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

Br Med Bull. 2007;81-82:129-47. doi: 10.1093/bmb/ldm012. Epub 2007 Jun 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ataxia Telangiectasia / diagnosis
  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia / therapy*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics
  • Child
  • Child, Preschool
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins / genetics
  • Diagnosis, Differential
  • Humans
  • Infant
  • Infant, Newborn
  • Mutation / genetics
  • Nerve Degeneration / prevention & control*
  • Phenotype
  • Protein Serine-Threonine Kinases / genetics
  • Tumor Suppressor Proteins / genetics


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases