Biblioguide en thérapie génique
8. Parkinson et lentivecteurs
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8. Parkinson et lentiviraux. Avec quel(s) lentivirus? Avec quels résultats?

Etudiants Adriana De Pesters / Jonathan Bernard


La combinaison mots-clés/équations pertinentes en rapport avec le choix d'un outil est à revoir!

1/2 A. les mots-clés sont limités (voir suggestions en jaune). Il manque des suggestions de synonymes.

1/2 B. La grammaire des équations correspondant aux mots-clés n'est pas maîtrisée. 

1/2 C. Outils: Plusieurs outils ont été explorés, mais les équations utilisées sont rarement pertinentes, ou ne fonctionnent pas en raison d'une synthaxe fausse.

2/2 D. Les références bibliographiques sont correctes, mentionnant avec quel outil elles ont été trouvées

1/2 E. Les éléments de réponse à la question contient des affirmations référencées, mais le copié-collé est tellement long, qu'il est difficile de voir les guillemets...pour le détail, on met la citation dans un texte, juste après les guillemets, mais pas à l'intérieur. Il faudrait réduire la taille des copier-coller, pour avoir quelque chose de plus pertinent.

1/2 F. La restitution écrite de la démarche de recherche d'information est difficile à suivre. Il manque de la précision pour que le lecteur puisse reproduire vos démarches, car la rédaction est un patchwork.

Pour information, on peut utiliser des textes intégraux avec guillemets et source, ou des idées empruntées avec paraphrase et source (droit d'auteur). Mais la reproduction par copié collé d'image, de tableau, de dessin, de graphique, de statistiques, n'est pas possible, même en citant la source! Pour une reproduction, il faut demander aux auteurs et à l'éditeur la permission de reproduction (droit de diffusiont). Parfois, il faut payer pour obtenir ce droit. Autrement dit, le droit d'utilisation des "images" n'est pas le même que les idées sous forme écrite!

7 pts


Company: Oxford Biomedica
Product: ProSavin
Lentiviral vector: EIAV

ProSavin is Oxford BioMedica's gene-based therapy for Parkinson's disease that has the potential to revolutionise the treatment of this chronic neurodegenerative disorder. Using the Company's proprietary LentiVector® gene delivery technology, ProSavin delivers genes for three enzymes required for dopamine synthesis directly into the brain. Target cells are converted into a dopamine factory restoring levels of the key neurotransmitter that is depleted in patients with Parkinson's disease.ref

Parkinson's disease affects 1% of the population over 50 and about 10% of the over 60s. The estimated worldwide market is US$3 billion. None of the current treatments provide patients with long-term relief from symptoms.ref

ProSavin uses Oxford BioMedica’s proprietary LentiVector technology to deliver three genes that encode enzymes needed for dopamine synthesis (tyrosine hydroxylase, GTP-cyclohydrolase 1 and aromatic amino acid dopa decarboxylase). The product is injected directly into the brain, targeting a region called the striatum (see Figure 2). In this area, target nerve cells are transformed from cells that would not normally produce dopamine into cells that do.  This creates a new endogenous centre for dopamine synthesis, replacing the patient’s lost dopamine and relieving the symptoms of Parkinson’s disease.ref

ProSavin is currently being evaluated in a Phase I/II trial in France. Long-term efficacy data in the industry-standard preclinical model of Parkinson's disease have shown that ProSavin induces almost complete recovery from movement disorders and restores other behavioural and metabolic measurements to near normal levels.ref

In this preclinical model, the therapeutic effect of ProSavin following a single administration has been maintained for over 27 months with no diminishment. Preclinical studies demonstrated that ProSavin is safe and well tolerated, with no evidence of side-effects, even at doses that are hundreds of times higher than those to be evaluated in humans.
Ongoing Phase I/II Trial ref

    * Moderate to late-stage Parkinson's disease.
    * Eighteen patients failing on current treatment with L-DOPA, who have not progressed to drug-induced movement disorders.
    * Two-stage trial, firstly to evaluate two dose levels of ProSavin and secondly to confirm efficacy of the optimal dose.
    * Primary objectives of trial are to assess safety and efficacy of ProSavin.
    * Patient recruitment is ongoing.ref

Oxford BioMedica plans to establish a specialised neurological sales and marketing infrastructure for ProSavin in certain key territories and will seek commercial partners elsewhere.1 "




"The primary objectives of the trial are to assess the safety and efficacy of ProSavin. The analyses of patients will include the application of advanced non-invasive neuro-imaging techniques

Patients in the trial will have been diagnosed with Parkinson's disease and will be failing on current treatment with L-DOPA but they will not have progressed to drug-induced dyskinesias. It is a two-stage study. The first stage is an open-label dose escalation to evaluate two dose levels of ProSavin in cohorts of three patients each. In the second stage of the trial, a further 12 patients will be recruited to confirm efficacy of the optimal dose.

The efficacy of ProSavin will be assessed using the Unified Parkinson's Disease Rating Score (UPDRS). Patients will be monitored at regular intervals, with the primary endpoint being an efficacy assessment at six months after treatment. The secondary objective of the trial is to asses the extent to which patients' current therapy (L-DOPA) can be reduced following administration of ProSavin.2"



1. Source: Oxford Biomedica. < >. Consulté le 08.11.08

2. Source: Clinical trials Gov. < >.Consulté le 08.11.08


Note: There are several other research groups on other lentivirus to find a cure to neurodegenerative disease like PD. We can name as other vectors the HIV-1 virus or the SIN virus. Here we are not going to speak about these virus because there is no clinical trial with them for now, but you can still find some interesting references about them at the end of the page.

8.1 Mots-clés, synonymes, du plus général (domaine) au particulier

Parkinson’s disease,

gene therapy, genetic engineering, genetic therapy, drug delivery, delivery systems

lentivir*, vector

safety, toxicity, adverse effects


clinical trials,clinical applications

EIAV, Equine Infectious Anemia Virus

Oxford biomedica

8.2 Equations testées dans quel outil de recherche documentaire

Je ne comprends pas ce que sont  <..>. La grammaire comprise en recherche documentaire est AND, OR, (), "", *, ?
<Parkinson’s disease>, <lentiviral vector>, <gene therapy>, donc on pourrait écrire l'équation
"parkinson's disease" AND "lentiviral vector" AND "gene therapy"

Encyclopedia of cell technology 
<Lentivir* parkinson>

<Parkinson AND lentivir*>
<Parkinson AND oxford AND biomedica>
<lentivir* AND parkinson AND vector>
<Zufferey AND lentivir*>

<Parkinson AND lentivir*> dans le TITLE (En restreignant tout de suite à une recherche dans le titre, on a seulement 3 résultats, pourquoi pas dans tous les champs? = 54 résultats)

<Parkinson AND (lentivir* OR gene therapy) AND (clinical trials)>
<Parkinson AND EIAV AND (clinical trials)>
<Parkinson AND EIAV AND company AND (clinical trials)>
<Parkinson AND EIAV AND (oxford biomedica) AND (clinical trials)>
Google scholar 
<Parkinson AND (clinical trial) AND eiav>, on pourrait écrire Parkinson AND "clinical trial" AND (EIAV OR lentivir*)
< Parkinson AND HIV-1>

8.3 Bibliographie suggérée

Wong LF, Goodhead L, Prat C, Mitrophanous KA, Kingsman SM, Mazarakis ND.
Lentivirus-mediated gene transfer to the central nervous system: therapeutic and research applications.
Hum Gene Ther. 2006 Jan;17(1):1-9. Review. Erratum in: Hum Gene Ther. 2006 Mar;17(3):376.
PMID: 16409120 [PubMed - indexed for MEDLINE]

Azzouz M, Kingsman SM, Mazarakis ND.
Lentiviral vectors for treating and modeling human CNS disorders.
J Gene Med. 2004 Sep;6(9):951-62. Review.Dans une référence, on ne mentionne pas le type de document. Cet élément ne ait pas partie d'une référence
PMID: 15352068 [PubMed - indexed for MEDLINE]

Romano G.
Current development of lentiviral-mediated gene transfer.
Drug News Perspect. 2005 Mar;18(2):128-34. Review.
PMID: 15883621 [PubMed - indexed for MEDLINE]

Lawrence S Young *, Peter F Searle, David Onion, Vivien Mautner
Viral gene therapy strategies: from basic science to clinical application
The Journal of Pathology Early View Volume 208 Issue 2, Pages 299 - 318
Special Issue: Infection and Disease: Cause and Cure
Published Online: 17 Dec 2005
(google scholar)

Self-inactivating lentiviral vectors with enhanced transgene expression as potential gene transfer system in Parkinson's disease.
Déglon N, Tseng JL, Bensadoun JC, Zurn AD, Arsenijevic Y, Pereira de Almeida L, Zufferey R, Trono D, Aebischer P.
Hum Gene Ther. 2000 Jan 1;11(1):179-90.
PMID: 10646649 [PubMed - indexed for MEDLINE]
Viral vectors for in vivo gene transfer in Parkinson's disease: properties and clinical grade production
Mandel RJ, Burger C, Snyder RO.
Exp Neurol. 2008 Jan;209(1):58-71. Epub 2007 Aug 24. Review.
PMID: 17916354 [PubMed - indexed for MEDLINE]
About other vectors: HIV-1
The Journal of Immunology, 2005, 175: 112-123. 
Copyright © 2005 by
The American Association of Immunologists
Michele A. Kutzler*, Tara M. Robinson
Coimmunization with an Optimized IL-15 Plasmid Results in Enhanced Function and Longevity of CD8 T Cells That Are Partially Independent of CD4 T Cell
The Journal of Immunology, 2005, 175: 112-123. Copyright © 2005 by The American Association of Immunologists
(google scholar) (pour référencer un périodique scientifique, sans éléments superflus, se référer au document guide des références bibliographiques)
About other vectors: self-inactivating (SIN) lentiviral vector 

Self-inactivating lentiviral vectors with enhanced transgene expression as potential gene transfer system in Parkinson's disease.
Déglon N, Tseng JL, Bensadoun JC, Zurn AD, Arsenijevic Y, Pereira de Almeida L, Zufferey R, Trono D, Aebischer P.
Hum Gene Ther. 2000 Jan 1;11(1):179-90.
PMID: 10646649 [PubMed - indexed for MEDLINE]