drug discovery

Drug development: The treasure chest

Pharmaceutical research into the chemicals found in cannabis has so far supplied only one licensed medicine. But scientists think there could be hundreds more.

The annual meeting of the International Cannabinoid Research Society (ICRS) is a highly unusual scientific conference. It has been closed to all media since its inception 25 years ago, lending an air of mystery to the gathering of researchers who study the unique chemicals found in cannabis.

In a relaxation of the organization’s long-standing policy, ICRS permitted Nature reporters to attend this year’s conference, which was hosted by Acadia University in the tiny Canadian town of Wolfville, Nova Scotia. The tight-knit group of researchers are bound together by onerous government restrictions on their subject, and by their sufferance of lingering suspicions from other scientists that they are a bunch of hippies trying to get an illicit drug legalized.

“The status of cannabis as an illegal substance makes it difficult for some people to take it seriously,” concedes Mark Ware, a pain specialist at McGill University in Montreal, Canada, who focuses on the analgesic properties of cannabis. Read more in Nature.

Outlook: Addiction

Addiction is a chronic disease that can destroy the lives of individuals and their families. Researchers are teasing apart the complex neural, genetic and behavioural factors that drive people to lose the ability to resist damaging substances, and are looking for ways to treat, reverse or even prevent addictions. Read more in this special Outlook supplement I edited for Nature.

Zinc-finger nucleases make the cut in HIV

Sangamo’s lead zinc-finger therapeutic supports the potential of gene-editing technology, but CRISPR-based gene-editing therapeutics are close behind.

On 6 March, Sangamo BioSciences released the latest encouraging results for its potential anti-HIV therapy SB-728-T, a zinc-finger nuclease (ZFN) gene-editing drug. Phase I and II trials showed continued signs of safety and efficacy, it reported in the New England Journal of Medicine (N. Engl. J. Med. 370, 901–910; 2014) and in several abstracts presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in Boston, Massachusetts, USA.

SB-728-T works by targeting the CC-chemokine receptor 5 (CCR5) gene, which encodes a cell-surface receptor that HIV uses to gain entry into CD4 T cells. CCR5 is well validated as a drug target: GlaxoSmithKline’s small-molecule CCR5 inhibitor maraviroc was approved as an anti-HIV drug in 2007, people with loss-of-function CCR5 mutations are immune to many common strains of HIV, and one person, Timothy Brown — known as the ‘Berlin patient’ — has been cured of HIV since receiving a bone marrow transplant from a CCR5-mutant donor. Sangamo’s treatment breaks new ground by taking CD4 cells from a patient, disabling CCR5 by editing the gene-coding sequence and then reintroducing the modified cells back into the patient to proliferate and replace vulnerable and infected cells. Read more in NRDD.

Kinesin inhibitor marches toward first-in-class pivotal trial

The key to treating cancer is to put a stop to the out-of-control cell growth that leads to tumor formation. One way to do this is to go after the microtubules that help coordinate this rampant cell division. Yet because microtubules function in both dividing and non-dividing cells—for example, in non-dividing neurons they’re involved in intracellular transport—drugs that target microtubules directly tend to cause nerve pain and other side effects. That’s why researchers have been on the lookout for more specific targets in the microtubule machinery—ones that are only active in rapidly growing cells during mitosis.

The kinesin spindle protein (KSP), a molecular motor that crawls along the microtubules to help the cells divide, provides one such candidate target. To date, drugs designed to block this protein (which is also known as Eg5) have failed to live up to their potential, with something of a KSP inhibitor graveyard littered with failed and abandoned products from companies including Cytokinetics, AstraZeneca, Eli Lilly and others. Read more in Nature Medicine.

Bacteria-killing dispute casts doubt on antibiotic development

Antibiotic drugs are one of the cornerstones of modern medicine, but, surprisingly, scientists still don’t understand all of the ways in which they work. So when biomedical engineer James Collins and his team at Boston University announced several years back that they had discovered a common mechanism of cell death underlying all major classes of antibiotics—and that the pathway could be used to combat resistance, an increasingly growing problem—the report generated a lot of excitement. It even spawned a new company, called EnBiotix, which aims to develop antibiotic ‘adjuvants’—agents designed to weaken the defenses of superbugs and resensitize them to existing antimicrobials.

But in recent months, several different researchers have tested Collins’s idea and found it wanting. “When you look at bacteria killed by different antibiotics, it’s hard to believe there is a common mechanism,” says Frédéric Barras, a bacterial geneticist at Aix-Marseille University in France. Read more in Nature Medicine.