Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial

Anticancer Gene Transfer for Cancer Gene Therapy

“…Clinical successes the last 5 years have breathed new air in the field of gene therapy like i.e. the treatment of X-linked SCID, ADA-SCID (Cartier and Aubourg, 2010;Aiuti et al, 2002), Xadrenoleukodystrophy (Cartier et al, 2009) and Wiskott-Aldrich Syndrome (WAS) (Boztug et al, 2010;Aiuti et al, 2013) metachromatic leukodystrophy by using ex vivo gene transfer into bone marrow hematopoietic stem cells and autologous transplantation or by direct gene transfer in vivo as in the cases of Leber congenital amaurosis (Bainbridge et al, 2008;Simonelli et al, 2010) and Parkinson's disease (LeWitt et al, 2011;Palfi et al, 2013) ONCOLYTIC VIRUSES AND VECTOR SYSTEMS FOR GENE DELIVERY There are several virus families and representatives of each family that are currently engaged in the battle with cancer. Oncolytic viruses have a native capacity of cell lysis and so innate ability of killing.…”

Is Parkinson's disease the new cancer?

“…Furthermore, dopaminergic stimulation of the mesolimbic system (involved in pleasure and reward) can trigger dopamine dysregulation syndrome and impulse control disorders, manifest as, for example, stereotyped behaviour, pathological gambling, compulsive shopping, binge eating and hypersexuality. 6,7 Therefore, continuous, stable dopamine replacement, limited to the striatum, might enhance the long-term efficacy of PD treatment. 6 Against this background, a recent open-label study assessed a gene therapy (called ProSavin) that encoded three enzymes that control dopamine synthesis: tyrosine hydroxylase; cyclohydrolase 1; and amino acid decarboxylase (AADC).…”

“…6,7 Therefore, continuous, stable dopamine replacement, limited to the striatum, might enhance the long-term efficacy of PD treatment. 6 Against this background, a recent open-label study assessed a gene therapy (called ProSavin) that encoded three enzymes that control dopamine synthesis: tyrosine hydroxylase; cyclohydrolase 1; and amino acid decarboxylase (AADC). Researchers bilaterally injected one of three doses of ProSavin into the putamen of 15 patients aged 48-65 years with advanced PD who no longer responded well to other treatments.…”

“…Nevertheless, ProSavin's effects were within the placebo range in clinical trials assessing surgery for PD, and further studies are needed. 6 In experimental studies, gene therapies that express growth factors -such as glial cell line derived neurotrophic factor (GDNF) and neurturin -enhance sur vival of dopaminergic neurons, promote neurite outgrowth and seem to increase the supply of dopamine to the striatum. Indeed, administered early in PD's natural history, growth factor gene therapies might modify the condition's course by augmenting the remaining nigrostriatal projections.…”

Gene Therapy for Parkinson’s Disease: Still a Hot Topic?

“…Preclinical studies in rodents and monkeys delivering lenti-dopamine demonstrated significant antiparkinsonian benefit. A Phase 1/2 clinical trial has been completed again demonstrating safety and tolerability with some measure of efficacy as determined via open-label assessments (Palfi et al, 2014). Another series of studies models gene therapy after deep brain stimulation (DBS).…”