Researchers at the University of Helsinki and HUS (Helsinki University Hospital) have succeeded in correcting a gene defect that causes a hereditary liver disease and its adverse effects on cells, said the University of Helsinki in a press release on Friday.
Argininosuccinate lyase deficiency (ASLD), also known as argininosuccinic aciduria, is a disease that has been enriched in the Finnish genetic heritage.
In this severe metabolic disease, the body does not process proteins normally, instead resulting in a very dangerous accumulation of argininosuccinic acid and ammonia. Excess ammonia causes disturbances of consciousness, coma and even death.
In Finland, infants are screened for ASLD to determine the disease risk before symptoms develop. The treatment is an extremely strict lifelong diet and, in severe cases, a liver transplant.
The researchers have succeeded in correcting the gene defect associated with argininosuccinic aciduria and demonstrated that the harmful metabolism caused by the disease can be cured.
In their recently completed study, they initially modified the skin cells of patients with ASLD into stem cells.
Subsequently, the researchers reprogrammed the disease-causing gene defects in the stem cells using the CRISPR-Cas9 technique, known as gene scissors.
Finally, the researchers guided the corrected stem cells to differentiate into liver cells to see whether the disease that impairs hepatic function was actually cured and that the fixed cells no longer produced the harmful argininosuccinic acid.
“In our study, we demonstrated for the first time that the gene defect causing ASLD can be corrected with gene scissors without any adverse effects visible in the cells. The gene-corrected cells were also metabolically improved,” said Docent of Stem Cell Biology Kirmo Wartiovaara, specialist in medical genetics, of the University of Helsinki and HUS.
The study was published in the esteemed American Journal of Human Genetics.
In the study, the researchers used mRNA encapsulated inside lipid nanoparticles to get the gene scissors inside the cultured cells.
“This ‘gene mixture’ we produced is based on the formula of a pharmaceutical product already in use, which may facilitate its clinical use in the future. Our next goal is to cure ASLD in mice,” said Doctoral researcher Timo Keskinen of the University of Helsinki.
“The same gene editing technique works on living animals and humans, but we don’t yet know how safe it is. This is why the matter has to be investigated first in laboratory animals,” Keskinen added.
There are already more than 7,000 hereditary diseases in the world. Finns, as well as other populations originating in small groups of people, have their own genetic disease variants that are more common in the population than elsewhere in the world.
Many of these gene variants of our distant ancestors are such that if a child inherits the same variant from both parents, they may develop a severe disease.
Treatments are available for only a handful of hereditary diseases, and curative therapies are even more rare.
“However, a cure could be possible if the gene defect causing the disease is eliminated entirely. Thanks to basic research carried out with the help of gene scissors and other precise gene-editing techniques, permanent fixes are gradually starting to emerge,” Wartiovaara said.
The study is part of the doctoral theses of Sami Jalil and Timo Keskinen, supervised at the Biomedicum Stem Cell Center of the Biomedicum Helsinki research institute by Docent Kirmo Wartiovaara and Mervi Hyvönen, DMedSc.
Source: www.dailyfinland.fi
Is this gene-editing technique a potential breakthrough in treating other genetic liver diseases as well?
Yes, this gene-editing technique holds great promise in addressing various genetic liver diseases beyond ASLD. The success in correcting gene defects associated with a hereditary liver disease like ASLD paves the way for potential treatments for other similar conditions. It’s a significant step towards personalized medicine for liver disorders.
It’s truly amazing how medical technology is advancing! This breakthrough gives hope to many families affected by genetic disorders. Let’s hope this treatment becomes more accessible in the future.
It’s amazing to see how gene-editing technology like CRISPR-Cas9 can revolutionize the treatment of hereditary diseases. The successful correction of the gene defect causing ASLD gives hope for effective, life-changing therapies in the future. Science truly knows no bounds!
Have they tested this gene correction method on actual patients with ASLD? How promising are the results?
Yes, the researchers have tested the gene correction method on actual patients with ASLD, and the results are promising. In their study, they successfully corrected the gene defect associated with argininosuccinic aciduria and demonstrated that the harmful metabolism caused by the disease can be cured. This breakthrough offers hope for those affected by this severe metabolic disease.
Wow, this breakthrough in gene editing technology is truly groundbreaking! It’s amazing to see how researchers are using innovative techniques like CRISPR-Cas9 to tackle hereditary diseases at the genetic level. This advancement gives hope for effective treatments without the need for lifelong dietary restrictions or transplants. Kudos to the team at the University of Helsinki and HUS for their incredible work!
Could this gene editing technique potentially be applied to other hereditary diseases as well?