Acetyl-DL-leucine in two individuals with REM sleep behavior disorder improves symptoms, reverses loss of striatal dopamine-transporter binding and stabilizes pathological metabolic brain pattern—case reports

Wolfgang H. Oertel (), Annette Janzen, Martin T. Henrich, Fanni F. Geibl, Elisabeth Sittig, Sanne K. Meles, Giulia Carli, Klaus Leenders, Jan Booij, D. James Surmeier, Lars Timmermann and Michael Strupp ()
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Wolfgang H. Oertel: Philipps University of Marburg
Annette Janzen: Philipps University of Marburg
Martin T. Henrich: Philipps University of Marburg
Fanni F. Geibl: Philipps University of Marburg
Elisabeth Sittig: Philipps University of Marburg
Sanne K. Meles: University Medical Center Groningen
Giulia Carli: University Medical Center Groningen
Klaus Leenders: University Medical Center Groningen
Jan Booij: University of Amsterdam
D. James Surmeier: Northwestern University
Lars Timmermann: Philipps University of Marburg
Michael Strupp: LMU University Hospital, LMU

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: Abstract Isolated REM Sleep Behavior Disorder (iRBD) is considered a prodrome of Parkinson’s disease (PD). We investigate whether the potentially disease-modifying compound acetyl-DL-leucine (ADLL; 5 g/d) has an effect on prodromal PD progression in 2 iRBD-patients. Outcome parameters are RBD-severity sum-score (RBD-SS-3), dopamine-transporter single-photon emission computerized tomography (DAT-SPECT) and metabolic “Parkinson-Disease-related-Pattern (PDRP)”-z-score in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). After 3 weeks ADLL-treatment, the RBD-SS-3 drops markedly in both patients and remains reduced for >18 months of ADLL-treatment. In patient 1 (female), the DAT-SPECT putaminal binding ratio (PBR) decreases in the 5 years pretreatment from normal (1.88) to pathological (1.22) and the patient’s FDG-PET-PDRP-z-score rises from 1.72 to 3.28 (pathological). After 22 months of ADLL-treatment, the DAT-SPECT-PBR increases to 1.67 and the FDG-PET-PDRP-z-score stabilizes at 3.18. Similar results are seen in patient 2 (male): his DAT-SPECT-PBR rises from a pretreatment value of 1.42 to 1.72 (close to normal) and the FDG-PET-PDRP-z-score decreases from 1.02 to 0.30 after 18 months of ADLL-treatment. These results support exploration of whether ADLL may have disease-modifying properties in prodromal PD.

Date: 2024
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DOI: 10.1038/s41467-024-51502-7

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