Substances harvested from cannabis plants could soon outshine conventional antibiotics in the escalating battle against drug-resistant bacteria. The compounds, called cannabinoids, appear to be unaffected by the mechanism that superbugs like MRSA use to evade existing antibiotics. Scientists from Italy and the United Kingdom, who published their research in the Journal of Natural Products last month, say that cannabis-based creams could also be developed to treat persistent skin infections.

Cannabis has long been known to have antibacterial properties and was studied in the 1950s as a treatment for tuberculosis and other diseases. But research into using cannabis as an antibiotic has been limited by poor knowledge of the plant's active ingredients and by the controversy surrounding its use as a recreational drug.

Now Giovanni Appendino of the Piemonte Orientale University, in Italy, and Simon Gibbons of the School of Pharmacy at the University of London, U.K., have revisited the antibiotic power of marijuana by systematically testing different cannabinoids' ability to kill MRSA.

MRSA, short for methicillin-resistant Staphylococcus aureus, is a bacterium that can cause difficult-to-treat infections since it does not respond to many antibiotics. Many healthy people carry S. aureus on their skin, but problems arise when multi-drug-resistant strains infect people with weak immune systems through an open wound. In the worst cases, the bug spreads throughout the body, causing a life-threatening infection.

To make matters worse, resistance to antibiotics is rapidly increasing, and some strains are now even immune to vancomycin, a powerful antibiotic that is normally used only as a last resort when other drugs fail.

But when Appendino, Gibbons, and their colleagues applied extracts from five major cannabinoids to bacterial cultures of six strains of MRSA, they discovered that the cannabinoids were as effective at killing the bugs as vancomycin and other antibiotics.

"The cannabinoids even showed exceptional activity against the MRSA strain that makes extra amounts of the proteins that give the bugs resistance against many antibiotics," says Gibbons. These proteins, he explains, allow the bacteria to "hoover up unwanted things from inside the cell and spit them out again."

Conveniently, of the five cannabinoids tested by the researchers, the two most effective ones also happen to be nonpsychoactive, meaning that they cannot cause a high. "What this means is, we could use fiber hemp plants that have no use as recreational drugs to cheaply and easily produce potent antibiotics," says Appendino.

In an attempt to discover how the cannabinoids kill MRSA, the team manipulated several chemical groups within the compounds. Most of the changes did not affect the antibiotic activity at all, and those that did seemed to influence only how well the cannabinoid is taken up by the bacterial cells.

"Everything points towards these compounds having been evolved by the plants as antimicrobial defenses that specifically target bacterial cells," says Gibbons. "But the actual mechanism by which they kill the bugs is still a mystery. We've tested whether the cannabinoids affect common antibiotic targets like fatty acid synthesis or the [DNA-bending enzyme] DNA gyrase, but they don't. I really cannot hazard a guess how they do it, but their high potency as antibiotics suggests there must be a very specific mechanism."

Appendino and Gibbons say that cannabinoids could quickly be developed as treatments for skin infections, provided the nonpsychoactive varieties are used. "The most practical application of cannabinoids would be as topical agents to treat ulcers and wounds in a hospital environment, decreasing the burden of antibiotics," says Appendino.

Whether the cannabinoids could also be delivered in the form of an injection or in pills is less clear, the pair says, because they may be inactivated by blood serum.

Frank Bowling of the University of Manchester, who has had success treating MRSA-infected wounds with maggots, says that "any alternative treatment that removes MRSA from the wound and prevents it from spreading into the body is fantastic and preferable to using antibiotics that have strong side effects and against which resistance is already developing." He cautions, however, that the researchers still need to show that the cannabinoids are safe to use.

This is not something that Appendino is too concerned about: "The topical use of cannabis preparations has a long tradition in European medicine, and no allergies have been reported."

Mark Rogerson of GW Pharmaceuticals, a U.K.-based company that develops cannabinoid-based drugs to treat severe pain caused by multiple sclerosis and cancer, says that the discovery that cannabinoids kill MRSA "really underlines the potentially great diversity of medical applications that cannabis-based medicine can have. You can almost think of the cannabis plant as a mini pharma industry in its own right." But Rogerson says that it is unlikely that existing cannabis-based medicines could be used to treat MRSA because the exact effect will depend on the correct combination and dosage of cannabinoids.

Meanwhile, Appendino and Gibbons hope that antibacterial effectiveness could also make cannabinoids suitable preservatives for cosmetics and toiletries. "The golden standards of preservatives are parabens and chlorinated phenols," says Appendino, but these compounds do not degrade well in the environment and are strongly suspected to be hormonal modifiers. He also argues that, since all major cannabinoids are similarly effective, complete purification of a single compound isn't necessary. So semipurified cannabinoid mixtures extracted from nonpsychoactive plants could make a cheap and easy alternative to conventional preservatives.

Copyright Technology Review 2008.

Source: http://www.technologyreview.com/Biotech/21366/

A specific structural variation on chromosome 16 dramatically boosts the risk of autism, according to a study published today in the New England Journal of Medicine. The finding--one of the most significant to date--permits the development of new diagnostic tests to identify children at risk, and could ultimately point to specific biochemical pathways to target in drug development.

"This is one of the single largest [influences] and most frequent genetic causes for autism identified so far," says Bai-Lin Wu,director of the Genetics Diagnostic Laboratory at Children's Hospital Boston and one of the senior authors on the study.

Autism spectrum disorder--or autism, as it is commonly called--refers to a group of developmental disabilities with wide-ranging language, social, and behavioral symptoms. The disorder is known to have a strong genetic influence, with up to 90 percent of cases thought to have a genetic component. However, because the disorder is linked to a combination of genetic variations, each playing a minor role, identifying specific genetic triggers has been difficult. Now new microarray technologies, which allow scientists to screen a million or more genetic variations in thousands of patients, are enabling the much larger studies needed to pinpoint these triggers.

In the new paper, scientists say that they used microarrays to scour the DNA of more than 2,000 individuals with autism. They found that deletion or duplication of approximately 500 of the same DNA letters on chromosome 16 was strongly linked to autism, accounting for about one percent of cases. "While that doesn't sound like a huge number, the fact that these people carry the identical spontaneous deletion or duplication would be incredibly unlikely to happen by chance," says Mark Daly, a geneticist at Massachusetts General Hospital's (MGH) Center for Human Genetic Research, in Boston, and at the Whitehead Institute, in Cambridge, and one of the study's senior authors.

The results were independently identified by three different groups--at MGH; Children's Hospital Boston; and deCODE Genetics, in Iceland--that are studying three different populations, giving added weight to the work.

The findings build on previous reports that autism is linked to genetic deletions or duplications that arise spontaneously, rather than being passed down through generations. In almost all cases, parents of the affected people did not carry the chromosome 16 variation.

One of the most immediate clinical benefits of the research will be the development of inexpensive diagnostic tests. "Because the variation occurs so frequently, you could directly test for the presence or absence of a duplication or deletion as part of standardized genetic testing for autism," says James Gusella, a neurogeneticist at Harvard Medical School, in Boston, who participated in the research. For example, children who show developmental delays but are too young to undergo clinical autism testing could be screened for this variation, allowing parents and doctors to prescribe intervention for those who test positive. "We will be able to find at-risk children early on so that language and behavior problems can be treated much earlier," says Yiping Shen, director of research and development at Children's Hospital's Genetics Diagnostic Laboratory, who was also involved in the work.

Such testing could also predict if parents with one autistic child are at greater risk of having another; if their child's autism is linked to a spontaneous variation, they are at no greater risk than the general population. Researchers at Children's Hospital, which provides genetic testing to families, are already developing a clinical diagnostic test.

Scientists are also trying to pinpoint the specific gene or genes within this section of DNA that underlie the increased risk. Daly and his collaborators plan to sequence this region of the genome in another group of people with autism, in search of single-letter mutations that might disrupt the function of specific genes. "Genetics provides us with the only opportunity to gain insight into the biological mechanisms that underlie autism," says Daly. "We can look at individual gene discovery as a small first step in the overall path to develop treatments."

Previous studies have identified autism risk genes. However, these studies have focused on people with genetic disorders that often co-occur with autism, such as Fragile-X syndrome, complicating the role those genes play in the disorder. "Up until now, we haven't had the capacity to look at a single gene that is associated with pure autism," says Gusella.

The findings could point to additional spots in the human genome to search for autism risk genes. The variation on chromosome 16 lies within a genetic "hot spot," an area that is predisposed to undergoing structural duplications due to the architecture of the DNA, says Evan Eichler, a geneticist at the University of Washington in Seattle, who wrote an editorial accompanying the paper. "Every time we produce gametes, there's a finite probability of this region to duplicate," he says. In addition, the region has a high concentration of genes that are rapidly evolving in humans. While the significance of that finding is not yet clear, it may explain autism's status as a relatively young disease.