schliessen

Filtern

 

Bibliotheken

ProSavin a gene therapy approach for Parkinson's disease

L-Dopa has remained the primary standard of care for Parkinson's disease (PD) for the last 40 years. Although highly efficadous in the early stages of disease, it is assodated with debilitating long term side effects, such as dyskine-sias. Therapeutic strategies that aim to provide a constant dopami... Full description

Journal Title: Human gene therapy 2009-11-01, Vol.20 (11), p.1391-1391
Main Author: Jarraya, B
Other Authors: Lepitit, H , Ralph, S , Tani, N , Boulet, S , Jan, C , Bonvento, G , Miskin, J , Gurruchaga, J-M , Vinti, M , Fenelon, G , Brugiere, P , Kingsman, S , Hantraye, P
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 1043-0342
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_proquest_miscellaneous_21222497
title: ProSavin a gene therapy approach for Parkinson's disease
format: Article
creator:
  • Jarraya, B
  • Lepitit, H
  • Ralph, S
  • Tani, N
  • Boulet, S
  • Jan, C
  • Bonvento, G
  • Miskin, J
  • Gurruchaga, J-M
  • Vinti, M
  • Fenelon, G
  • Brugiere, P
  • Kingsman, S
  • Hantraye, P
subjects:
  • Primates
ispartof: Human gene therapy, 2009-11-01, Vol.20 (11), p.1391-1391
description: L-Dopa has remained the primary standard of care for Parkinson's disease (PD) for the last 40 years. Although highly efficadous in the early stages of disease, it is assodated with debilitating long term side effects, such as dyskine-sias. Therapeutic strategies that aim to provide a constant dopamine level in the striatum have been hypothesized to provide therapeutic benefits with reduced side effects. We have developed a lentiviral vector (ProSavin) derived from the equine infectious anaemia virus (EIAV) expressing the three key dopamine biosynthetic enzymes (tyrosine hydroxylase, aromatic L-amino acid decarboxylase and GTP cyclohydrolase-1). ProSavin has been demonstrated to mediate dopamine production and cause long term (>2 years) behavioural correction in the gold standard, MPTP non human primate (NHP) model of PD. Further studies have also demonstrated that ProSavin can prevent or reduce dyskinesias in NHP models. A phase I/II clinical trial to evaluate the safety and efficacy in late stage PD patients was initiated in Dec 2007. The trial is designed to evaluate the safety and efficacy profile of ProSavin following bilateral administration to the sensorimotor putamen of mid to late stage PD patients. To date, two dose levels have been evaluated and have been demonstrated to be well tolerated with no serious adverse events reported. In the first cohort of patients that received a low dose of ProSavin a -30% improvement in motor function was observed by 3 months post treatment, as assessed by UPDRS Part III scores, and this was sustained up to 12 months. In the second cohort of patients a similar level of improvement has been observed at 3 months post treatment. A summary of these early clinical results will be presented at the meeting.
language: eng
source:
identifier: ISSN: 1043-0342
fulltext: no_fulltext
issn:
  • 1043-0342
  • 1557-7422
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.2643087
LOCALfalse
PrimoNMBib
record
control
sourceidproquest
recordidTN_cdi_proquest_miscellaneous_21222497
sourceformatXML
sourcesystemPC
sourcerecordid21222497
originalsourceidFETCH-proquest_miscellaneous_212224970
addsrcrecordideNqNi7sOgkAQAC9GE5-l_VVagXsLCNRGY2mivdnoKijc4a2Y-Pda-AFWM8WMUlMDoYEsXxRtHSJAHkKOSUcNTJKkQRojdr8OcRRAFGNfDUVuACZKlulAZTvv9vQqrSZ9Zcv6WbCn5q2pabyjU6Evzusd-Xtpxdm56HMpTMJj1btQJTz5caRmm_VhtQ2-26NleR7rUk5cVWTZtXJEg4hxnsLf4Qd7ID8y
sourcetypeAggregation Database
isCDItrue
recordtypearticle
pqid21222497
display
typearticle
titleProSavin a gene therapy approach for Parkinson's disease
creatorJarraya, B ; Lepitit, H ; Ralph, S ; Tani, N ; Boulet, S ; Jan, C ; Bonvento, G ; Miskin, J ; Gurruchaga, J-M ; Vinti, M ; Fenelon, G ; Brugiere, P ; Kingsman, S ; Hantraye, P
creatorcontribJarraya, B ; Lepitit, H ; Ralph, S ; Tani, N ; Boulet, S ; Jan, C ; Bonvento, G ; Miskin, J ; Gurruchaga, J-M ; Vinti, M ; Fenelon, G ; Brugiere, P ; Kingsman, S ; Hantraye, P
descriptionL-Dopa has remained the primary standard of care for Parkinson's disease (PD) for the last 40 years. Although highly efficadous in the early stages of disease, it is assodated with debilitating long term side effects, such as dyskine-sias. Therapeutic strategies that aim to provide a constant dopamine level in the striatum have been hypothesized to provide therapeutic benefits with reduced side effects. We have developed a lentiviral vector (ProSavin) derived from the equine infectious anaemia virus (EIAV) expressing the three key dopamine biosynthetic enzymes (tyrosine hydroxylase, aromatic L-amino acid decarboxylase and GTP cyclohydrolase-1). ProSavin has been demonstrated to mediate dopamine production and cause long term (>2 years) behavioural correction in the gold standard, MPTP non human primate (NHP) model of PD. Further studies have also demonstrated that ProSavin can prevent or reduce dyskinesias in NHP models. A phase I/II clinical trial to evaluate the safety and efficacy in late stage PD patients was initiated in Dec 2007. The trial is designed to evaluate the safety and efficacy profile of ProSavin following bilateral administration to the sensorimotor putamen of mid to late stage PD patients. To date, two dose levels have been evaluated and have been demonstrated to be well tolerated with no serious adverse events reported. In the first cohort of patients that received a low dose of ProSavin a -30% improvement in motor function was observed by 3 months post treatment, as assessed by UPDRS Part III scores, and this was sustained up to 12 months. In the second cohort of patients a similar level of improvement has been observed at 3 months post treatment. A summary of these early clinical results will be presented at the meeting.
identifier
0ISSN: 1043-0342
1EISSN: 1557-7422
2DOI: 10.1089/hum.2009.0925
languageeng
subjectPrimates
ispartofHuman gene therapy, 2009-11-01, Vol.20 (11), p.1391-1391
lds50peer_reviewed
links
openurl$$Topenurl_article
thumbnail$$Usyndetics_thumb_exl
search
creatorcontrib
0Jarraya, B
1Lepitit, H
2Ralph, S
3Tani, N
4Boulet, S
5Jan, C
6Bonvento, G
7Miskin, J
8Gurruchaga, J-M
9Vinti, M
10Fenelon, G
11Brugiere, P
12Kingsman, S
13Hantraye, P
title
0ProSavin a gene therapy approach for Parkinson's disease
1Human gene therapy
descriptionL-Dopa has remained the primary standard of care for Parkinson's disease (PD) for the last 40 years. Although highly efficadous in the early stages of disease, it is assodated with debilitating long term side effects, such as dyskine-sias. Therapeutic strategies that aim to provide a constant dopamine level in the striatum have been hypothesized to provide therapeutic benefits with reduced side effects. We have developed a lentiviral vector (ProSavin) derived from the equine infectious anaemia virus (EIAV) expressing the three key dopamine biosynthetic enzymes (tyrosine hydroxylase, aromatic L-amino acid decarboxylase and GTP cyclohydrolase-1). ProSavin has been demonstrated to mediate dopamine production and cause long term (>2 years) behavioural correction in the gold standard, MPTP non human primate (NHP) model of PD. Further studies have also demonstrated that ProSavin can prevent or reduce dyskinesias in NHP models. A phase I/II clinical trial to evaluate the safety and efficacy in late stage PD patients was initiated in Dec 2007. The trial is designed to evaluate the safety and efficacy profile of ProSavin following bilateral administration to the sensorimotor putamen of mid to late stage PD patients. To date, two dose levels have been evaluated and have been demonstrated to be well tolerated with no serious adverse events reported. In the first cohort of patients that received a low dose of ProSavin a -30% improvement in motor function was observed by 3 months post treatment, as assessed by UPDRS Part III scores, and this was sustained up to 12 months. In the second cohort of patients a similar level of improvement has been observed at 3 months post treatment. A summary of these early clinical results will be presented at the meeting.
subjectPrimates
issn
01043-0342
11557-7422
fulltextfalse
rsrctypearticle
creationdate2009
recordtypearticle
recordideNqNi7sOgkAQAC9GE5-l_VVagXsLCNRGY2mivdnoKijc4a2Y-Pda-AFWM8WMUlMDoYEsXxRtHSJAHkKOSUcNTJKkQRojdr8OcRRAFGNfDUVuACZKlulAZTvv9vQqrSZ9Zcv6WbCn5q2pabyjU6Evzusd-Xtpxdm56HMpTMJj1btQJTz5caRmm_VhtQ2-26NleR7rUk5cVWTZtXJEg4hxnsLf4Qd7ID8y
startdate20091101
enddate20091101
creator
0Jarraya, B
1Lepitit, H
2Ralph, S
3Tani, N
4Boulet, S
5Jan, C
6Bonvento, G
7Miskin, J
8Gurruchaga, J-M
9Vinti, M
10Fenelon, G
11Brugiere, P
12Kingsman, S
13Hantraye, P
scope
07QO
17TK
27U9
38FD
4FR3
5H94
6P64
7RC3
sort
creationdate20091101
titleProSavin a gene therapy approach for Parkinson's disease
authorJarraya, B ; Lepitit, H ; Ralph, S ; Tani, N ; Boulet, S ; Jan, C ; Bonvento, G ; Miskin, J ; Gurruchaga, J-M ; Vinti, M ; Fenelon, G ; Brugiere, P ; Kingsman, S ; Hantraye, P
facets
frbrtype5
frbrgroupidcdi_FETCH-proquest_miscellaneous_212224970
rsrctypearticles
prefilterarticles
languageeng
creationdate2009
topicPrimates
toplevelpeer_reviewed
creatorcontrib
0Jarraya, B
1Lepitit, H
2Ralph, S
3Tani, N
4Boulet, S
5Jan, C
6Bonvento, G
7Miskin, J
8Gurruchaga, J-M
9Vinti, M
10Fenelon, G
11Brugiere, P
12Kingsman, S
13Hantraye, P
collection
0Biotechnology Research Abstracts
1Neurosciences Abstracts
2Virology and AIDS Abstracts
3Technology Research Database
4Engineering Research Database
5AIDS and Cancer Research Abstracts
6Biotechnology and BioEngineering Abstracts
7Genetics Abstracts
jtitleHuman gene therapy
delivery
delcategoryRemote Search Resource
fulltextno_fulltext
addata
au
0Jarraya, B
1Lepitit, H
2Ralph, S
3Tani, N
4Boulet, S
5Jan, C
6Bonvento, G
7Miskin, J
8Gurruchaga, J-M
9Vinti, M
10Fenelon, G
11Brugiere, P
12Kingsman, S
13Hantraye, P
formatjournal
genrearticle
ristypeJOUR
atitleProSavin a gene therapy approach for Parkinson's disease
jtitleHuman gene therapy
date2009-11-01
risdate2009
volume20
issue11
spage1391
epage1391
pages1391-1391
issn1043-0342
eissn1557-7422
abstractL-Dopa has remained the primary standard of care for Parkinson's disease (PD) for the last 40 years. Although highly efficadous in the early stages of disease, it is assodated with debilitating long term side effects, such as dyskine-sias. Therapeutic strategies that aim to provide a constant dopamine level in the striatum have been hypothesized to provide therapeutic benefits with reduced side effects. We have developed a lentiviral vector (ProSavin) derived from the equine infectious anaemia virus (EIAV) expressing the three key dopamine biosynthetic enzymes (tyrosine hydroxylase, aromatic L-amino acid decarboxylase and GTP cyclohydrolase-1). ProSavin has been demonstrated to mediate dopamine production and cause long term (>2 years) behavioural correction in the gold standard, MPTP non human primate (NHP) model of PD. Further studies have also demonstrated that ProSavin can prevent or reduce dyskinesias in NHP models. A phase I/II clinical trial to evaluate the safety and efficacy in late stage PD patients was initiated in Dec 2007. The trial is designed to evaluate the safety and efficacy profile of ProSavin following bilateral administration to the sensorimotor putamen of mid to late stage PD patients. To date, two dose levels have been evaluated and have been demonstrated to be well tolerated with no serious adverse events reported. In the first cohort of patients that received a low dose of ProSavin a -30% improvement in motor function was observed by 3 months post treatment, as assessed by UPDRS Part III scores, and this was sustained up to 12 months. In the second cohort of patients a similar level of improvement has been observed at 3 months post treatment. A summary of these early clinical results will be presented at the meeting.
doi10.1089/hum.2009.0925