ScientificAmerican.com: Consciousness-Raising: Kick-Starting the Brain's Dopamine System May Revive Some Vegetative Patients

By Jesse Emspak

A clinical trial seeks to determine if apomorphine, once used to treat Parkinson's symptoms, could speed recovery from certain kinds of brain trauma

Esteban Fridman of the FLENI hospital in Buenos Aires thinks the crux of the problem for such patients lies in their neuron-connecting axons. They are so badly damaged that they have a difficult time carrying chemical signals, or neurotransmitters, from neuron to neuron. Axons get disrupted when they are subject to stresses such as cranial impact—as when a fighter gets hit in the head or a driver smacks into the steering wheel in a car accident.

As a possible treatment for such damage, Fridman has focused on apomorphine, which binds to the brain's dopamine receptors. Dopamine, a neurotransmitter well known for its role in Parkinson's disease, is part of the mechanism controlling arousal and motivated behavior; it also plays a role in consciousness disorders.

Fridman first tried apomorphine on a patient in 2004. The man had been in a minimally conscious state for 104 days. After he was given the drug the patient's mother called Fridman to tell him her son had awakened after only 24 hours.

Over the next few years, Fridman and a colleague, Ben Zion Krimchansky at the Loewenstein Hospital Rehabilitation Center in Israel tried the drug on a total of eight patients. Seven recovered consciousness. (One subsequently died of an unrelated problem.) One welcome effect, Fridman says, was that patients did not regress even after the treatment was discontinued. Five improved to where they could walk, and one can now drive by himself. Fridman published some of these results in Neurotherapeutics in 2007 as well as one of his single patient observations in Brain Injury in 2009.

But because these clinical observations were not double-blind studies—in which neither the physicians nor the patients know if subjects get a placebo or the drug—Fridman currently is starting a formal clinical study with a total of 76 patients. The apomorphine will be given between one and four months after a traumatic brain injury, and the dosages will be spread over several weeks, given over 12-hour periods. Some patients will get the drug and some will be controls.

The study is being sponsored by Boston-based Neurohealing Pharmaceuticals with initial funding from a U.S. Food and Drug Administration "orphan drug" (a pharmaceutical developed for a rare condition) grant. It is scheduled for completion later this year, although it will more likely be finished in 2011, according to Neurohealing president Daniel Katzman.