The Effects of N-Acetyl-L-Leucine on the Symptoms in Patients with Spinocerebellar Ataxia: A Four-Case Experimental Study

Sahebkar, Amirhossein; Beiraghi Toosi, Mehran; Nikbakht, Mohammadreza; Akhlaghi, Saeed; Shirzad, Rojin; Saberi-Karimian, Maryam

doi:10.22038/jpp.2026.96200.5676

The Effects of N-Acetyl-L-Leucine on the Symptoms in Patients with Spinocerebellar Ataxia: A Four-Case Experimental Study

Document Type : original article

Authors

Amirhossein Sahebkar ¹^{, 2}^{, 3}^{, 4}

Mehran Beiraghi Toosi ⁵ ^¶

Mohammadreza Nikbakht ⁶^{, 7}

Saeed Akhlaghi ⁸

Rojin Shirzad ⁶^{, 7}

Maryam Saberi-Karimian ⁷

¹ Applied Biomedical Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

² Centre for Research Impact and Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India.

³ Center for Innovation and Inclusive Research, Sharda University, Greater Noida, Uttar Pradesh, India.

⁴ Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

⁵ Rare Pediatric Neurological Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

⁶ Endoscopic and Minimally Invasive Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

⁷ Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

⁸ Department of Biostatistics, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran.

10.22038/jpp.2026.96200.5676

Abstract

Background & Objective: This study aimed to evaluate the effect of N-acetyl-L-leucine (NALL) supplementation on motor symptoms and quality of life (QOL) in patients with spinocerebellar ataxia (SCA). Due to the lack of effective treatments for this disorder and previous evidence suggesting potential neuroprotective effects of this compound, investigating its efficacy could be a crucial step toward improving clinical outcomes.
Methods: This study was a four-case experimental study with a cross-over design involving children with SCA. Patients were randomly assigned to one of two treatment sequences: the intervention-placebo sequence, or the placebo–intervention sequence. During the first phase, one group received NALL supplementation while the other received a placebo over four weeks. Following a four-week washout period, the treatment sequences were switched between the two groups. Patients were evaluated using standard measures including SARA, SCAFI, and the PedsQL QOL questionnaire at baseline and the end of each phase. A fasting blood sample was taken from all participants at each stage of the study. Additionally, adverse drug reactions were assessed after each intervention to monitor safety.
Results: Four girls with SCA, with an average age of 12.25±2.87 years, completed the study. The findings suggested improvements in the Total SARA Score, physical functioning as reported by the parents, and psychosocial health as reported by the child. The study showed that administering 2-4 grams of NALL per day over a four-week period to these patients did not result in any adverse effects.
Conclusion: Short-term NALL supplementation appeared safe and well tolerated in this small series. The trends towards improvement in certain measures, along with positive individual clinical responses, highlight the need for larger, longer-term, and more rigorously controlled trials.

Keywords

N-acetyl-L-leucine

Neurodegenerative disease

Motor symptoms

Quality of life

Spinocerebellar ataxia

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