MPS VI gene therapy pre-clinical model

• June 7th, 2009

Mol Genet Metab. 2009 Jun;97(2):102-8. Epub 2009 Feb 27.
Lentiviral-mediated correction of MPS VI cells and gene transfer to joint tissues.
Byers S, Rothe M, Lalic J, Koldej R, Anson DS.

In this publication, the authors use a lentivirus to tranduce human fibroblasts and chondrocytes, as well as the synovial membrane and the fascia in injected rat joints.

Click this link to see the most recent online abstracts of major genetics journals.

Philippe Campeau

Mefolinate (5-methyltetrahydrofolate) as a treatment of severe MTHFR deficiency

• June 29th, 2008

Li, D. et al. Mefolinate (5-methyltetrahydrofolate), but not folic acid, decreases mortality in an animal model of severe methylenetetrahydrofolate reductase deficiency. Journal of Inherited Metabolic Disease Volume 31, Number 3 / June, 2008
In a mouse model of severe MTHFR deficiency, Mefolinate administration to the mother improved survival and cerebellar morphology in the pups. This agent could potentially be used eventually in clinical trials for the rare patients with severe MTHFR deficiency.
Thank you very much in advance for your contributions to this blog (Click on login to register and post a comment).

Click this link to see the most recent online abstracts of major genetics journals.

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Reversion of white matter changes with treatment of HMG-CoA lyase deficiency.

• December 19th, 2007

Pediatr Neurol. 2007 Jul;37(1):47-50.

3-Hydroxy-3-methylglutaryl coenzyme a lyase deficiency with reversible white
matter changes after treatment.

Zafeiriou DI, Vargiami E, Mayapetek E, Augoustidou-Savvopoulou P, Mitchell GA.

Click this link to see the most recent online abstracts of major genetics journals.
Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Antioxidants in tyrosinemia type 1

• December 7th, 2007

Chantale Langlois, Rossana Jorquera, Diana Orejuela, Anne Bergeron, Milton J. Finegold, William J. Rhead and Robert M. Tanguay,
Rescue from neonatal death in the murine model of hereditary tyrosinemia by glutathione monoethylester and vitamin C treatment,
Molecular Genetics and MetabolismIn Press, Corrected Proof, , Available online 26 November 2007.
(http://www.sciencedirect.com/science/article/B6WNG-4R70K78-2/2/86c9b26444612b49174abacbbe922884)
In this article, the authors describe the administration of antioxidants to a mouse model of tyrosinemia type 1. The treatment prevented neonatal death, but the disease still progressed in the mice. Perhaps antioxidants could be used in the future in conjunction with NTBC, if further experiments in mice show that combination therapy decreases the incidence of hepatocellular carcinoma and hepatic dysplasia.
Thank you very much in advance for your contributions to this blog (Click on login to register and post a comment).

Click this link to see the most recent online abstracts of major genetics journals.

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator 

WORLD symposium abstracts

• November 26th, 2007

The Lysosomal Disease Network’s 2006 WORLD Symposium was held at Disney World in Orlando, Florida (December 7–9, 2006). The 4th Symposium will be held on February 13–15, 2008, at the Venetian Hotel in Las Vegas, Nevada.
www.LysosomalDiseaseNetwork.org.

Abstracts can be found in the December issue of Molecular Genetics and Metabolism

Thank you very much in advance for your contributions to this blog (Click on login to register and post a comment).

Click this link to see the most recent online abstracts of major genetics journals.

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator
 

Gene therapy to prevent immune response to enzyme replacement therapy

• October 14th, 2007

Enhanced Response to Enzyme Replacement Therapy in Pompe Disease after the Induction of Immune Tolerance
Baodong Sun, Andrew Bird, Sarah P. Young, Priya S. Kishnani, Y.-T. Chen, and Dwight D. Koeberl
Am. J. Hum. Genet., 81:1042-1049, 2007

In this puplication, investigators from Duke University administered an AAV encoding alpha-glucosidase(GAA) to GAA-knockout mice. This prevented the antibody response to subsequently administered enzyme replacement therapy.

Thank you very much in advance for your contributions to this blog (Click on login to register and post a comment).

Click this link to see the most recent online abstracts of major genetics journals.
Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Enzyme replacement therapy in ectodermal dysplasia

• October 2nd, 2007

Significant Correction of Disease after Postnatal Administration of Recombinant Ectodysplasin A in Canine X-Linked Ectodermal Dysplasia

Margret L. Casal, John R. Lewis, Elizabeth A. Mauldin, Aubry Tardivel, Karine Ingold,
Manuel Favre, Fabrice Paradies,* Ste´phane Demotz, Olivier Gaide, and Pascal Schneider

The American Journal of Human Genetics, volume 81 (2007)
This paper describes the application of enzyme replacement therapy for X-linked hypohidrotic ectodermal dysplasia in dogs. Ectodysplasin A fused to the Fc portion of human immunoglobulin G1 was administered to the dogs in th neonatal period. This treatment improved the teeth  weight gain, restored lacrimation, preventing eye infections and keratoconjuctivitis sicca, induced the formation of moderate numbers of functional sweat glands, and significantly improved mucociliary clearance in the respiratory tract that correlated with the marked decrease of pulmonary diseases in the treated dogs.
Thank you very much in advance for your contributions to this blog (Click on login to register and post a comment).

Click this link to see the most recent online abstracts of major genetics journals.

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Use of N-carbamylglutamate

• May 20th, 2007

A trial with N-carbamylglutamate may not detect all patients with NAGS deficiency and neonatal onset
A. Nordenström, M. Halldin, B. Hallberg & J. Alm
Journal of Inherited Metabolic Disease
The patient described in this paper has N-Acetylglutamate synthase deficiency. However, he did not initially respond to N-carbamylglutamate. Therefore, the authors recommend that conventional hyperammonemia treatment should not be delayed by a N-carbamylglutamate loading test, but that this drug should still be included in the initial treatment of patients with hyperammonemia of unknown cause.

Thank you very much in advance for your contributions to this blog (Click on login to register and post a message).

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator
 

Primary hyperoxaluria mouse model and gene therapy.

• January 21st, 2007

Primary hyperoxaluria mouse model and gene therapy.
Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18249-54.

Alanine-glyoxylate aminotransferase-deficient mice, a model for primary
hyperoxaluria that responds to adenoviral gene transfer.

Salido EC, Li XM, Lu Y, Wang X, Santana A, Roy-Chowdhury N, Torres A, Shapiro
LJ, Roy-Chowdhury J.
In this important PNAS paper, the authors describe the creation of a mouse model for primary hyperoxaluria type 1. They also provide a proof of concept for liver directed gene therapy of primary hyperoxaluria using an adenoviral vector. However, I would have liked to see if the vector-treated mice were protected against ethylene glycol induced nephrocalcinosis.

For more information on primary hyperoxaluria, you can refer to chapter 133 of OMMBID.

Thank you very much in advance for your contributions to this blog (Click on login to register and post a message).
Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator