Year: 2024
Type: article
Abstract: Recently, N-acetyl-L-leucine has been reported to have disease-modifying effects in Niemann-Pick disease type C, a lysosomal storage disorder, in a randomized controlled trial. 1 Lysosomal dysfunction is also thought to be one of the underlying pathogenic mechanisms of Parkinson's disease (PD), which often manifests with rapid eye movement sleep behavior disorder (RBD) as prodrome.Oertel and colleagues 2 treated two individuals with isolated RBD (iRBD), hyposmia, and pathological dopamine-transporter single-photon emission computerized tomography (DAT-SPECT) with acetyl-DL-leucine (ADLL) (5 g/d; contains a racemate of acetyl-leucine, the inactive D-form, and the bioactive enantiomer, the L-form) for 18 and 22 months, respectively, and investigated its effect on disease progression using the following outcome parameters: RBD-severity sumscore (RBD-SS-3; a RBD diary filled by patient and bedpartner), DAT-SPECT imaging (performed in two centers) and metabolic "Parkinson-Disease-Pattern (PDRP)"-z-score in 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET).2 They report no side effects and that ADLL therapy improved the severity of RBD in terms of reduction of aggressive dream content and dream enactment, reversed the loss of striatal dopamine transporter binding, and stabilized the metabolic FDG-PET pattern.The authors acknowledge several limitations: the report encompassing only two cases without a placebo control; the lack of a pre-defined protocol for the timing of imaging assessment; the method of PDRP by FDG-PET being not yet fully established; the subjective nature of the RBD diary as outcome measure (in contrast to objective measures like polysomnography).Moreover, reduced dream-enacting behavior alone cannot be equated with improvement in RBD, and it is not yet clear that RBD severity (or the content of dreams in RBD) correlates well with overall disease progression and severity.
DOI: 10.1002/mdc3.14316
Authors: Bettina Balint, Kailash P. Bhatia
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4405831766