Rare diseases can be treated with gene therapies – 04/06/2024 – Health

The ability to make specific modifications to the human genome has been a target of medicine since the discovery of DNA as the basic unit of heredity in 1869.

And what was once the subject of fiction is increasingly a reality today. Through so-called gene therapy, it is now possible to cause changes in the DNA of cells affected by certain diseases and activate the body’s defenses with the aim of recognizing damaged tissue and promoting its elimination.

In Brazil, there are currently six medicines approved by the Anvisa agency (National Health Surveillance Agency), with gene therapy being possible in the treatment of hereditary retinal diseases, considered rare, for SMA (spinal muscular atrophy) and in the treatment of hematological cancers. —originated in the blood.

Today, there are more than 16 medicines approved worldwide and the expectation is that, by 2030, there will be more than 60 new products of this type.

A sign of the viability of applying gene therapy is the increasing investment that biotechnology companies are making in the development and submission of product release applications.

As an example, the medical director of Pfizer Brazil, Adriana Ribeiro, says that the company is working on infusion gene therapy (medicines directly into the bloodstream) for illnesses such as hemophilia type A, hemophilia type B and Duchenne muscular dystrophy (DMD), a neurological disease.

“We are in the last phase of studies, so it is a very close reality,” says the director.

Gene therapy emerged with the purpose of acting on monogenic diseases, that is, diseases caused by mutations that affect a single gene. However, there are already several studies that use the technique in complex and multifactorial diseases, such as hereditary and rare diseases, which can be caused by the mutation of a single gene; multifactorial diseases, which have multiple genes affected, such as Parkinson’s; and cancers, such as in editing for CAR-T cell treatment.

It is estimated that there are at least 13 million Brazilians living with a rare disease – which, together, totals more than 7,000 illnesses.

For most of them there is still no approved specific treatment and, since 80% of rare diseases are of genetic origin, gene therapies can play a fundamental role in the area, says Ribeiro.

How it works

Gene therapy is the treatment of diseases through modifications in the genetic material of cells. With this technique, it is possible, for example, to place functional genes in cells that have defective genes.

According to the specialist, there are two ways to carry out the therapy: taking the patient’s cells and modifying them to be able to recognize a cancer cell, for example; and through a vector, —normally a virus with no further potential for infection— that functions as a means of transporting already corrected genes to the cell.

The long-term effects of the treatments are not yet known, so it is difficult to talk about a cure, explains Gustavo Campana, specialist in clinical pathology and laboratory medicine at FMUSP (USP Faculty of Medicine) and medical director of the DB Diagnósticos network.

“It will depend on the type of disease. Gene therapy may be your first treatment option or it may be a refractory treatment option to improve the patient’s quality of life and increase life expectancy”, says Campana.

To undergo treatment, a person living with a genetic disease for which gene therapy is available must undergo a medical evaluation, and the form of treatment depends on each case. Among the factors that the health professional will be able to evaluate are the patient’s age and the existence of antibodies previously formed against viral vectors.

First of all, the diagnosis

A key point that experts say is as important as therapies are genetic tests, as they not only carry out the diagnosis, but also assess predispositions and risks.

“The time between suspicion and diagnosis is sometimes very long,” says Campana, “and you have some gene therapies, for example, that are recommended for patients up to six months of age.”

An American study carried out by the National Organization for Rare Disorders found that only 36% of patients were diagnosed in the first year, and 28% of them reported a delay of seven years or more in starting treatment.

“In Brazil there is already a name for this, which is the ‘diagnostic odyssey’. Once we have a treatment available, it can no longer take so long for a diagnosis”, explains Michele Migliavacca, a medical geneticist accredited at Omint.

In the doctors’ view, in addition to diagnoses, the next step for medicine will be in the assessment and proposition of risks, mainly for polygenic diseases, such as diabetes.

“This should enter clinical practice soon, using what we call precision medicine, which is nothing more than the combination of clinical epidemiological data with genetic data”, says Campana.