Leucine for Niemann-Pick Disease: Does it Help?

observational-study PMID: 34387740

Quick Summary: A study found that a form of leucine, called N-acetyl-L-leucine (NALL), improved symptoms and quality of life for people with Niemann-Pick disease type C (NPC). The benefits were seen within 6 weeks, but disappeared after stopping the treatment.

What The Research Found

Researchers looked at how NALL affected people with NPC. They found that NALL helped with:

Symptom Severity: People felt better overall.

Motor Function: They moved and functioned better.

Quality of Life: Their daily lives improved.

The study also showed that NALL was safe, with no serious side effects. However, the improvements went away after the treatment stopped, meaning ongoing treatment is likely needed.

Study Details

Who was studied: 33 people (aged 7-64) with NPC.

How long: The study lasted for 18 weeks. This included a baseline period, 6 weeks of treatment, and 6 weeks after stopping treatment.

What they took: Participants took NALL by mouth. Adults (13+) took 4 grams daily. Children (6-12) received a dose based on their weight.

What This Means For You

This research is specifically for people diagnosed with NPC. If you or a loved one has NPC, talk to your doctor about this study and whether NALL might be an option. It's important to note:

This is not a cure: The benefits stopped when the treatment did.

Talk to your doctor: This study is for a specific disease, and you should not self-treat.

Study Limitations

Small Study: Only a small number of people were in the study, so more research is needed.

No Placebo: The study didn't compare NALL to a "dummy" pill, so it's hard to know how much of the improvement was due to the treatment itself.

Short Term: The study only looked at the effects for a short time.

Age Range: The study included people of different ages, which could affect the results.

Key Findings

N-acetyl-L-leucine (NALL) showed statistically significant improvements in symptom severity, motor function, and quality of life in Niemann-Pick disease type C (NPC) patients aged 7–64 years. The clinical benefits were lost after a 6-week washout period, suggesting ongoing treatment is required. No serious adverse events were reported, indicating a favorable safety profile.

Study Design

This was a multinational, open-label, rater-blinded Phase II trial (NCT03759639) involving 33 NPC patients (32 included in primary analysis). Participants underwent three phases: baseline assessment, 6 weeks of NALL treatment, and a 6-week post-treatment washout. The primary endpoint was the Clinical Impression of Change in Severity (CI-CS), evaluated via blinded centralized raters comparing randomized video pairs of patients performing motor tests (8-Meter Walk or 9-Hole Peg Test). Secondary outcomes included cerebellar function scales, clinical global impression, and quality-of-life metrics.

Dosage & Administration

NALL was administered orally at 4 g/day for patients ≥13 years. For children aged 6–12 years, weight-tiered dosing was used (not specified in summary). Treatment duration was 6 weeks, followed by a 6-week washout period to assess sustained effects.

Results & Efficacy

Primary Endpoint: CI-CS mean difference of 0.86 (SD=2.52, 90% CI 0.25–1.75, p=0.029), indicating clinically meaningful improvement in symptom severity.
Secondary Endpoints: Improvements observed in cerebellar function scales, clinical global impression, and quality-of-life assessments, though specific metrics were not detailed.
Washout Effects: Benefits diminished after discontinuation, highlighting the need for continuous therapy.
Safety: No serious adverse events; NALL was well-tolerated.

Limitations

Open-label design: Lack of placebo control introduces potential bias, though raters were blinded.
Small sample size: Only 33 patients enrolled, limiting generalizability.
Short duration: Long-term efficacy and safety beyond 6 weeks remain unassessed.
Heterogeneous population: Age range (7–64 years) and concurrent therapies may confound results.
Unspecified pediatric dosing: Weight-tiered regimens for 6–12-year-olds lacked quantitative details.

Clinical Relevance

This study suggests NALL may offer rapid, measurable symptom relief for NPC patients, particularly in motor function and quality of life. However, the absence of placebo control and short follow-up period necessitate cautious interpretation. For supplement users, these results are relevant only to NPC patients under medical supervision, not for general health or athletic performance. The temporary effect underscores the importance of sustained treatment, while the safety profile supports further investigation in larger, placebo-controlled trials.

Source: PubMed | Date: 2022 | Study Type: Observational (Phase II)