Antiepileptic drugs are expected to treat hereditary ataxia
On February 11, a study published in the top international journal "National Science Review" found that valproic acid, an old anti-epileptic drug, has new functions.
This result comes from the research team of Professor Wang Xin from the State Key Laboratory of Cellular Stress of Xiamen University and the Institute of Neuroscience of Xiamen University School of Medicine. Researchers have confirmed through a series of studies that the clinical antiepileptic drug valproic acid can greatly improve a new type of The discovery of dysfunction and cerebellar atrophy disease has strong clinical translational application value and is expected to fill the gap in the treatment of hereditary ataxia.
There is no cure for hereditary ataxia
Ataxia is a type of neurological symptoms, the clinical manifestations are gait instability and loss of balance.
Among them, excessive drinking can cause symptoms of ataxia, which are acquired ataxia. Such conditions can generally be relieved or cured without treatment.
"The other big category belongs to hereditary ataxia, caused by congenital gene mutations, with different clinical manifestations, high mortality and disability rates, accounting for about 10%-15% of genetic diseases of the nervous system. There is currently no specific effect. Medicine, the treatment of this disease is still a problem in the world." Wang Xin introduced.
In 2015, the journal Nature Genetics reported a new type of hereditary ataxia "SCAR20", and Wang Xin is also the co-author of this article.
The family of the “SCAR20” case is mainly married with close relatives. The patient presents with early-onset cerebellar atrophy, severe motor imbalance and intellectual disability, unable to take care of himself, and life span is greatly shortened.
Due to the lack of specific medicines, clinicians are helpless.
To this end, in 2015, Wang Xin began to study "SCAR20".
Because patient samples are difficult to obtain, the research team first constructed a "SCAR20" model mouse. Behavioral analysis confirmed that the mice had progressive ataxia and cerebellar atrophy, which are very similar to clinical patients and suitable for follow-up mechanism and drug evaluation Research.
New use of old medicine restores nerve cell function
Through anatomy, the researchers confirmed that the massive death of Purkinje cells caused the patient's cerebellar atrophy and ataxia.
Purkinje cells are one of the largest neurons in the vertebrate brain. They are an important cell type that controls the coordination of body movements. Impaired functions often lead to ataxia.
So, how did Purkinje cells die?
"There are two factors that cause cell death, internal and external. Through in-depth research, we have found that the mitochondrial function in Purkinje cells has obvious defects." Wang Xin said that as the "energy factory" of cells, mitochondria are essential for maintaining cells. Survival is very important, once it is damaged, it will have a fatal blow to the cell.
In order to find drugs for the treatment of "SCAR20", the researchers used mouse models to screen several drugs with potential therapeutic effects in the clinic.
After many attempts, they found that valproic acid has a significant effect on "SCAR20" mice.
After the model mice were given valproic acid treatment for 1 month, the ataxia phenotype of the mice was greatly improved (the improvement rate was 74%), and Purkinje cell death was significantly suppressed (the suppression rate was 52%) , Neuroinflammation is significantly reduced, and mitochondrial transport and function are also restored to a certain extent.
"Encouraged by the good therapeutic effect of valproic acid on the'SCAR20' model mice, we are eager to bring it to the clinic as soon as possible, and realize the mission of valproic acid as an old drug and new use, so that patients with'SCAR20' can benefit soon." Xin Wang revealed that in the next step, the team will explore whether valproic acid is suitable for other types of hereditary ataxias, in order to clarify whether valproic acid has greater potential in the treatment of other types of ataxias.