We took advantage of the fact that several cell lines display hypermethylation at the 1q21.1 locus (as annotated by ENCODE Roadmap, IHEC), mimicking methylation pattern in PPMS patients, and developed constructs expressing deactivated Cas9 fused to the catalytic domain of the demethylating enzyme TET1 (dCas9-TET1) to remove methylation from specific CpGs (see “Methods” section for further description). The gene discussed is TET1; the disease is primary progressive multiple sclerosis.