Test gene therapy in Huntington's disease

07-31-2019

Claudio Hetz and René Vidal used a method that replaces drugs in mice.

In Claudio Hetz's imagination, gene therapy is the simile of a vehicle that transports the essential merchandise to survive. "It is avant-garde, well emerging. Instead of using a pill with a chemical compound, a gene is used as a therapeutic agent," explains the director of the Millennium Institute of Biomedical Neuroscience of the Faculty of Medicine of the University of Chile.

The doctor of Biomedical Sciences uses this technique in a specific place in the brain. In simple, it introduces a gene wrapped in a virus, which is responsible for infecting damaged neurons. "Think of a capsule drug. In this case, the capsule is the virus. Instead of being synthetic it is biological. And the medicine is the gene. It is not a virus that makes you sick, it is a kind of vehicle that injects sick cells the therapeutic gene, "he describes.

Avant-garde therapy

Hetz and the doctor in Molecular and Cellular Biology Rene Vidal in Chile patented gene therapy against Huntington's disease in mice. That means that they are the creators of the method that prevents the disease from moving forward, for now, in those afflicted animals.

"It is a neurodegenerative and hereditary disease. It affects the striatum area of ​​the brain, which is where the neurons that modulate movement are," says Vidal.

The genetic cause, says the researcher at the Universidad Mayor, is the mutation of a gene called huntingtin that occurs before birth. This alteration causes, over time, the death of the group of neurons that inhabit the striatum.

"In general, clinical symptoms appear at 50 years. But there are cases of motor disorders at 20 years of age. That depends on how aggressive is the mutation. The disease causes loss of movement, uncontrolled motor activity and cognitive impairment," Vidal details.

Specifically, the mutated gene affects neurons because it generates toxic proteins that live inside that type of cell. That, says Vidal, prevents neurons from functioning well. "They die finally. An excessive accumulation of toxic proteins occurs," he laments.

Hetz explains that patients with Huntington, a product of the genetic mutation, have another altered biological aspect: an insulin cousin, known as the growth factor IGF2, which is responsible for protecting neurons from death.

"Cells, in this case neurons, need them to sustain their life, reproduce. That is why they are called growth factors. We discover that if one introduces the IGF2 gene, Huntington's symptoms can be reduced in animals. We can also lower the amount of that toxic mutant protein that Huntington produces, "celebrates Hetz.

To introduce that gene and prevent the disease from progressing, the researchers used gene therapy. The gene, Hetz explains, was manufactured, that is, their DNA letters linked them accordingly. That gene, he says, was introduced into a virus. "They are tiny viruses, they measure nanometers. They are parasites of other viruses, so they don't make us sick." Hetz describes.

That virus with the gene inside, he adds, is put inside a pin needle, almost the diameter of a hair and injected into the striatum. "The mice improved their motor skills by 50 percent and we also prevented the disease from progressing," he concludes.

More accurate than drugs.

María Soledad Matus, a researcher at the Science and Life Foundation, says that gene therapy has had good results. "It is interesting for pathologies that have no cure and that affect the central nervous system, since it is difficult for drugs to access the affected place and be precise. They do not have the property of accessing the central nervous system. They have benefits that are lacking in drugs, "says the doctor in Cellular and Molecular Biology.

Huntington is a genetic disease in which proteins accumulate. "It also occurs in other diseases. When characteristics behave, it is possible that a strategy that serves one disease serves another," he explains.

Hetz complements that there are currently gene therapies approved by the United States Food and Drug Administration. "Two against cancer and one against blindness."