Effects of Acetyl-DL-Leucine on Ataxia and Downbeat-Nystagmus in Six Patients With Ataxia Telangiectasia

. 2021 Oct 7;8830738211028394.
 doi: 10.1177/08830738211028394. Online ahead of print.

Effects of Acetyl-DL-Leucine on Ataxia and Downbeat-Nystagmus in Six Patients With Ataxia Telangiectasia

Adriana Brueggemann12, Antonela Bicvic32, Martina Goeldlin3, Roger Kalla3, Hassen Kerkeni3, Georgios Mantokoudis4, Mathias Abegg5, Miriam Kolníková6, Markus Mohaupt13, Tatiana Bremova-Ertl1378
Affiliations 

Affiliations

  • 1Department of Internal Medicine, Sonnenhofspital, Lindenhofgruppe, Bern, Switzerland.
  • 2Shares the first author place.
  • 3Department of Neurology, University Hospital Bern (Inselspital) and University of Bern, Bern, Switzerland.
  • 4Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University Hospital Bern (Inselspital) and University of Bern, Bern, Switzerland.
  • 5Department of Ophthalmology, University Hospital Bern (Inselspital) and University of Bern, Bern, Switzerland.
  • 6Comenius University Children's Hospital, Department of Child Neurology, Bratislava, Slovak Republic.
  • 7Center for Rare Diseases, Institute for Clinical Chemistry, University Hospital Bern (Inselspital) and University of Bern, Bern, Switzerland.
  • 8German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University Hospital, Campus Grosshadern, Munich, Germany.

Abstract

Background: There is no authorized treatment for ataxia telangiectasia (AT). As cerebellar symptoms of storage diseases were improved by acetyl-DL-leucine (ADLL), the authors hypothesized a symptomatic and disease-modifying effect in AT upon supplementation with ADLL.

Methods: Six patients were treated with ADLL 3 g/day for 1 week followed by 5g/day for 3 weeks to 1 year. Cerebellar ataxia was evaluated by validated scales. Gaze-holding, saccades and smooth pursuit were examined by video-oculography. Measurements took place at baseline, at 1 month of therapy in 5 patients, and after 6 and 12 months in 1 patient.

Results: The Scale for Assessment and Rating of Ataxia changed from the baseline, mean, (SD, min-max) of 22.1 (5.88, 11-28.5) to 18 points (5.39, 8.5-23.5) after 1 month on medication (P = .0028). All patients demonstrated gaze-holding deficits; 3 patients had central-position downbeat-nystagmus. Mean slow-phase velocity of this nystagmus with the gaze straight-ahead changed from 5.57°/s (1.8, 3.53-6.99) to 4.7°/s (0.79, 3.97-5.56) after 1 month on treatment (1.35, -2.56-4.17) (P = .046).

Interpretation: ADLL may improve ataxia and ocular stability in AT patients, while the molecular basis still remains to be elucidated. A multicentric, rater-blinded, phase II trial currently investigates the effects of acetyl-L-leucine in AT (NCT03759678).

Keywords: ataxia; cerebellum; neurodevelopment; pediatric; quality of life.