The Burrill Report


Gene therapy has shown promise recently in a range of diseases from treating inherited forms of blindness to the so-called “bubble boy” disorder SCIDs. Depression may soon be added to the list, at least if you are a mouse.

Researchers at NewYork-Presbyterian Hospital/Weill Cornell Medical Center say gene therapy may represent a new tool to treat patients with major depression when traditional drug treatments fail. The study, published in the October 20 issue of Science Translational Medicine, shows the effects of a critical protein in a specific region of the brain in mice with depression-like behaviors. They say gene therapy could be used to get depressed patients missing the protein to produce it. They hope to try the approach in a human clinical trial. A similar approach has been used in human clinical trials of patients with Parkinson's disease. Results from that 45-patient phase 2 trial are being readied for publication.

The study showed that a brain protein known as p11 in a single, small brain, area is critical to the feelings of reward and pleasure that are often missing in depression. This brain region had primarily been studied in addiction research, but the inability to find satisfaction with positive life experiences is one of the major sources of disability in depression.

The p11 protein is needed to bring receptors that bind to the neurotransmitter serotonin to the surface of nerve cells. In the brain, serotonin regulates mood, appetite and sleep, among other functions, and most antidepressants seek to regulate serotonin. In the absence of the protein, a neuron can produce all the serotonin receptors it needs, but they will not be transported to the cell surface and therefore won't latch on to the neurotransmitter.

“Given our findings, we potentially have a novel therapy to target what we now believe is one root cause of human depression,” says the study's senior investigator, Michael Kaplitt, associate professor and vice chairman for research of neurological surgery at Weill Cornell Medical College and a neurosurgeon at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. Kaplitt is a founder of and paid consultant for Neurologix, which has licensed intellectual property rights to p11 gene therapy for behavioral disorders. He is also one of the inventors on a patent application assigned to Cornell University related to p11 gene therapy for behavioral disorders.

The researchers say that not only could the gene therapy be used to restore p11, but future research may identify a small molecule to restore p11. Kapplitt says current therapies for depression treat symptoms, but not the underlying cause. He said gene therapy may provide an alternative for patients who do not respond to existing treatments.


October 21, 2010
http://www.burrillreport.com/article-reversing_depression_with_gene_therapy.html