Tuesday March 18 2008
CEA
Parkinson's disease: steps toward new potential treatments using gene therapy
CEA
Teams from MIRCen, working in partnership with Oxford Biomedica, Paris 12 university and Paris Mondor Hospital, are launching Europe’s first* set of clinical gene therapy trials on Parkinson’s disease.
Parkinson’s disease is characterised by motor disorders, a decrease in spontaneous movement, balance disorder, muscle rigidity and tremor, culminating in major invalidity 10 to 15 years following onset.
The fundamental lesion involved is the degeneration of a certain type of neurons, called dopaminergic neurons. These neurons produce dopamine, which is one of the brain’s neurotransmitters. In particular, the degenerative process affects the neurons responsible for motor skills. While patients generally follow a treatment based on L-dopa, a drug that increases the quantity of dopamine in the brain, L-dopa therapy remains problematic in that it triggers serious side effects, including the emergence of motor fluctuations that set in after the first few years of treatment. This is why hope is now turned to gene therapy.
The current challenge for antiparkinsonian therapy is to develop a technology able to give continuous local dopaminergic stimulation inducing the clinically beneficial effects without triggering the motor and neuropsychological complications associated with L-dopa therapy.
Gene transfer is currently the best-geared approach for the continuous administration of proteins to a specific site in the central nervous system. The gene therapy technique employed under this pioneering programme involves transferring genes for the enzymes required for dopamine biosynthesis into the cells of the striatum. The viral transfer of three genes into the striatum of parkinsonian patients is designed to trigger local and continuous production of dopamine in vivo, making it possible to correct the motor symptoms involved in the disease without causing the debilitating drug-induced motor complications.
Once the teams involved in the programme had established the feasibility of the gene transfer therapy and demonstrated its short- and long-term (up to 24 months) therapeutic efficacy in a primate model of Parkinson's disease, they were granted authorisation from the French Health Products Safety Agency (AFSSAPS) to initiate biomedical trials (phase I/II) at Henri Mondor Hospital. This pioneering new move should allow the teams to demonstrate the safety and efficacy of the approach in patients presenting advanced forms of Parkinson's disease.
* and the world's first for this type of delivery vector.