A novel experimental gene therapy manages to combat Brugada syndrome, a dangerous heart disease

Brugada syndrome is a dangerous and life-threatening heart disease.

Currently there are no curative treatments and the options available are focused on

derived from it.

About 25% of these patients are identified by a

gene

.

Using this mutation as a target, a group of researchers led by Gang Yu has developed a

that has shown promising results in mouse models.

The results of this research have been published in the journal

and represent a first step towards the search for a curative treatment for Brugada syndrome, which would be a milestone for this pathology.

"It is certainly promising and could be

. It is not the solution for everyone, but if this can be tested in larger animal models comparable to the human heart, it could be considered." as a curative treatment", explains

, doctor and researcher at the Arrhythmia Unit of the Hospital Clínic i Provincial de Barcelona and the August Pi i Sunyer Biomedical Research Institute (IDIBAPS).

Developing a new mouse model

The research that Gang Yu has led first began with the creation of a mouse model for Brugada syndrome, a crucial first step for all of their subsequent work.

"It is a very interesting piece of work in this sense, since they have induced a mutation in one of the genes that encodes the sodium channel, which is partly responsible for Brugada syndrome. With this they have managed to

in mice", comments Andreu Porta-Sánchez.

In this way, for example, these mice had a higher incidence of arrhythmias, both ventricular and atrial, and also a higher incidence of

.

The model, however, is not perfect and some aspects of the disease have not been recapitulated as well as in humans.

"This may be inherent in the differences between the mouse heart and the human heart," adds Porta-Sánchez.

Overcoming the Pitfall of Too Large a Protein

Once the team of researchers already had the mouse model, the second part of the work consisted of developing the gene therapy that could combat the disease.

In this step, the team led by Gang You encountered the difficulty that the

sequence is

, as is usual in current gene therapies, and that it is responsible for introducing the protein that corrects the mutation. .

"What they have done to overcome this difficulty is to correct one of the components that is responsible for transporting this protein to the cell membrane. And, by achieving this, they have managed to improve the expression of normally functioning sodium channels on the cell membrane," adds the IDIBAPS researcher.

The team of researchers that has now published this study in

even proposes that this same technique could be used to

, although Porta-Sánchez considers that this is not so simple.

"It is not easy to find these diseases that have the same mechanism and it is not easy to find that key regulatory point that they have been fortunate to find in this case."

Next steps in the investigation

The results obtained have been very promising, and undoubtedly encourage further research in this direction.

The next step will be to obtain a model of a large mammal, which has its advantages but also drawbacks, as Porta-Sánchez explains very well.

"The advantage is that these hearts are fully comparable with humans. But the disadvantage is that gene therapy is in a phase of insufficient development, since the

-associated virus at present

. This is a step that is being attempted but is still in the development phase."

If all these obstacles can be overcome, in the future it would be possible for a percentage of patients with Brugada syndrome to finally have a

.

Nowadays these patients only have the option of an implantable defibrillator when they have a high risk of suffering sudden death or if they have suffered it and have recovered, there is also the option of drugs if this implant is not possible.

"In recent years, the possibility of rehabilitation with

has also appeared , but it is still a therapy that is not considered curative," adds Andreu Porta-Sánchez.

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