Huntington’s disease mutation in mice corrected using stem cells
Scientists have moved a step closer to using a patient’s own cells to treat Huntington’s disease, a fatal genetic disorder. The mutation that causes the disease was corrected in a patient’s skin cells before they were transformed into stem cells used to treat a mouse model of the disease.
Huntington’s disease is caused by a repeating DNA sequence in the Huntingtin gene. People with less than 36 repeats of the C-A-G genetic sequence do not suffer the condition, but those with 36 or more will. The more repeats a person has the earlier in their life they will develop symptoms; the average age to start showing signs of the disease is about 40 years old. The mutant gene encodes a faulty protein that kills neurons in the brain. Symptoms vary in their severity from mild mobility problems to advanced dementia and eventually death.
The research team used a method called homologous recombination to replace the faulty gene in skin cells taken from a patient, with a normal gene containing approximately 20 C-A-G repeats. They then used an established technique to turn the corrected skin cells into induced pluripotent stem cells (iPSCs), which behave like embryonic stem cells and are able to differentiate into any type of cell. These were then injected into the brains of mice genetically engineered to possess the faulty Huntingtin gene. The iPSCs became established in the brain and formed neurons in the area of the brain that is damaged by Huntington’s disease.
The research did not cure the mice of the disease but did show that cells can be modified and then used as a treatment. Such an approach of using a patient’s own cells avoids many complications of immune-rejection and the moral concerns surrounding embryonic stem cells. But much more work is needed before this treatment can become a reality.