New findings may catalyze the development of drugs to treat Huntington's and other similar diseases, reports a study published online this week in Nature Biotechnology.
We all carry two slightly different copies of most of our genes. Huntington's disease, a severe neurological disorder, results when a sequence of three bases, CAG, in one of the two copies of the huntingtin (HTT) gene is repeated more than 36 times. The challenge in finding a cure is to silence the defective "stuttering" HTT without switching off the normal copy. So far, research into silencing mutant HTT relied on targeting specific mutations outside the repeats. But these strategies would not help patients with rare HTT mutations.
David Corey and colleagues show that an engineered RNA can discriminate between mutant and normal HTT on the basis of the repeated CAG sequence itself. They selectively target the mutant gene even in patient cells without the variants most commonly associated with Huntington's. Although more remains to be learned about the mechanisms involved and how well the treatment works in animals, the findings provide a new starting point for developing drugs that may eventually benefit all Huntington's patients.