Study in Monkeys Identifies Ambroxol as Possible Therapy for Gaucher Disease

Study in Monkeys Identifies Ambroxol as Possible Therapy for Gaucher Disease

Researchers suggest that a compound called ambroxol should be explored in clinical trials as a potential drug for Gaucher disease. Their study in non-human primates showed that the drug increased the activity of brain glucocerebrosidase — the enzyme lacking in this disease.

Since patients with Parkinson’s disease might also have mutations in the gene encoding glucocerebrosidase, they could also benefit from such a treatment.

The study, “Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate,” was published in the journal Synapse.

The research team at University College London in the U.K. had previously studied ambroxol in mice. Using normal mice and mouse models of Gaucher and Parkinson’s disease, they showed that the compound entered the brain of the animals, and increased the activity of glucocerebrosidase.

In mice with high levels of human alpha-synuclein (a protein involved in Parkinson’s), ambroxol reduced the levels of the protein. This is an important finding, since people with Gaucher disease have a 20 to 30 times higher risk of developing Parkinson’s disease.

But since mice are quite different from humans, the research team tested the compound on non-human primates to gather more information to support a future clinical trial.

For their work, they used three adult, healthy Cynomolgus monkeys that received daily treatment with ambroxol or a control substance for 28 days. The team compared two different doses of ambroxol.

The higher dose, 100 mg of the compound, increased the activity of glucocerebrosidase in several brain regions between 16% and 24%. In the cerebellum, however, only a 5% increase was seen. The lower dose (22.5 mg) did not lead to increased enzyme activity.

The team also noted that the activity of HEXB — another lysosomal enzyme — was increased, with the magnitude of the increase mirroring the regional patterns seen for glucocerebrosidase. The researchers argue that this would suggest that ambroxol might also have an effect on lysosomal content. Lysosomes are organelles found in the cells of humans and animals that break down molecules and participate in other cell processes.

Of note, the observation that ambroxol increased the activity of HEXB differs from studies in mice, suggesting that the compound might act differently in primates.

While researchers underscored that the data is preliminary, with observations from only three animals, they believe the study supports the idea of testing ambroxol in a human clinical trial.

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Magdalena is a writer with a passion for bridging the gap between the people performing research, and those who want or need to understand it. She writes about medical science and drug discovery. She holds an MS in Pharmaceutical Bioscience and a PhD — spanning the fields of psychiatry, immunology, and neuropharmacology — from Karolinska Institutet in Sweden.

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