BioWorld International Correspondent
LONDON - Oxford BioMedica plc received approval to start a Phase I/II trial of its ProSavin treatment for Parkinson's disease, making it the first gene therapy for that condition to be tested in Europe, and the first use in humans of the company's lentiviral vector.
The trial, in 18 patients, will take place at the Henri Mondor Hospital in Paris.
ProSavin uses the lentiviral vector to deliver genes for the three enzymes - tyrosine hydroxylase, GTP-cyclohyrolase 1 and aromatic amino acid decarboxylase - that are required for the synthesis of the neurotransmitter dopamine. The product is administered by microinjection into the striatum, where it works to convert the target cells into a replacement dopamine factory.
The French regulatory bodies had been very positive, and it was not too difficult to get approval for the trial, Andrew Wood, chief financial officer of the Oxford, UK-based company, told BioWorld International. "We had good support from the ethical committee, and they signed the protocol off early," he said. It also helped that there are other gene therapy treatments in development for Parkinson's disease in the U.S., though using different vectors, and that there is proof of principle for replacing dopamine using fetal cell implants.
It is thought unlikely that ProSavin will result in excessive production of dopamine, a complication of some other treatments. Wood said that in animal models there is restoration of function at 15 percent to 20 percent of normal levels of dopamine production, so there is room to overshoot the effective level, while still staying below normal production levels.
The administration of ProSavin involves a procedure similar in length to deep-brain stimulation used to treat Parkinson's. The primary objectives of the trial are to assess safety and efficacy.
The study will enroll patients who have been diagnosed with Parkinson's disease and are failing L-dopa therapy, but who have not progressed to drug-induced dyskinesias. The first three patients will receive what is thought to be the lowest effective dose, while a second group of three patients will be given what is thought to be the optimal dose. Of the remaining 12 patients, four will be given sham surgery.
"This is important because of the high level of placebo effect in dopamine replacement," Wood said. "Anticipating success can cause dopamine release."
There will be a month-long gap between treating each patient, which Wood said is "paramount to make sure there is no toxicity."
In animal tests with macaque monkeys, there have been statistically significant improvements within two weeks of treatment that continue for up to six to eight weeks. The longest treated macaque remains fully fit after 27 months.
"We've been amazed by the quality of the animal data. The macaques - a very predictive model for humans - are, to all intents, cured," Wood said.
The animal studies were carried out by Stephane Palfi, the neurosurgeon who will perform the human trial. The primary endpoint will be an assessment after six months using the Parkinson's disease rating score. The secondary endpoint will be the extent to which L-dopa therapy can be reduced.
First results are expected in the second quarter of 2008.