prophylactically to prevent the disease and eradicated symptoms and shortened the disease course once cholera developed.
"That means it could be given in low maintenance doses to prevent the cholera epidemics that ravage 80 percent of refugee camps in the first two years of their existence and could also be used, perhaps in combination with other medications, to treat active disease," Mekalanos told UPI. "This could have a huge effect on world health and will also be useful against bioterrorism, since cholera is one of the diseases that can be used as a weapon because it is easily spread through food and contact with human waste."
Hung said the drug requires only one step to make, and dosages of 500 mg probably would work for an adult.
"We don't expect drug companies to beat a path to our door when we finally have a compound ready for human testing, but they will be able to recoup their costs if they sell it at a reasonable price," Mekalanos said. "It's also stable enough to be stockpiled by humanitarian organizations so it can be used when disease outbreaks occur."
Writing in the Oct. 14 issue of the journal Science, Mekalanos and Hung said Virstatin was only the first compound of its kind they had tested, and they already had isolated another that was 10 times more effective against cholera and could be delivered at even lower doses.
Mekalanos said all bacterial organisms could become targets of drugs such as Virstatin, including tuberculosis, which currently is causing worldwide concern because of its ability to mutate into antibiotic resistant forms.
Dr. Peter Katona, associate professor of clinical medicine in the Division of Infectious Diseases at UCLA Medical Center, said he found the work by Mekalanos and Hung heartening.
"We're always looking for new ways to attack bacteria," Katona told UPI. "This discovery looks very promising, but it's in an early stage of development."
He said it usually takes $500 million to $700 million to bring an antibiotic to market, and most pharma companies avoid developing such medications because they need to be taken only for a week or two, while cholesterol-lowering medications are taken for life and therefore produce much more revenue.
"Antibiotics need to be really spectacular to interest a drug company these days," Katona said, "which is why so few new ones have come out recently. I wish these investigators well. It's always a pleasure to see people trying to find new ways to fight disease. I wish more people would do it."
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Astara March covers medical research and technology for UPI. E-mail: [email protected]
