The brain edition is “getting closer to reality”: the tools of genetic alteration that are facing deadly diseases. Impressive results in rats open the way to advances in genetic edition for neurological diseases.
Scientists are increasingly close to applying the genome editing to a new formidable target: the human brain.
Over the past two years, a series of technological advances and promising results in rats have been launching the bases to treat devastating brain diseases through techniques derived from genetic edition CRISPR -CAS9.
Researchers believe that humans’ rehearsals could be just a few years away.
“The data never seemed so good,” he says Monica Coenraadsfounder and executive director of Rett Syndrome Research Trust in Trumbull, Connecticut, to the magazine. “This is less and less science fiction and more and more reality.”
A scary challenge
Researchers have already developed genetic editing therapies to treat blood, liver and eyes disease. In May, an extraordinary success was reported by using personalized genetic editing therapy to treat a baby named KJ Muldoon, who.
But The brain puts special challenges. The molecular components used to treat KJ were inserted into fat particles that naturally accumulate in the liver.
Now, scientists are looking for similar particles who can selectively direct the brain, protected by a defensive barrier that prevents many substances from entering.
Although KJ’s story is exciting, it is also frustrating for families of people with neurological diseases, Coenraads explains, whose organization is dedicated to Rett síndromea rare disease that affects brain development.
“The question I hear from our families is: ‘It was made so quickly to him. Why is it for us to take so long?'”, it says.
This group of worried families is growing, as doctors and family members turn more and more genomic dryness to find the causes of brain disease until recently mysterious, says Cathleen LutzGeneticist of The Jackson Laboratory, in Bar Harbor, Maine.
“People are starting to find that, for example, their child’s seizures are related to specific genetic mutations,” he explains.
Cut and sew
Mice studies suggest that genetic editing technology, which can rewrite small excerpts from the genome From a cell, it is ready to correct some of these mutations.
In July, investigators reported having repaired mutations that, in humans, cause a disease called Alternating Hemiplegia of Childhood (AHC). The condition, which usually arises before 18 months of age, causes seizures, learning difficulties and episodes of partial paralysis.
“It’s a horrible disease”, David Liuchemical biologist at the Broad Institute of Mit and Harvard in Cambridge, Massachusetts.
Liu and their team applied in rats with a AHC Causing Mutation a derivative version of CRISPR called prime editing. The technique corrected the mutation in about half of the cerebral cortex, a region responsible for learning and memory.
Rats also showed improvements in many aspects: less serious seizures, better cognitive and motor performance, and greater life expectancy. “The results in the rats were impressive”Says Liu.” We were surprised. “
Liu’s laboratory also works in rats to correct mutations responsible for two other neurological diseases in humans: Huntington’s disease and the Atachia of Friedreich.
Already at Shanghai Jiao Tong University School of Medicine, China, neuroscientist Zilong Qiu and his team used base editing To correct a mutation in the gene MEF2C. In children, this mutation can cause Epilepsy, intellectual deficit and difficulties in speech.
In male rats, the same mutation Changes social behavior between pairs. The correction of mutation in MEF2C through base editing – An ultra -précisis version of CRISPR that corrects individual DNA letters – restored normal social behaviors and improved the links between nerve cells.
Qiu and Liu also work independently in genetic editing therapies to treat Rett syndrome, usually caused by mutations in the gene
MECP2.
A genetic editing approach is particularly important in this case, underlines coenraads: simply Add an extra and normal copy From the MECP2 gene, as conventional genetic therapy would do, it can lead to that cells produce excess protein. High levels of this protein can be toxic.
But the genetic edition would only allow to correct the natural copy of the genereducing the risk of excessive MECP2 production, explains Qiu.
Financial obstacles
The path between results in rats and clinical trials in humans is long.
Qiu expects your team to be ready, within five years, to test a base editing in people with Rett syndrome. And Liu’s team believes that in the coming years, it will be able to complete the studies necessary for Advance to humans com AHC.
Since fat particles used in the treatment of kJ are not yet an option, both teams anticipate that clinical trials will use a virus called AAV9 (adeno-associated virus 9) to transport the genetic editing components to the brain. This virus can infect brain cells and partially cross the hematoencephalic barrier.
However, AAV9 implies risksbecause high doses can trigger fatal immune responses. Researchers are running against time to develop improved versions that can be administered at lower doses.
Coenraad organization also finances efforts to develop methods without using viruses that can deliver molecules to brain cells.
At the end, The biggest obstacle may not be technological. In the United States, the biotechnology industry is going through a prolonged financial crisis. Some investors have moved away from genetic therapies and genetic edition, expensive and difficult to produce. “Funding is running out,” says Coenraads, who seeks to remain optimistic.
“Things work like a pendulum,” he concludes. “For now, I think we have to keep your head down and continue to produce good data”.
