According to BioSpace, recent research has demonstrated that CRISPR gene editing could be the answer to treating progeria, or Hutchinson-Gilford progeria syndrome. The Broad Institute and NIH have collaborated to investigate gene editing’s impact on the aging process, and their results have been published in Nature.
Progeria, which is also known as Hutchinson-Gilford progeria syndrome, is a very rare, fatal, pediatric, genetic disease that resembles premature aging. While children are born without any signs of the disease, the onset of symptoms begin at early infancy. This disease is caused by a mutation on the LMNA gene, which is essential for the protein of the membrane that surrounds the nucleus. Because of the deficiency of this protein, the nucleus becomes unstable. Premature aging comes from this instability of the nucleus. While progeria is a genetic disease, it is not usually inherited. Instead, it is the result of a random mutation.
The first symptoms that appear are a localized scleroderma-like skin condition and failure to thrive. After these symptoms appear, other physical abnormalities begin to appear, such as prominent eyes, a thin nose, a small chin, protruding ears, hair loss, wrinkled skin, joint issues, and weight loss. As a child ages they will experience the hardening of arteries, which then leads to severe heart problems. At two years old, the physical abnormalities begin to become noticeable, which is usually when the disease is diagnosed. Special imaging tests can also be ordered to further investigate cardiovascular issues or skeletal abnormalities. While there is a drug, lonafarnib, that has been shown to treat progeria, it is not FDA approved. Zokinvy has just recently been approved, making it the first treatment for progeria. Other treatment options are symptomatic.
CRISPR for Progeria
The director of the NIH, Francis Collins, worked with David Liu of the Broad Institute to conduct their research. They began their research with cells donated by progeria patients. Using a lentivirus to carry a T-to-C base editor, they were able to correct the DNA of 90% of the cells.
The next step was to test their work on mice. 62 mice were included in the experiment, one group was three days old and the other was 14 days old. For reference, 14 days for mice is comparable to five or six years for humans.
After being injected with the same base editor that the cells were, 10-60% of cells throughout the mice’s bodies were edited successfully. Not only was there change at a genetic level, but researchers observed improvements in physical appearance, mobility, and life span. Mice given the therapy lived for an average of 510 days, which can be compared to the average lifespan of 215 days in the control group.
While Liu and Collins acknowledge that more research needs to be done, the results of their work are very exciting. Liu also admits that more improvements must be made to his base editor. Regardless, their research could be the framework for future clinical trials.
They also recognize a recently approved treatment of progeria, Zokinvy. This drug is able to reduce the incidence of mortality by about 60% and increase lifespan by 2.5 years. Hopefully this therapy, along with Liu and Collin’s work, can bring more improvements for progeria patients.