First clinical trial of gene therapy for Parkinson s disease is successful

By ACSH Staff — Jan 16, 2014
A small pilot study of gene therapy for Parkinson s disease showed improvement in severe motor symptoms. There were no side effects of significance, and all three doses had beneficial effect.

Brain MRI-Alzheimer'sParkinson s disease is the second most common neurodegenerative disorder after Alzheimer s, affecting about 5 million people worldwide, including at least 50,000 new cases in the U.S. each year. The symptoms of Parkinson s are due to loss of dopamine-producing nerve cells in the part of the brain responsible for controlling movement.

The most widely used treatment is the drug levodopa, a precursor of dopamine that can cross the blood-brain barrier. However, over time, cell death is so great that effectiveness lessens and patients can develop involuntary muscle spasms (dyskinesias) and other side effects.

In the first study of its kind, a small proof-of-concept therapeutic trial, 15 patients with advanced Parkinson s disease (PD) were given an infusion of a triple-gene therapy directly into the area of the brain affected by the condition. The gene treatment was a combination of three separate genes known to code for dopamine production, dopamine being the key substance lacking among PD patients. The genes were carried to their target by an inactive viral vector. The study was published in the recent issue of The Lancet.

The patients were aged 48 to 65 years, and had had PD for at least 5 years. The study design was open-label: it was not a blinded study in which neither the subjects nor the scientists knew whether the active treatment or an inactive placebo was given all patients got gene therapy. The study authors, led by Prof S Palfi MD, based in Creteil, France, called their therapy ProSavin. The gene solution was administered in three different doses: high, medium and low concentration and patients were followed for one year after treatment.

The primary endpoints of this early trial were the number and severity of adverse events associated with ProSavin, and motor responses as assessed with a standardized evaluation protocol. The results showed no serious drug- or surgery-related adverse effects, and all patients experienced significant improvement in motor function off their usual medications at the 12 month assessment. The authors concluded that "ProSavin was safe and well tolerated in patients with advanced Parkinson's disease. Improvement in motor behaviour was observed in all patients.

An editorial by Dr. A Jon Stoessl from the University of British Columbia, Vancouver, Canada in the same issue, had this perspective: The approach taken by Palfi and colleagues is novel in that it is the first time that [viral] vectors have been successfully applied to the treatment of neurological disease in humans ¦[The success of this treatment] does not depend on survival of dopaminergic neurons, but rather assumes that neurons preserved in Parkinson s disease [after being transfected with gene-bearing viral vectors] will develop the capacity to synthesise dopamine.

A related study, even smaller, of a congenital X-linked condition causing blindness and its treatment with gene therapy, was also published in this week s The Lancet. The condition is known as choroideremia, and occurs in 1 out of 50,000 males. Night blindness begins in the teenage years and progresses to complete blindness by age 50. In this study, 6 patients got gene therapy, and all had significant improvement in visual acuity.

ACSH s Dr. Gilbert Ross commented, These two studies are highly preliminary, obviously. Yet they confirm what we already know, down deep: we are on the threshold of a new age of genetic treatments for a wide variety of conditions. These 2 examples illustrate this concept: Parkinson s disease is not a genetic disorder, but the brain cells which have failed can be stimulated to ramp up their dopamine production at the behest of added genes. The eye disease is in fact a genetic condition, and treated thusly it can be ameliorated, to a degree.

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