Mapping the feasibility of allele-specific treatment in Huntington’s disease


  • Genotyping and targeting of specific alleles is feasible in Huntington’s disease (HD). This could allow for personalized treatment and preservation of the wild-type (wt) huntingtin (HTT) protein in heterozygous patients.

Why this matters

  • In most patients, HD is caused by heterozygous mutations in the HTT gene. The mutant HTT (mHTT) allele is abnormally expanded due to cytosine-adenine-guanine (CAG) repeats, but patients retain one wtHTT allele.

  • The wtHTT protein may be important for normal brain and neuroprotective functions and may offer advantages if preserved by allele-specific therapy.

  • Two nonpathogenic single-nucleotide polymorphisms (SNP1 and SNP2) have been reported in 65–70% of HD patients with European ancestry.

    • Heterozygosity for mHTT and SNP1, SNP2, or both, would allow for allele-specific treatment.

  • Mapping the genetic suitability of patients for allele-specific treatment will help to demonstrate whether this is a feasible therapeutic option.