Therapeutic targets and investigated treatments for Ataxia-Telangiectasia

ABSTRACT

Introduction: Ataxia-Telangiectasia (A-T) is an autosomal recessive multisystem disease affecting the brain, immune system, lungs, liver and also characterised by an enhanced risk of lymphoid and other tumours. At present there is no cure for A-T with management relying on supportive care using symptom-specific medications. Identification of the gene defective in this syndrome, ATM, and further characterization of the disorder together with greater insight into the function of the ATM protein has provided greater opportunity for the development of potential therapies.

Areas covered: Here we review conventional as well as more recently developed approaches to manage the symptoms of patients with A-T. In addition we explore ongoing and potential strategies for therapy involving gene correction, stem cells and use of antioxidants and anti-inflammatory agents.

Expert opinion: Prevention or arrest of the progressive neurodegeneration, the most debilitating feature of A-T, represents a major goal in the development of a cure for this disorder. However, since lung disease and increased risk of cancer are responsible for the majority of mortality in A-T, a greater understanding of these pathologies together with more effective approaches to treatment is required in the overall management of patients.

KEYWORDS:

• Ataxia-telangiectasia
• ATM protein
• neurodegeneration
• lung disease
• liver disease
• clinical trials
• oxidative stress
• steroids

Article highlights

• There is no cure for ataxia-telangiectasia but supportive care is available to treat specific symptoms

• Ataxia-telangiectasia is a multisystem disease affecting the brain, immune system, lungs and liver

• There is increasing evidence for involvement of oxidative stress in this disorder

• Progress to date using clinical trials suggest that prophylactic antibiotics and combinations of anti-oxidants and anti-inflammatory drugs may be beneficial in slowing the progress of the disorder

• Potential therapies include the use of stem cells and readthrough compounds

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

We acknowledge funding from the National Health and Medical Research Council (NHMRC) (GNT1020028), Australia, BrAshA-T Foundation, Australia (RM2016001474), and The A-T Children’s Project, USA (RM2016000563).