Gene Therapy May Replace Depression Medication

Researchers at the New York-Presbyterian Hospital/Weill Cornell Medical Centre have identified a gene that plays a key role in major depression.  The researchers studied the activity of the P11 gene in a small part of the brain that is the center for reward and pleasure. This part of the brain is significant in depression because depression sufferers lose the inability to enjoy and gain satisfaction from normally pleasurable activities in life (called anhedonia).

The researchers discovered that P11 is needed to bring receptors for the neurotransmitter serotonin to the surface of nerve cells to allow the brain chemical to bind to them. One of serotonin's key functions is to regulate mood, and most modern depression medication works by regulating levels of serotonin in the brain. "We potentially have a novel therapy to target what we now believe is one root cause of human depression," said a member of the research team, Dr. Michael Kaplitt.  Kaplitt is an associate professor and vice chairman for research of neurological surgery at WeillCornellMedicalCollege and a neurosurgeon at New York-Presbyterian Hospital/Weill Cornell Medical Centre.

Gene therapy is a technique for correcting or replacing defective or missing genes to treat disease.  In most gene therapy, a "normal" gene is inserted into the patient's body to replace a faulty disease-causing one.  Although the technology is still considered experimental, it is showing promise in a great many areas, including treating cancer, cystic fibrosis and blindness. The same team of scientists has been testing a gene therapy technique in the brains of Parkinson's disease patients, which they could say could easily be adapted to treat depression.

When the scientists disabled the P11 gene in mice, the mice showed symptoms of depression.  But when they inserted an active P11 gene, the depressed behaviors were reversed.  They also studied the brains of deceased depression patients and non-depressed people, and found significantly lower levels of P11 in the brains of the depressed patients. The team is now collaborating with a team from the National Institute of Mental Health to conduct further studies on monkeys. Interestingly, Kaplitt has already formed a company and licensed the intellectual property rights to the p11 gene therapy for behavioral disorders.

Depression is so prevalent in North America that it is sometimes referred to as "the common cold" of mental illness. Over 13 million American adults are diagnosed with depression each year, and almost 27 million Americans are taking antidepressant drugs, with around 165 million prescriptions written annually. The antidepressant medications Wellbutrin (and Wellbutrin XL) and Effexor (and Effexor XR) are two of the top-selling prescription medications in the world.

The social and economic impacts of depression of13 million depressed Americians are staggering. Untreated depression leads to suicide in about 15% of cases. The direct and indirect costs of depression including healthcare costs, prescription antidepressant medication, lost time from work and lost productivity are estimated to be over $30 billion a year. While the research team believes that depression is a complex disorder that probably involves a number of brain functions and circuits, they are hopeful their discovery will open the door to the possibility of using gene therapy to combat the illness.