A gene-based therapy for Parkinson's disease has shown positive results in improving the quality of life of patients with the most common form of the disease.

AAV-GAD is a gene-therapy in early clinical development that aims to increase production of the signaling molecule GABA, which is crucial in regulating brain activity. The one-time therapy uses an adeno-associated virus vector to deliver the GAD gene directly into the subthalamic nucleus of the midbrain, which plays a role in controlling movement and is affected in people with Parkinson's disease. The GAD gene is required for the production of GABA.

'We are excited about these impressive clinical data in Parkinson's disease,' said Dr Alexandria Forbes, president and chief executive officer of MeiraGTx, the company that developed the therapy. '...we have demonstrated that AAV-GAD is safe at all doses studied, including a higher dose than previously tested.'

Parkinson's disease is the second largest neurodegenerative condition in the world today, which affects one in 37 people in the UK. People with Parkinson's disease show a loss of another signaling molecule, dopamine, which has a role in controlling movement and motor function. There is currently no cure for Parkinson's disease, but treatments like levodopa temporarily replace dopamine levels in the brain, but the improvements are short lived.

This phase 1/2 clinical trial enrolled 14 patients with idiopathic Parkinson's disease, meaning their condition has no clear cause, and is not related to known genetic mutations that cause around 15 percent of cases. All patients had shown a response to levodopa treatment for at least 12 months and had a moderate level of motor symptoms while not taking medication. The 14 subjects were randomly divided into three groups; five patients were treated with a high dose of the AAV-GAD gene therapy, five with a low dose and four had a sham, or placebo, procedure. The primary objective of the trial was to assess the safety and tolerability of the therapy after six months.

No serious adverse effects related to AAV-GAD therapy were reported. The high dose and low-dose groups reported improvements in quality of life from a 39-question survey of quality of life. High-dose patients improved by an average of eight points from baseline, and low-dose patients six points. No improvements were noted from the patients who received the sham procedure. Furthermore, an 18 point improvement in motor function was observed in the high-dose group.

'These safety and outcome results are excellent. The extent of motor score improvements in patients who received the high dose treatment combined with significant quality of life improvement measures are very encouraging for both patients and physicians', said Dr Ali Rezai, executive chair of the Rockefeller Neuroscience Institute at West Virginia University and principal investigator of the AAV-GAD study.

Patients who completed this trial now have the option to enroll in a longer-term follow up, and MeiraGTx is in discussion with US, European and Japanese regulators regarding the phase 3 development of AAV-GAD gene therapy.

'We have now treated a total of 58 patients... in three independent multicentre clinical studies and have seen no [serious adverse effects] related to AAV-GAD treatment,' explained Dr Forbes.