The patient told me about a study in which two Parkinson’s patients were reportedly “cured” of the disease with an amino acid. Below are my findings on this topic; the individual studies are attached further down.
Acetyl-lysine in Parkinson’s disease
The central study is indeed the Nature Communications case report from 2024 involving two iRBD patients (a prodromal stage preceding Parkinson’s disease), and there are additional indications relating to RBD in Parkinson’s disease.
RBD stands for REM Sleep Behavior Disorder
It is a parasomnia in which the normal muscle atonia (paralysis of skeletal muscles) during REM sleep is absent.
Affected individuals act out their dreams – often very vividly, with intense emotions and aggressive behavior (hitting, kicking, shouting, jumping out of bed).
This frequently leads to injuries to the patient themselves or to the bed partner.
RBD is considered one of the strongest prodromal markers for synucleinopathies (in particular Parkinson’s disease, Dementia with Lewy bodies, and Multiple System Atrophy).
In isolated RBD (without other neurological symptoms), approximately 70–90 % of affected individuals develop one of these neurodegenerative diseases within 10–15 years.
Diagnosis is ideally made by polysomnography = sleep laboratory (demonstration of absent REM atonia plus motor activity during REM sleep).
Treatment (symptomatic):
- Clonazepam (0.5–2 mg at night) – classical first-line therapy
- Melatonin (3–12 mg at night) – often better tolerated and increasingly preferred
- Safety measures (separate beds for partners, mattress on the floor, removal of bed rails, etc.)
In more recent case reports on acetyl-DL-leucine (Tanganil), this very RBD symptomatology was considered the primary endpoint – with reports of a marked reduction in dream enactment and dream intensity.
Current review of the evidence in Parkinson’s disease
Robust evidence in the form of randomized, placebo-controlled trials for acetyl-DL-leucine in manifest Parkinson’s disease (motor symptoms or slowing of progression) is currently not available.
What does exist, however:
- Two well-documented case reports in patients with isolated REM Sleep Behavior Disorder (iRBD, prodromal stage of Parkinson’s disease) treated with acetyl-DL-leucine 5 g/day. Clinical improvements were observed, including reversibility of dopamine transporter loss on DAT-SPECT and stabilization of the pathological metabolic pattern on FDG-PET. (Oertel et al. (2024) Nature Communications https://www.nature.com/articles/s41467-024-51502-7)
- Another report on RBD in patients with Parkinson’s disease treated with acetyl-DL-leucine 5 g/day, describing subjective improvement of RBD symptoms over a longer period, but without a control group. (Likely the 2020 case or series mentioned in blogs and reviews, e.g. Science of Parkinson’s Blog https://scienceofparkinsons.com/2024/09/28/rbd)
This is clinically interesting and hypothesis-generating, but does not yet constitute proof of efficacy.
Which variant was used in the Parkinson-related studies?
Acetyl-DL-leucine (ADLL, racemate)
In the published case reports on iRBD and RBD in Parkinson’s disease, acetyl-DL-leucine (the racemate of the D- and L-forms) was used at a dose of 5 g/day. This corresponds to the well-known preparation Tanganil (approved mainly for vertigo/ataxia, discussed off-label in neurological indications).
N-acetyl-L-leucine (NALL, levacetylleucine)
The L-form alone is considered in more recent work (especially in Niemann–Pick type C and ataxias) to be the likely bioactive enantiomer. It is being further developed pharmaceutically (e.g. Aqneursa). However, in the published Parkinson/iRBD case reports, not the pure L-form but the racemate (ADLL) was used. The authors note that future studies should ideally be conducted with the bioactive enantiomer (acetyl-L-leucine).
N-acetyl-D-leucine (D-form)
The D-form alone does not currently play a leading role in the Parkinson’s discussion.
What exactly do the studies with 5 g/day show?
- In the Nature Communications report (2024), two patients with iRBD (prodromal stage): under ADLL 5 g/day there was a marked reduction of RBD symptoms (less aggressive dream content and enactment), reversibility of the previously progressive dopamine transporter loss in the striatum (DAT-SPECT), and stabilization of the Parkinson-typical metabolic pattern (FDG-PET). Observation period up to 22 months. (Oertel et al. (2024) Nature Communications https://www.nature.com/articles/s41467-024-51502-7)
- In addition, there are reports of RBD improvement in manifest Parkinson’s disease at the same dose, but in small case numbers without controls.
Personally, I consider these to be very strong data, even though they involve only two patients: reversal of DAT-SPECT findings in the brain is practically a complete reversal of existing neurodegeneration. Even if it is not full-blown Parkinson’s disease, I would in any case take this – a normal amino acid.
Practical interpretation
What can currently be stated with scientific integrity
- There is an interesting signal from case reports, particularly in the prodromal stage (iRBD), with objective imaging data. (Oertel et al. (2024) Nature Communications https://www.nature.com/articles/s41467-024-51502-7)
- The published dose of 5 g/day refers to acetyl-DL-leucine (racemate).
What remains open
- Whether there is a true slowing or even reversal of motor Parkinson’s symptoms must be investigated in controlled studies. Such studies are desirable and partly under discussion, but have not yet been completed.
- The L-form (NALL) is mechanistically favored and is being further developed in other indications; it could become relevant for Parkinson’s disease in the future.
Google CENSORSHIP!
Google censors my homepage quite a bit, sometimes I am not even able to find my articles on Google. So please sign up for the newsletter and share it with friends or via Facebook and use the search function on my website. Follow me on Twitter, where I also announce important articles.
