FDA-Approved Compound Shows Promise in Parkinson’s Disease Treatment

Northwestern Medicine scientists have identified an FDA-approved compound, N-acetyl-L-leucine (NALL), that demonstrates neuroprotective effects in experimental models of Parkinson’s disease. The findings, published in The Journal of Clinical Investigation, suggest a potential latest therapeutic avenue for the disease.

How NALL Works

NALL appears to target multiple molecular pathways crucial to the development of Parkinson’s disease within dopaminergic neurons. Researchers found that NALL enhances the clearance of a toxic protein called alpha-synuclein by boosting the HTRA1 enzyme, which breaks down protein aggregates. NALL restores dopamine function by increasing levels of parkin, a protein that improves synaptic vesicle recycling and dopamine signaling [1].

Previous Approvals and Safety Profile

NALL is a derivative of the branched-chain amino acid leucine. It has been used for decades outside of the United States to treat acute vertigo and vestibular disorders, conditions causing dizziness and balance issues. In 2024, the FDA approved NALL for the treatment of Niemann-Pick disease type C1, a rare genetic disorder that affects the nervous system and organs [1]. This prior approval supports the compound’s safety profile in humans.

Research Findings

The research involved generating dopaminergic neurons from patients with both familial and sporadic forms of Parkinson’s disease. Treatment with NALL led to positive changes in these neurons. Further validation was conducted using mouse models of Parkinson’s disease, where oral administration of NALL decreased alpha-synuclein pathology and improved dopamine-dependent motor learning [2].

Potential for Broader Impact

Researchers believe NALL’s effects may extend beyond Parkinson’s disease. The ability to target alpha-synuclein pathology and improve synaptic function suggests potential benefits for other neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia [1].

Next Steps

Future research will focus on understanding how NALL induces HTRA1 expression and whether it impacts mTOR signaling or leucine-sensing pathways. Clinical trials will be necessary to determine the optimal dosage of NALL, assess its disease-modifying potential, and evaluate its effectiveness in the early or prodromal stages of Parkinson’s disease [1].

Reference: Song P, Chen C, Franchini R, et al. N-acetyl-L-leucine lowers α-synuclein levels and improves synaptic function in Parkinson’s disease models. J Clin Investig. 2026;136(5):e196137. Doi: 10.1172/JCI196137