Med Check

According to the National Institutes of Health (NIH), as many as 3,000 genes express proteins whose molecular actions could be altered by medicines, yet only 10 percent of these “druggable genes” are targeted by drugs that have been approved by the Food and Drug Administration (FDA).

The NIH recently announced the launch of Illuminating the Druggable Genome (IDG), a three-year pilot project to explore poorly understood genes that have the potential to be modified by medicines. The IDG will target understudied genes of four important protein families that may be affected by medications—nuclear receptors, ion channels, protein kinases, and G-protein coupled receptors.

“We have a gap in the drug-development pipeline between what gene activities we know could be modified by medication and what currently is targeted,” said James Anderson, M.D., Ph.D., director of the NIH Division of Program Coordination, Planning, and Strategic Initiatives. “By focusing on understudied genes, we hope to find potential targets for medications to treat or cure some of our most burdensome diseases—and then share what we learn so that all can build on this knowledge.”

Primary funding for pilot awards is coming from the NIH Common Fund, which supports high-impact pioneering research in all divisions of NIH. Institutions granted awards will thoroughly investigate potential gene targets and share what they learn on a public resource that will help the larger scientific community build on the findings through basic research and clinical translation.

In late August, Alkermes submitted a New Drug Application (NDA) to the FDA for approval of aripiprazole lauroxil, a once-monthly, long-acting, injectable atypical antipsychotic intended for schizophrenia treatment.

The data submitted as part of this NDA include positive results from a phase 3 study testing the efficacy and safety of aripiprazole lauroxil, in which the drug was associated with significant improvements in schizophrenia symptoms, compared with placebo (Psychiatric News, June 4).

Regarding the NDA, Richard Pops, CEO of Alkermes, said the clinical trial data “position aripiprazole lauroxil to be a meaningful new entrant in the growing, long-acting injectable antipsychotic market, and we look forward to working with the FDA to bring this important new medication to patients and physicians as quickly as possible.”

Novartis recently announced that it will partner with the Banner Alzheimer’s Institute, an arm of Banner Health, to test whether two antiamyloid drugs developed by Novartis can prevent the onset of Alzheimer’s disease (AD) in people who carry genetic mutations associated with the neurocognitive disorder.

“There is a huge unmet need for treatments that prevent or delay the development of the disease,” said David Epstein, B.Sc., M.B.A, a division head of Novartis. “We are excited about taking research in Alzheimer’s to the next level.”

The two drugs to be tested are CAD106, an injectable immunotherapy in phase 2 development that triggers the production of natural antibodies against amyloid proteins, and BACE inhibitor, an oral medication in phase 1 development that prevents the production of amyloid.

The medications will be compared with placebo in 1,300 people aged 60 to 75 who do not have the cognitive disorder, but who carry two copies of the APO4 allele, a genetic risk factor for the onset of AD. If regulatory approval is given, Novartis plans to initiate studies in North America and Europe in 2015.

Many clinical trials of new medications targeting amyloid-beta and tau proteins have failed to show that the product reduces symptoms associated with AD. But a recent study suggests that a new molecule may serve as a potential target to help drugmakers achieve success in developing medications to fight neurocognitive decline.

Researchers from the Blantchett Rockefeller Neuroscience Institute (BRNI) and Neurotrope Bioscience found that the levels of protein kinase C epsilon (PKC-e), a key regulator of cell function, were significantly lower in the hippocampus and temporal lobe—areas affected by neurocognitive disorders—of people with AD, compared with healthy controls. Low levels of PKC-e in the brain were significantly correlated with an accepted measure of disease severity, known as the Braak score, which is used to classify the progression of AD. In addition, levels of amyloid-beta oligomer, a toxic protein associated with the presence of AD, were elevated in brains in which PKC-e was reduced.

“The results of this study are compelling and warrant continued research to fully explore the importance of PKC-e in the identification and treatment of patients with AD,” said Daniel Alkon, M.D., Toyota Chair in Neurodegenerative Disease at BRNI and chief scientific officer of Neurotrope. “The data compiled from this study … [provide an] incentive to pursue what could lead to a major shift in the medical community’s approach to this debilitating and costly disease.”

Currently BRNI and Neurotrope are collaborating on the development of the compound bryostatin-1, a potent modulator of PKC-e, for the treatment of patients with AD. ■