Initial results from a clinical study suggest that a new gene-based therapy may help alleviate the debilitating symptoms of Parkinson’s disease, illuminating a potential reprieve from tremors, limb stiffness, and loss of balance for the millions of people living with the neurodegenerative disorder.

The new drug ProSavin was shown in a phase I trial to bring about significant improvements in motor function for all participants without considerable side-effects. According to its developers, the drug offers relief by targeting the so-called dopamine deficiency that spurs the development of stiffness and tremors in patients. Kyriacos Mitrophanous, head of research at Oxford BioMedica and senior author of an accompanying study, wrote in an email to Medical Daily that the drug is the first of its kind.

“This is the first gene therapy approach that delivers the three key enzymes in one vector required to convert cells in the brain to manufacture dopamine, the neurotransmitter that is depleted in Parkinson’s disease,” he explained. “The long-lasting benefits we have seen to date give us great hope for this product and the underlying technology.”

The trial tested basic qualities like safety, tolerability, and efficacy in a group of 15 people who had been living with Parkinson’s disease for at least five years. The participants, who were all between 48 and 65 years of age, were rated on the Unified Parkinson’s Disease Rating Scale (UPDRS) — a model that allows doctors to score difficulties in speech, tremors, rigidity, finger taps, posture, and gait in patients. Each participant then received one of three different doses of ProSavin.

Lead investigator Stéphane Palfi and his colleagues found that all 15 participants displayed improvements in these scores after they received the drug. The observed side-effects were only mild to moderate, with the most common adverse reaction being dyskinesia, or fragmented movement. As the benefits far outweigh these possible consequences, the authors are confident that the drug represents a significant step forward for Parkinson’s research.

“[A] therapeutic approach that provides continuous and stable dopamine replacement, restricted to the dopamine-depleted striatum, might provide an effective long-term treatment without the onset of behavioural complications,” they concluded.

Treating Parkinson’s Disease

Parksinson’s disease is a progressive and incurable disorder characterized by neurodegeneration — a harrowing syndrome whereby nerve connections in the brain begin to decay. With time, this process results in a range of motor impairments, including stiffness, instability, and the signature tremors. While palliative therapies are available, few offer lasting relief, as they appear to induce taxing side-effects after a certain period of use.

In this sense, ProSavin stands out, as it was not associated with any serious adverse effects after 12 months. Of the 54 drug-related side-effects reported, 51 were mild and three were moderate. If a large-scale phase II trial proves equally successful, physicians around the world could soon find themselves with a new weapon against the chronic disorder.

Still, some experts question the developers’ decision to target motor symptoms rather than non-motor symptoms like mood disorders, sleep disturbances, and slowed thinking. Dr. Jon Stoessl, a professor of neurology at the University of British Columbia in Vancouver, wrote in a commentary that, despite numerous imperfections, current motor-related therapy gets the job done. “We have reasonably good treatments for the motor manifestations of Parkinson's disease in the form of levodopa, infusion therapies, and deep brain stimulation,” he explained. “The challenge of Parkinson's disease is the management of nonmotor problems, many of which have a non-dopamine basis.”

 

Source: Palfi S, Gurruchaga MJ, Ralph S, Mitrophanous KA. et al. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson’s disease: a dose escalation, open-label, phase 1/2 trial. The Lancet. 2014.