CRISPR-Cas9 and Huntington’s Disease

By Evelyn Lee

January 9, 2023

UPDATED 12:00PM EST

[Photo credit: Alzheimer’s Association]

As biotechnology and medical advancements increase in affordability, accessibility, and efficiency, new novel treatments like CRISPR-Cas9 can help treat, slow down, or even prevent the progression of many genetic diseases. For example, a genetic disease known as Huntington’s disease has the potential to be mitigated thanks to CRISPR-Cas9 technology.

Huntington’s Disease is an autosomal - unrelated to one’s sex - dominant disease, which means that if an individual were to inherit one copy of the defective chromosome from either one of their parents, they would develop Huntington’s later in their life. Huntington’s is almost always fatal. People who suffer from it typically die from its symptoms, such as early-onset dementia, involuntary muscle movements and lack of coordination, and neurodegenerative decline. Usually, after the first onset of symptoms, the individual may only have 10 to 30 years left to live. An unusual trait of Huntington’s is that the severity and life expectancy after the initial onset of symptoms, may worsen with each generation. For instance, someone whose grandfather passed away from Huntington’s at the age of 70 and showed symptoms at 50 might show symptoms at 40 and pass away at 60. The reason for this stems from the genetic cause of Huntington’s.

Huntington’s Disease is the result of a mutated huntingtin gene (HTT). Huntingtin produces huntingtin protein, which is involved in chemical signaling in the nervous system. It is also characterized by the repeat of a CAG segment within the gene. This repeat typically occurs 10 to 30 times, but a mutated huntingtin gene might repeat the CAG up to 120 times. This disrupts normal nervous system function as the excess protein, or CAG, ‘clogs’ neurons. As this gene gets passed on, the number of CAG repeats destabilizes and ‘compacts’ onto itself, resulting in worsening symptoms as it gets passed on from generation to generation.

However, recent CRISPR-Cas9 research has shown promising results. For instance, some research involved the usage of specific allele CRISPR-Cas9 to precisely edit the CAG segment within the huntingtin gene, while other studies used the non-specific allele CRISPR-Cas9 to deactivate the huntingtin gene, alleviating test subjects’ symptoms. Another research team has even found a way to permanently deactivate the huntingtin gene, clearing protein clumps from animal and human subjects’ brains. Although much research remains, including investigating the long-term effects of using CRISPR-Cas9 on both adults and, potentially, children, it’s certainly promising for the thousands of Huntington’s patients in the US.

References

HTT Gene: MedlinePlus Genetics. medlineplus.gov/genetics/gene/htt.

“Huntington’s Disease: Genetics, Juvenile Cases and Chorea.” Cleveland Clinic, my.clevelandclinic.org/health/diseases/14369-huntingtons-disease.

Biswas, Tanuka. “CRISPR-Cas9 in Huntington’s Disease: Progress and Possibilities for Future Cure.” Synthego, 21 May 2021, www.synthego.com/blog/crispr-in-huntingtons-disease#huntingtons-disease-and-crispr-future-therapies-and-treatments. Accessed 20 Dec. 2022.