PALFI Stéphane
Mircen Fontenay aux Roses
France
Dopamine Gene therapy for the treatment of Motor and Non-motor symptoms of Parkinson disease. A translational program from Non-Human primate models to patients
ANR
608,350
01/02/2014
4.0
Parkinson's disease & PD-related disorders
Parkinsons Disease (PD) is a progressive disorder, commonly characterised by a loss of pigmented neurons within the substantia nigra pars compacta that send axonal projection to the striatum, and in particular the caudate and putamen, resulting in decreased dopamine availability. Clinically, PD is a multisymptomatic neurological disease that includes not only motor symptoms (akinesia, rigidity, tremor) but also non-motor symptoms (psychiatric symptoms such as depression, hypomania and visual hallucinations; cognitive and neuropsychiatric symptoms).
Currently, there is no curative treatment to halt disease progression for PD patients. Therapies include both pharmacologic and surgical approaches but display severe adverse events. Among those, L-DOPA (the metabolic precursor to dopamine) is the most effective symptomatic therapy available and the most commonly prescribed drug for the condition. However, it leads to increase motor fluctuations and dyskinesias.
ProSavin® is a gene therapy approach for PD, which delivers genes encoding the three key enzymes of dopamine biosynthesis pathway to allow long term dopamine replacement in the striatum. Given very encouraging indications of therapeutic benefit for the PD patients combined with an excellent safety profile, evaluation of a higher dose level of ProSavin® would be advantageous before progressing to a randomized sham controlled Phase II study. However, increasing the volume injected per hemisphere is undesirable. A new therapeutic vector (OXB 102), yielding greater levels of dopamine than ProSavin®, has thus been generated. It is currently under investigation in PD primates and shows very encouraging preliminary results with up to 80% motor recovery.