P2.205 A phase I/II clinical trial to evaluate the safety and efflcacy of ProSavin®, a gene therapy approach for Parkinson's disease

Jarraya, Béchir; Lepetit, H.; Ralph, Scott; Boulet, Sabrina; Jan, C.; Bonvento, Gilles; Miskin, James; Gurruchaga, Jean‐Marc; Vinti, M.; Fénelon, Gilles; Brugière, Pierre; Kingsman, Susan M.; Hantraye, Philippe; Rémy, Philippe; Mitrophanous, Kyriacos; Palfl, S.

doi:10.1016/s1353-8020(09)70556-5

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“…Engineering TH and GTPCH instead of AADC alone could help to improve the endogenous DA system. Such an attempt has already been made in vitro [231], in animal models [232] and is now also part of a phase I study [233]. An alternative gene therapy approach could be the use of engineered and more active TH versions, providing increased tyrosine hydroxylation rates and higher stability towards oxidative stress.…”

Section: From the Lab To Clinical Applicationmentioning

confidence: 99%

Complexity of dopamine metabolism

2013

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Parkinson’s disease (PD) coincides with a dramatic loss of dopaminergic neurons within the substantia nigra. A key player in the loss of dopaminergic neurons is oxidative stress. Dopamine (DA) metabolism itself is strongly linked to oxidative stress as its degradation generates reactive oxygen species (ROS) and DA oxidation can lead to endogenous neurotoxins whereas some DA derivatives show antioxidative effects. Therefore, DA metabolism is of special importance for neuronal redox-homeostasis and viability.In this review we highlight different aspects of dopamine metabolism in the context of PD and neurodegeneration. Since most reviews focus only on single aspects of the DA system, we will give a broader overview by looking at DA biosynthesis, sequestration, degradation and oxidation chemistry at the metabolic level, as well as at the transcriptional, translational and posttranslational regulation of all enzymes involved. This is followed by a short overview of cellular models currently used in PD research. Finally, we will address the topic from a medical point of view which directly aims to encounter PD.

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Section: From the Lab To Clinical Applicationmentioning

confidence: 99%