Study reveals drug used to treat epilepsy might be promising therapy for Machado-Joseph Disease

^{Translation by Diana Taborda}

A study carried out at the Centre for Neuroscience and Cell Biology of the University of Coimbra (CNC-UC) shows that carbamazepine, a drug used to treat epilepsy, could be a promising treatment for Machado-Joseph disease.

The work, which has already been published in the scientific journal Neuropathology and Applied Neurobiology, was coordinated by Luís Pereira de Almeida, Professor at the Faculty of Pharmacy of the UC (FFUC) and CNC-UC Principal Investigator, and Ana Ferreira, CNC-UC researcher.

Machado-Joseph disease, also known as spinocerebellar ataxia type 3, is an incurable, hereditary neurodegenerative disease caused by a gene mutation. The mutation leads to a defective form of the protein ataxin-3, which tends to clump together in the brain, causing neuronal dysfunction and death. The disease causes problems with walking, balance, speech, swallowing, eye movement and sleep.

Carbamazepine is an approved drug for other conditions, including epilepsy, so it can be used quickly to treat other conditions, which is an advantage. To find new pharmacological therapies for the treatment of Machado-Joseph disease, researchers tested the potential of this drug as an enhancer of autophagy (a process that eliminates abnormal proteins) using in vitro and in vivo models of the disease.

The team decided to test this drug after noticing "in previous research that the autophagy process is deregulated in Machado-Joseph disease, which means that the mutant protein is not properly eliminated. On the other hand, we observed that stimulating autophagy through a gene therapy strategy promoted neuroprotection in models of the disease," explains Ana Ferreira, first author of the scientific article.

Experiments on mice have shown that, after administration of carbamazepine, "the drug is capable of increasing autophagy and promoting the degradation of the mutant protein. In addition, the treatment reduced motor deficits and neuropathology in animal models of the disease," says the CNC researcher.

Besides Luís Pereira de Almeida and Ana Ferreira, the other participants in the study are Sara Carmo-Silva, José Miguel Codêsso, Patrick Silva and Clévio Nóbrega, also CNC researchers, Martinez and Marcondes França Jr., of the Neurology Department of the Faculty of Medical Sciences, State University of Campinas, Brazil.

According to the authors of the study, by showing that the drug carbamazepine may be useful in the treatment of Machado-Joseph disease and possibly other similar disorders, this study represents "a step forward in the search for an effective treatment for this neurodegenerative disease, although it is far from a cure".

The scientific article is available here.