Current and potential therapeutic strategies for the treatment of ataxia-telangiectasia

Lavin, Martin F., Gueven, Nuri, Bottle, Stephen and Gatti, Richard A. (2007) Current and potential therapeutic strategies for the treatment of ataxia-telangiectasia. British Medical Bulletin, 81-82 1: 129-147. doi:10.1093/bmb/ldm012


Author Lavin, Martin F.
Gueven, Nuri
Bottle, Stephen
Gatti, Richard A.
Title Current and potential therapeutic strategies for the treatment of ataxia-telangiectasia
Journal name British Medical Bulletin   Check publisher's open access policy
ISSN 0007-1420
1471-8391
Publication date 2007-06-23
Sub-type Article (original research)
DOI 10.1093/bmb/ldm012
Open Access Status Not Open Access
Volume 81-82
Issue 1
Start page 129
End page 147
Total pages 19
Editor N. Vetter
Place of publication London
Publisher Oxford University Press
Language eng
Subject 320799 Neurosciences not elsewhere classified
C1
730104 Nervous system and disorders
Abstract Ataxia-telangiectasia (A-T) is a rare autosomal recessive genetic disorder characterized by progressive neurodegeneration, a high risk of cancer and immunodeficiency. These patients are also hypersensitive to radiotherapy. The gene product defective in this syndrome, ATM (ataxia-telangiectasia mutated), normally recognizes DNA damage and signal to the DNA repair machinery and the cell cycle checkpoints to minimize the risk of genetic damage. No curative strategy for this disease exists. Treatment has focused on slowing the progress of the neurodegeneration; devising approaches for the treatment of tumours while minimizing side effects and treatment with immunoglobulin for the immunodeficiency. The most debilitating feature of this disorder is the progressive neurodegeneration due to loss of Purkinje cells in the cerebellum and malfunction of other neuronal cells. Correcting for the loss of Purkinje cells is technically very difficult and would require transplantation of embryonic stem cells. However, since it seems likely that oxidative stress may contribute to the neurodegeneration in A-T, potential therapies based on the use of antioxidants offer some hope. We describe the natural course of disease, some supportive therapeutic approaches already in use and those with potential based on our knowledge of molecular and cellular characteristics of this disorder.
Keyword Medicine, General & Internal
ataxia-telangiectasia
neurodegeneration
ATM
antioxidants
mutation-targeted therapy
Atm-deficient Mice
Dna-damage
Oxidative Stress
Ionizing-radiation
Splicing Mutations
Protein Expression
Gene-product
Mutant Mice
P53
Cancer
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2008 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Tue, 19 Feb 2008, 00:30:27 EST