Key points:
- Scientists are developing messenger RNA (mRNA) therapies as an alternative solution for rare inherited metabolic diseases including argininosuccinic aciduria—a liver disorder that impacts the body’s ability to break down protein.
- By injecting mRNA therapy targeting liver cells in mice with argininosuccinic aciduria, the researchers corrected the lethal consequences of the disease.
- The team hopes to translate their mRNA therapy findings to humans with inherited liver diseases and other rare diseases in the near future.
A new study, published in Science Translational Medicine, reveals that messenger RNA (mRNA) can be used to correct a rare liver disease. By using a mouse model in combination with the technology used in COVID-19 vaccines, researchers have created an effective treatment that may have therapeutic use in people.
Previous gene therapy efforts used modified viruses to bring therapeutic genes to the disease cells. However, these viral systems caused severe adverse effects such as strong immune system reactions. Now, scientists are developing mRNA therapies as an alternative solution for rare inherited metabolic diseases including argininosuccinic aciduria—a liver disorder that impacts the body’s ability to break down protein.
In the current study, researchers protected the mRNA treatment in a microdroplet of lipids and injected it into mice to target their liver cells. The team tested the mRNA therapy on 31 mice at birth and at a late stage of disease in older mice that had argininosuccinic aciduria. They also used 31 untreated mice as their control group.
As it appeared that treatment benefits lasted around seven days, the team repeated the procedure weekly over the course of eight weeks. During the trial, researchers used positron emission tomography scans to track the correction of glutathione regulation and treatment success.
Researchers found that treatment corrected lethal consequences of argininosuccinic aciduria. All untreated mice died within the first two weeks of life, while the mice that received the mRNA treatment at birth survived for over three months. In the older mice, six of the seven who received treatment as a rescue therapy survived, while those left untreated died.
The team is looking to translate their findings to humans with rare diseases in the near future.
“We have shown that mRNA hold an unprecedented therapeutic potential for incurable genetic diseases, in particular liver conditions,” said study author Julien Baruteau of UCL Great Ormond Street Institute of Child Health. “We aim to apply this approach other inherited liver diseases and translate mRNA therapy to patients, especially in children.