The gene therapy was used on eight patients with early-stage Alzheimer's and it was found that six successfully received the gene transfer and had a slower rate of cognitive decline in the 22 months after treatment than in the 14 months before, as measured by a standardized test.

Gene therapy has been tried for 15 years for a variety of diseases, with little success and in many cases, hints of efficacy in early trials like this one were not confirmed in larger studies where treatment was compared with a placebo.

The gene involved in this trial controls production of nerve growth factor, a protein that can protect brain cells from death. Previous attempts to use the growth factor itself as a drug have had severe side effects.

In the trial the first two patients, sedated but awake, moved their heads during the surgery and suffered brain haemorrhages, with one of them eventually dying. In the next six operations general anaesthesia was used and they were successful.

Dr. Tuszynski and colleagues from University of California, San Diego thought that it might be better to use the gene to induce cells in the brain to produce their own growth factor just where it was needed. They took skin cells from each patient's back and, in the laboratory, used a virus to carry the gene into the cells. The cells, which began producing the growth factor, were then injected into the brain.

A paper on the trial was published online yesterday in Nature Medicine.

The researchers plan further experiments to evaluate the therapeutic effects of BH4 in hypertrophy and how it, together with NOS3, compensates for the damage that leads to heart failure.

Funding for the two-year study came from the National Institutes of Health (NIH), the American Heart Association, the Peter Belfer Laboratory Foundation, the American Physiological Society and the Bernard Family Foundation.

The lead Hopkins researchers who took part in this study were Eiki Takimoto, M.D., Ph.D.; Hunter Champion, M.D., Ph.D.; and Maxiang Li, M.D., Ph.D. Other Hopkins researchers who took part were Shuxun Ren, M.D.; E. Rene Rodriguez, M.D.; Nazareno Paolocci, Ph.D.; Kathleen Gabrielson, D.V.M., Ph.D.; and Yibin Wang, Ph.D. Other researchers included Barbara Tavazzi, Ph.D., University of Rome, Italy; and Giuseppe Lazzarino, Ph.D., University of Catania, Italy. Senior study author Kass is also the Abraham and Virginia Weiss Professor of Cardiology at Hopkins.

Research to date is limited on BH4, but the cofactor is being used as a treatment for phenylketonuria, a rare genetic disorder in children that results from a deficiency in the enzyme phenylalanine hydroxylase. Loss of this enzyme can lead to mental retardation, organ damage and unusual posture.

Cardiac hypertrophy commonly develops from high blood pressure, which forces the heart to pump harder to circulate blood throughout the body. According to the latest statistics from the American Heart Association, in 2002, 65 million Americans have high blood pressure (defined as systolic pressure of 140 millimeters of mercury or greater, and/or a diastolic pressure of 90 millimeters of mercury or greater, taking antihypertensive medication or being told at least twice by a physician or other health professional that they have high blood pressure). Patients who develop hypertrophy have two to three times the risk of suffering cardiovascular disease, including heart failure and sudden cardiac death.

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