Genetic Modification Clinical Research Information System

• July 24th, 2006

GeMCRIS, a NIH initiative, is a comprehensive database of human gene therapy trials. It is easily searchable and very reliable.

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

Pyridoxine dependent epilepsy

• July 18th, 2006

Pyridoxine dependent epilepsy (PDE) was first described by Hunt in 1954. In 1969, Dr Scriver suggested that PDE was caused by reduced binding of pyridoxal phosphate to glutamate decarboxylase leading to buildup of excitotoxic glutamate and deficiency of inhibitory GABA in the brain.

 
In 2005, a group identified the gene ALDH7A1 encoding antiquitin (P6C-alpha-AASA dehydrogenase) as the culprit in PDE. This astute discovery was made following the report of pipecolic acid accumulation in PDE and by hypothesizing that P6C inactivates pyridoxal phosphate in a similar fashion as P5C in hyperprolinemia type II.
 

Nat Med. 2006 Mar;12(3):307-9. Epub 2006 Feb 19.
Mutations in antiquitin in individuals with pyridoxine-dependent seizures.
Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, Willemsen MA,
Omran H, Tacke U, Uhlenberg B, Weschke B, Clayton PT.

For great reviews, see:

J Inherit Metab Dis. 2006 Apr;29(2-3):317-26.
B(6)-responsive disorders: A model of vitamin dependency.
Clayton PT.

OMMBID chapter 86.1.
 

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

The Orphanet Journal of Rare Diseases

• July 13th, 2006

Orphanet continues its quest to to improve the management and treatment of genetic, auto-immune or infectious rare diseases, rare cancers, or not yet classified rare diseases.
It launched the Orphanet Journal of Rare Diseases. The editors in chief are Ségolène Aymé, Inserm, Hôpital Broussais; Bruno Dallapiccola, Istituto CSS-Mendel; and Dian Donnai,The Victoria University of Manchester.

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

Therapeutic gene causing lymphoma

• July 9th, 2006

Nature. 2006 Apr 27;440(7088):1123.
Gene therapy: therapeutic gene causing lymphoma.
Woods NB, Bottero V, Schmidt M, von Kalle C, Verma IM.
3 children who underwent gene therapy for X-linked Severe Combined Immunodeficiency (X-SCID),using therapeutic administration of the IL2RG gene, developped T-cell leukaemia.
In this article, the investigators conducted long term studies in a murine moodel of X-SCID using a similar treatment. One third of the mice developped T-cell lymphomas. This implicates IL2RG in the lymphomagenesis in this model. It underscores the requirement for long-term studies in animals before conducting human gene therapy trials.

For more information on the treatement of genetic disease and on X-SCID, see chapters 5 and 185 of OMMBID, respectively.
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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Canavan disease and the role of N-acetylaspartate in myelin synthesis

• July 5th, 2006

Canavan disease and the role of N-acetylaspartate in myelin synthesis
Namboodiri AM, Peethambaran A, Mathew R, Sambhu PA, Hershfield J, Moffett JR, Madhavarao CN.

Mol Cell Endocrinol. 2006 Jun 27;252(1-2):216-23

 
In this article, the authors give further proof that N-acetylaspartate acts as an acetate carrier from mitochondria to the cytosol, and is thus important for lipogenesis and myelination in the central nervous system.
They recall that in the brain of Canavan disease mice (APSA -/-), there was nearly an 80% reduction in free acetate levels.
Supplementing these mice with glyceryl triacetate increases the brain acetate levels without affecting N-acetylaspartate levels and without toxicity.

For more information on Canavan disease, see chapter 229 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