Levacetylleucine, sold under the brand name Aqneursa, is an FDA-approved treatment for Niemann-Pick disease type C (NPC). It is an oral medicine, approved by the FDA in September 2024, later approved in the European Union in January 2026. Its exact mechanism of action remains unclear, but it is believed to restore energy dysregulation in the cerebellum. This is what relieves neurological symptoms present in NPC. Levacetylleucine is also in Phase III clinical trial for Ataxia-Telangiectasia (A-T) and is being studied for the treatment of other diseases. This includes GM2 gangliosidoses, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS).
How does it work?
Levacetylleucine is also called N-acetyl-L-leucine (NALL). It is a modified form of the amino acid leucine. Amino acids are the building blocks of proteins. Leucine is classified as an essential amino acid because your body cannot produce it, but it can be obtained from food sources.
There are several proposed mechanisms of action of NALL. The N-acetylation modification of leucine allows it to bypass the blood-brain barrier and enter the cells more easily compared to leucine. Once inside the cells, NALL then reacts with proteins in the cell to become leucine, which promotes energy production.
NALL itself also has other functions inside the cell. A pre-print study published on bioRxiv (bio archive) demonstrated that NALL can influence the localization of gene regulators essential for the lysosomal and autophagic pathways. These are the systems responsible for disposing and recycling waste. In disease models of NPC, they also found that NALL treatment restores lysosomal and autophagic dysfunctions present in the disease.
Levacetylleucine in disease treatment
The use of Levacetylleucine in disease treatment started in France in the 1950s for acute vertigo under the trade name Tanganil™. However, Tanganil™ contains a mixture of NALL and N-acetyl-D-leucine (NADL), which differs slightly in their structure. In 2013, a landmark case study conducted by Strupp and colleagues found that off-label use of the drug improved gait and motor symptoms in patients with various forms of cerebellar ataxia. This soon led to the evaluation of this drug in Niemann-Pick disease type C (NPC).
NPC is a rare progressive inherited disorder. It is characterized by the inability of the body to transport lipids inside the cell, resulting in their build up within body tissue and subsequent tissue damage. There are significant variations in the clinical presentation of the disease, but the most prominent neurological hallmark is cerebellar ataxia. In 2015, a clinical study conducted by Bremova and colleagues tested the efficacy of the drug on NPC patients, and found that it showed significant improvements in the SARA scores and 9-Hole Peg Test. Other studies have also found that NALL specifically is the driver of symptom improvement, not NADL. Therefore, future drug development efforts were focused on NALL alone instead of the mixture.
A clinical trial was then conducted in pediatric and adult NPC patients and NALL treatment resulted in a significant reduction in disease progression, which led to its FDA approval (Aqneursa). An extended study also showed that the treatment resulted in long-term neuroprotection in the patients, not just a temporary improvement in disease symptoms. Aqneursa is also in Phase III clinical trials for Ataxia-Telangiectasia (AT), where it has met all primary and key secondary endpoints. The FDA has granted the drug priority review and assigned a PDUFA date of September 19th, 2026, positioning it to become the first-ever treatment for both adult and pediatric AT.
Research studies are currently evaluating the efficacy of NALL in other neurological conditions, including Parkinson Disease, Ataxia-Telangiectasia, and GM2 Gangliosidoses. Future research will be critical to further defining its mechanism of action, confirming its long-term safety and utility, and determining its therapeutic potential across a broader range of neurodegenerative disorders.
If you would like to learn more about Levacetylleucine, take a look at this article from NeurologyLive.
Snapshot Written by:Christina Peng, PhD
Edited by: Celeste Suart, PhD
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