There are several studies to show the potential of N-Acetyl-DL Leucine in cerebellar ataxia. In one of them, the treatment improved ataxia in 12 patient’s type C disease. However, the effectiveness of N-Acetyl-Leucine is still controversial. Let’s look at its advantages and disadvantages.
Acryl-DL-Leucine is a branched-chain amino acid that is used to treat vestibular and motor symptoms of CA. Because it interacts with vestibular neurons, acetyl-DL-leucine can normalize the membrane potential of depolarized and hyperpolarized neurons. This amino acid also acts on the thalamus to regulate motor signaling. Despite its various advantages, acetyl-DL-leucine is not recommended for everyone.
Compared to l-leucine, N-acetyl-DL-leucine has similar physicochemical properties. It is soluble in water and has a high affinity for mitochondrial membranes. However, its incompatibility with other metabolites in the body means that it is not recommended for patients with renal failure or rheumatoid arthritis.
The first trial of acetyl-DL-leucine for cerebellar ataxia involved thirteen patients. The results of the trial showed that acetyl-dl-leucine improved motor function in patients with CA, compared to placebo. This study has many limitations. Moreover, no control group was used to determine the effects of acetyl-DL-leucine on cerebellar ataxia.
Its mechanism of action
The mechanisms of action of N-Acetyl DL-Leucine are not completely understood, but the dietary supplements is believed to act on cerebellar neurons. It is derived from the essential amino acid leucine. The N-Acetyl group is a chemical modification that can alter small molecules. Although this metabolite is similar to L-leucine, it has a therapeutic effect on postural compensation.
A study of mice with acute vestibulular vertigo found that N-Acetyl-DL-leucine improved visual acuity, contrast sensitivity, and visual field. The amine also reduced hyperpolarization and increased the production of the antioxidant nitrogen monoxide (NO). The molecule may also have a preventive and curative role in chronic diseases.
Increasing NO in the brain is a mechanism by which N-Acetyl-DL-leucine affects regional cerebral glucose metabolism. It also activates the citric acid cycle enzymes and controls ATP production. It may also affect the production of glutamate in the cerebellum, modulating the neurotransmission of this chemical. Molecular-level studies of this compound are still necessary to understand its exact role in the brain.
Its effect on vestibular neurons
Studies have shown that N-Acetyl-DL-leucine can affect the membrane potential of the vestibular neurons, which are important for balance. The substance works on both hyperpolarized and depolarized neurons to restore membrane potential to a normal value. It also restored membrane potential after unilateral labyrinthectomy in guinea pigs. These findings support its use as a treatment for acute vestibular syndrome.
Although N-Acetyl-DL-leucine has been used for decades to treat acute vertigo, there is no definitive evidence of a causal role for this amino acid. However, it has been shown to improve postural compensation in patients undergoing vestibular neurotomy and labyrinthectomy, as well as in a model of UL in mice. Although the exact mechanism of ADLL’s action is unclear, guinea pig studies indicate that ADLL can restore the normal activity of medial vestibular neurons.
The effects of N-Acetyl-DL-leucine on the cerebellum are largely unknown, but this substance has been shown to improve cerebellar symptoms in patients with lysosomal storage disease. Further research into this compound is necessary to determine whether it can benefit patients with lysosomal storage diseases. It is a good option for treating lysosomal storage disorders as it has been shown to be neuroprotective in a small number of patients.
Its efficacy in cerebellar ataxia
During the ALCAT trial, a drug containing N-Acetyl-DL-leucine was administered to a group of patients with cerebellar ataxia. In this clinical trial, N-Acetyl-DL-leucine was found to improve motor functions in patients with CA. The drug improved the symptoms of this disorder in both mice and rats. The drug showed superiority to placebo in the test of motor functions.
The drug’s effect on vestibular function was studied using patients with hereditary cerebellar ataxia. It normalized the membrane potential of vestibular neurons. It also improved postural compensation in patients with unilateral vestibulopathy. Acetyl-DL-leucine also restored membrane potential in vestibular neurons and increased the regional cerebral metabolic rate of glucose in the paraflocculus. It has been found to interact with phosphatinositol 4,5-bisphosphate, which influences ion channel activity.
The efficacy of N-Acetyl-DL-leucine in cerebellar ataxia was initially demonstrated in a study of 18 patients with degenerative CA. In this study, N-Acetyl-DL-leucine improved the coefficient of variation of stride time in 14/18 patients, while aminopyridines improved gait variability in a group of 18 patients with cerebellar ataxia. Both subjects’ subjective gait scores and the SARA score improved with treatment.