Parkinson’s disease is a neurodegenerative disorder arising from the gradual death of nerve cells in the brain. Parkinson’s disease is a progressive and debilitating disease affecting control of bodily movement and characterized by four principal symptoms:
- tremor of the limbs,
- rigidity of the limbs,
- bradykinesia of the limbs and body evidenced by difficulty and slowness of movement, and
- postural instability.
According to the National Parkinson Foundation, it is estimated that 60,000 new cases are diagnosed each year in the United States, joining the 1 million Americans who currently have Parkinson’s disease. While the condition usually develops after the age of 65, 15% of those diagnosed are under 50.
Physicians and patients have long recognized that this disease, or treatment complications, can cause a wide spectrum of other symptoms, including dementia, abnormal speech, sleep disturbances, swallowing problems, sexual dysfunction and depression.
Rigidity, tremor, and bradykinesia result primarily from a loss of dopamine in two regions of the brain: the substantia nigra and striatum (caudate and putamen). Dopamine is a neurotransmitter, a chemical released from nerve cells (neurons), which helps regulate the flow of impulses from the substantia nigra to neurons in the caudate and putamen. Standard therapy for Parkinson’s disease often involves use of levodopa, a drug which stimulates production of dopamine. However, over extended periods of time levodopa often declines in its effectiveness. In advanced stages of Parkinson’s disease, as the disease becomes more and more debilitating, it becomes necessary to accept a riskier and potentially more invasive medical procedure to treat the disease. It is at this juncture that surgical procedures, including deep brain stimulators and lesioning, which target an area of the brain called the subthalamic nucleus (“STN”), are commonly advised.
Our Approach to Parkinson’s Disease
Neurologix believes that an inhibitory gene (glutamic acid decarbolylase or “GAD”) can be used to selectively mimic normal physiology and alter the neural circuitry affected in Parkinson’s disease. Our technology inserts the GAD gene into an AAV-based viral vector, and this packaged vector is introduced directly into the subthalamic nucleus (“STN”). The GAD gene is responsible for synthesizing gamma aminobutyric acid (“GABA”), which is released by nerve cells to inhibit or dampen activity.
The loss of dopamine leads to a change in the activity of several brain structures which control movement. Central to this is the STN, which is overactive and does not receive adequate GABA, as well as targets of the STN, which are also hyperactive and also do not receive enough GABA. The goal of our therapy is to deliver GABA to the STN in order to re-establish the normal neurochemical balance and activity among these key structures.
Our gene transfer treatment is the only non-dopamine gene therapy strategy currently in development. It is designed to reset the overactive brain cells to inhibit electrical activity and return brain network activity to more normal levels. This in turn reduces symptoms of Parkinson’s disease, including tremors, rigidity and slowness of movement. The therapy is designed to be administered without destroying brain tissue and without implanting a permanent medical device.
We published results in The Lancet and Proceedings of the National Academy of Sciences during 2007 of a Phase 1 study of its AAV/GAD therapy in patients with Advanced Parkinson’s disease – the first gene therapy study ever to be conducted for a neurodegenerative condition – demonstrating an excellent safety profile and a statistically significant improvement in clinical symptoms and brain metabolism. In December 2007, we announced that the U.S. FDA granted Fast Track Designation for our Parkinson’s treatment.
In June 2010, the Company announced positive results in its Phase 2 clinical trial of its investigational gene therapy for advanced Parkinson’s disease, NLX-P101. This trial was designed to evaluate the safety and efficacy of NLX-P101 in subjects with moderate to advanced Parkinson’s disease who were not well-controlled on available medical therapy. Approximately half of the trial participants were randomly selected to receive an infusion of the gene-based treatment bilaterally and the other half, the “Control Participants,” were randomly selected to receive a sterile saline solution.
Trial participants who received NLX-P101 experienced statistically significant and clinically meaningful improvements in off-medication motor scores compared to Control Participants who received sham surgery, measured on the Unified Parkinson’s Disease Rating Scale Part 3 (Motor section). The results also demonstrated a positive safety profile for NLX-P101, with no serious adverse events related to the gene therapy or surgical procedure reported. All treated subjects will continue to be monitored for safety for a 12-month period following their surgical procedure. Subject to the availability of adequate funds and the availability of a catheter infusion device, Control Participants who continue to meet all entry, medical and surgical criteria for the trial will be offered the opportunity to participate in the open label arm of the trial to receive a bilateral infusion of the gene-based treatment.