Pharmacological Interventions for Neurological Manifestations of Ataxia-Telangiectasia: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials
In brief
Pooled trials find no significant ataxia-score improvement with levacetylleucine
Across six randomized trials of drugs for ataxia-telangiectasia, two levacetylleucine trials showed no significant pooled improvement on an ataxia rating scale, with results varying substantially. A separate pooled analysis found better scores with erythrocyte-encapsulated dexamethasone, but neither trial met its primary neurological endpoint. The findings leave treatment effects uncertain and highlight the need for better outcome measures.
- Journal
- Cerebellum (London, England) (Q1)
- Published
- 31 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Muhammad Junaid Iqbal, Muteeba Azhar, Amina Hassan, Michele Menotta
- PMID
- 42965751
- DOI
- 10.1007/s12311-026-02108-w
Why clinicians should know about it
- Picked for Immunology and Allergy (top studies of the week, 1 November 2026): Systematic review evaluates treatments for neurologic manifestations of primary immunodeficiency
- Picked for Pediatrics and Child Health (top studies of the week, 1 November 2026): Evidence review addresses treatment of a childhood-onset chronic neurological disease
- Picked for Neurology (clinical) (top studies of the week, 1 November 2026): Clinical drug evidence for neurological ataxia manifestations
Abstract
Ataxia-telangiectasia (A-T) causes progressive neurological disability. Following two phase III trials published in 2026, this study is an updated randomized evidence for pharmacological interventions targeting neurological manifestations of A-T. PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Cochrane Library were searched. Eligible studies were RCTs in children or adults with A-T. Risk of bias was assessed using Cochrane RoB 2. N-acetyl-L-leucine/levacetylleucine SARA treatment effects were pooled using a random-effects generic inverse-variance model with restricted maximum likelihood (REML), with common-effect and Hartung-Knapp-Sidik-Jonkman sensitivity analyses. Secondary analyses pooled full-ICARS efficacy and safety outcomes from the two eDSP trials. Six RCTs evaluated oral betamethasone, N-acetyl-L-leucine/levacetylleucine, erythrocyte-encapsulated dexamethasone sodium phosphate (eDSP), and triheptanoin. Two crossover trials contributed to the SARA meta-analysis. The pooled REML effect was not significant (MD -0.90, 95% CI -3.20 to 1.40; p = 0.443; I²=75.8%). Two eDSP trials contributed comparable full-ICARS estimates in children aged 6-9 years; the conventional pooled result favored eDSP (MD -4.03, 95% CI -6.78 to -1.29). Neither eDSP trial met its prespecified primary neurological endpoint. Pooled eDSP risk ratios were 1.05 (0.94 to 1.17) for any treatment-emergent adverse event, 1.45 (0.995 to 2.12) for treatment-related events, and 0.94 (0.40 to 2.22) for serious adverse events. Betamethasone and triheptanoin were each represented by one RCT. Despite FDA approval of levacetylleucine for ataxia in A-T, pooled SARA effects remain inconsistent. The favorable secondary eDSP full-ICARS estimate does not supersede the unsuccessful primary trial analyses. Harmonized, feasible neurological outcome measures are needed.PROSPERO Registration NumberCRD420261474940.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.