Gene editing advancements could produce a future cure for Huntington's disease.
Huntington's disease, an inherited condition, causes the progressive degeneration of nerve cells in the brain. It affects an estimated 3 to 7 people of European ancestry per 100,000.
Symptoms progress slowly, normally starting in an individual's 30s or 40s; they include movement problems, such as jerking or writhing motions, and abnormal eye movements.
There are also cognitive symptoms, including problems organizing and focusing, and a lack of impulse control.
Huntington's disease is an autosomal dominant disorder, meaning it is caused by the inheritance of just one copy of a defective gene, rather than a pair. The gene in question is HTT, which codes for a protein called huntingtin.
Although the exact role of huntingtin is not known, it is presumed to be important for the function and development of neurons.
Gene editing and Huntington's disease
Currently, there is no cure for Huntington's disease. Available treatments only help the patient manage symptoms, addressing the cognitive, movement, and psychiatric symptoms separately. Research into specific treatments that might attack the root cause of Huntington's has not yet come up trumps.
Recently, a team from Emory University School of Medicine in Atlanta, GA, set out to disrupt the mutant HTT gene (mHTT) in a mouse model of Huntington's. They were led by senior author Dr. Xiao-Jiang Li, professor of human genetics at the university.
They used a Huntington's mouse model that has a human mHTT gene that replaces one of its normal HTT genes. Around the age of 9 months, motor problems are observed, alongside a buildup of mutant huntingtin protein in the brain.
In an attempt to treat the condition, the team used CRISPR/Cas9 gene editing; this is a process by which precise, targeted changes can be made to the DNA within living cells. They injected viral vectors carrying CRISPR/Cas9 into the striatum region of the mice's brains at the 9-month-mark. The striatum is an important part of the movement system.
Three weeks after the gene therapy, a "dramatic decrease" in mutant huntingtin was measured.
There were also improvements in grip strength, balance, and motor control. However, it is worth noting that the mice did not recover to a level where they performed as well as the control mice.
The scientists were surprised by the nerve cell's ability to heal themselves once the mutant protein had been removed.
Hopes for future treatments
For their study, Dr. Xiao-Jiang Li and his team used a so-called non-allele specific approach. In this technique, both the mutant and healthy genes are edited. This has the advantage that it does not need to be adjusted for each patient's genome; it is a one-size-fits-all approach.
Of course, this means that the healthy copies of the genes are also being pinpointed and destroyed, but previous studies have shown that mice older than 4 months do not need the HTT gene and can, therefore, do without it.
Although there is great hope attached to the potential of CRISPR/Cas9 gene editing, its safety and effectiveness need further testing before it can be rolled out to treat humans; playing with the DNA in brain cells is, of course, not without risk.
If this technique works in humans, it would be of huge significance. Rather than gene-silencing drugs, which would require ongoing treatment, gene editing would only, potentially, need to be given once, or infrequently.
There is still a long and winding road between this study and a viable treatment for Huntington's, but it is difficult not to feel heartened by the recent findings.