8. Parkinson et lentiviraux. Avec quel(s) lentivirus? Avec quels résultats?

Etudiants Adriana De Pesters / Jonathan Bernard

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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

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Company: Oxford Biomedica
Product: ProSavin
Lentiviral vector: EIAV

" PRODUCT DESCRIPTION
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

MARKET
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

TECHNICAL DESIGN
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

CLINICAL STATUS
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

DEVELOPMENT AND COMMERCIALISATION STRATEGY
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 "

MORE INFORMATION ABOUT THE CLINICAL TRIAL

"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. < http://www.oxfordbiomedica.co.uk/ProSavin.asp >. Consulté le 08.11.08

2. Source: Clinical trials Gov. < http://clinicaltrials.gov/ct2/show/NCT00627588?term=gene+therapy+and+parkinson&rank=2 >.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

company,industry

clinical trials,clinical applications

EIAV, Equine Infectious Anemia Virus

Oxford biomedica

8.2 Equations testées dans quel outil de recherche documentaire

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]