Biblioguide en thérapie génique
3. GDNF comparaison cellules encapsulées/viral/pompe
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3. GDNF et thérapie génique: comparaison des techniques des cellules encapsulées/vecteurs viraux /protéine recombinante avec pompe 

Gilles Broccard and Keshav Krishnamani

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1/2 A. les mots-clés énoncés sont trop maigres

0/2 B. Les équations corresondantes aux mots-clés manquent et ne sont pas vraiment maîtrisées.

1/2 C. La restitution de la recherche documentaire montre une ballade avec Google, sans véritable jugement de la fiabilité des sources trouvées, ni de réelle tentative d'utilisation d'outils autres que Google. 

2/2 D. Les références sont correctes

1/2 E. Les réponses aux questions sont correctes et vont dans le sens d'une synthèse de la comparaison des techniques, mais les affirmations ne sont jamais référencées. Il y a des copier-coller sans guillemets et sans source, ce qui constitue un acte de plagiat.

1/2 F. La restitution écrite de la démarche de recherche d'information est désordonnée, le lecteur a du mal à percevoir une méthode de recherche.

Les nices links sont intéressants.

6 pts

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

Penser au pluriel, aux adjectifs, aux noms, à l'anglais, au français

* GDNF

*"Glial cell line-derived neurotrophic factor"

*"cell encapsulated GDNF"

- ce sont les cellules qu'on encapsule, pas le GDNF! cette expression est fausse.

- on pourrait mettre:  cell encapsulation, cell entrapment, cell confinement, microencapsulation, encapsulated cell(s)

* GDNF lentiviral delivery, synonymes?

On aimerait voir des mots-clés correspondants à protéine recombinante avec pompe?

 

3.2 Equations testées dans quel outil de recherche documentaire

(Penser aux e-books, catalogue NEBIS, bases de données multidisciplinaires, bases de données spécialisées, google, google scholar, forum, personne ressources, catalogues d'autres bibliothèques)

Google:

* "Glial cell line-derived neurotrophic factor" OR GDNF

Pubmed searches: 

* GDNF AND delivery

* (Comparative[Title] AND study[Title] AND GDNF[Title] AND delivery[Title] AND systems[Title] AND CNS[Title]) AND (polymer[Title] AND rods[Title] AND encapsulated[Title] AND cells[Title] AND lentiviral[Title] AND vectors[Title])

Cette équation est reconstituée de la référence [7]... difficile de croire au vu des mots-clés présentés, qu'elle a éé utilisée pour trouver de l'information? Elle est de plus inexacte, car si on l'utilise comme elle est écrite, sans parenthèse, et que avec des AND, on obtient dans n'importe quel outil de recherche (catalogue, BDB, moteur de recherche) beaucoup trop de résultats qui ne sont pas du tout pertinents. Une possiblité serait:

(comparative study) AND (GDNF delivery systems) AND ("polymer rods" OR"encapuslated cells" OR "lentiviral vectors")


3.3 Bibliographie suggérée

[1] Sajadi et al., 2006 A. Sajadi, J.-C. Bensadoun, B.L. Schneider, C. Lo Bianco and P. Aebischer, Transient striatal delivery of GDNF via encapsulated cells leads to sustained behavioral improvement in a bilateral model of Parkinson disease, Neurobiol. Dis. 22 (2006), pp. 119–129.

Found by: ScienceDirect

[2] Lysaght and Aebischer, 1999 M.J. Lysaght and P. Aebischer, Encapsulated cells as therapy, Sci. Am. 280 (1999), pp. 76–82. View Record in Scopus | Cited By in Scopus (37)

Found by: ScienceDirect + Scopus

[3] Olle Lindvall and Lars U. Wahlberg. Encapsulated cell biodelivery of GDNF: A novel clinical strategy for neuroprotection and neuroregeneration in Parkinson's disease? Experimental Neurology Volume 209, Issue 1, January 2008, Pages 82-88

[4] Kordower et al., 2000.Neurodegeneration Prevented by Lentiviral Vector Delivery of GDNF in primate models of Parkinson's disease.Science 27 October 2000:Vol. 290. no. 5492, pp. 767 - 773.

Found by: http://www.sciencemag.org

[5] McBride et al.,2006.Viral delivery of glial cell line-derived neurotrophic factor improves behavior and protects striatal neurons in a mouse model of Huntington's disease.

[6] The als newsletter.ALS Newsletter August 1999 v4 n4.

Found by: http://www.als-mda.org/Publications/als/als4_4.html,

- date de consultation?  dernière mise à jour? (voir document pour la citation d'un site web).

- ce site n'est pas vraiment scientifique, il y a un problème de fiabilité des sources... puisqu'on y trouver des infos du style sur la foi de M. Harwood: "M. Harwood cites religious faith and the support of family and friends as being responsible for his positive mental stance. He gives special credit to his wife for helping him to remain upbeat"

[7]Aebischer et al.,2003.Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors. Journal of Controlled Release Volume 87, Issues 1-3, 21 February 2003, Pages 107-115.

Found by: pubmed

 

3.4 GDNF and Genetic Therapy: A Comparison of delivery methods

Attention: Ou SONT LES SOURCES???? IL FAUT CITER!

The aim of this short research project is to understand the various methods of GDNF factor delivery and to compare the methods in terms of their efficiency, advantages and drawbacks.

GDNF - What is it ?

Glial cell line-derived neurotrophic factor (GDNF) is a naturally occurring growth factor that proved capable of protecting and promoting the survival of motor neurons in animal studies. A growth factor is a growth inducing protein found in the human body. There was a growing interest in these naturally occurring proteins that have a supportive, reparative or protective role for motor neurons in animals.

 

Fig 1: GDNF protein structure (réf?)

 

What is Parkinsons disease and Why the need of GDNF?

 

Methods of GDNF delivery: 

Three major methods of GDNF delivery have been explored:

 * Viral vector delivery

 * Encapsulated cell delivry

 * Pump delivery

 

Approaches to GDNF delivery: Viral therapy, encapsulated cell therapy and pump system for GDNF injection

Fig. 2: Approaches to GDNF delivery (réf?)

Encapsulated cell delivery of GDNF: 

The ECB technology consists of a catheter-like device, less than 1 mm in diameter, suitable for stereotactic implantation in the striatum. The approximately 1.5-cm-long active portion comprises a perm-selective hollow-fiber membrane, which allows for the inward diffusion of nutrients from the surrounding brain and the outward diffusion of GDNF. The long-term survival of the genetically modified human cell line is optimized by the attachment to an artificial matrix. The membrane forms an immunoisolatory barrier which prevents rejection of the allogeneic cell line. In addition, the attachment to a flexible tether allows for the implantation, positioning, and retrieval of the device and the encapsulated genetically modified cells.(réf?) ou sont les guillemets? copié-colllé oK, mais avec des guillemets

 

Fig. 3: Cell Encapsulation Method (réf?)

Viral vector delivery of GDNF: 

Viral vector delivery of GDNF is mainly used as a powerful tool to deliver trophic molecules to the central nervous system (CNS) in a site-specific manner. For exemple, delivery using lentiviral vectors was tested for its trophic effects upon degenerating nigrostriatal neurons in nonhuman primate models of Parkinson's disease(PD). For Huntington’s disease (HD), a neurological disorder resulting from a trinucleotide repeat expansion in the gene that encodes for the protein huntingtin, AAV ( adeno associated virus) -GDNF have been used to prevent  neuronal atrophy.(réf?)

One of the strategy to treat Amyotrophic lateral sclerosis (ALS) based on GDNF viral delivery:(réf?)

  1. Immature muscle cells (myoblasts) are infected with a modified virus carrying the gene for GDNF.
  2. The infected myoblasts are injected into the muscles of mice with a hereditary form of ALS.
  3. The injected cells fuse with existing muscle cells and begin producing and secreting GDNF, which is taken up by the endings of nerve fibers.
  4. GDNF is then transported through the nerve cell to the nerve cell body, where it helps to keep the cell alive.

 

 

Pump method of GDNF delivery:

 

 

 

Comparison of the various methods:

In the case of Parkinson's disease, polymer rods, genetically modified encapsulated cells and lentiviral vectors has been analyzed for its ability to release GDNF in the striatum of rats. Results show that GDNF expression (detected at a distance of 4mm, one week post-surgery), remains stable with the different methods. At 4 weeks GDNF staining diminished with rods and to a lesser extent with encapsulated cells, whereas it increased with lentiviral vectors. All three methods investigated allow striatal delivery of GDNF, but the time during which it needs to be released will determine the approach chosen for clinical application. (réf?)

 

 

                                                                                       figure (réf?)

Check these nice Links

* A video on GDNF delivery:

www.videojug.com/expertanswer/physical-treatments-for-parkinsons-2/how-is-gdnf-surgery-used-to-treat-people-with-parkinsons

*Link to the GDNF sequence:

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2668

 

 

 

 

 
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