RO7812653

**RO7812653** is an investigational antisense oligonucleotide (ASO) developed by Roche for the treatment of early symptomatic Alzheimer's disease (eAD), including mild cognitive impairment due to AD and probable AD dementia. Administered intrathecally, it selectively targets all variants of the apolipoprotein E (APOE) mRNA transcript, inducing its degradation via Ribonuclease H mediation to reduce APOE protein expression in the central nervous system (CNS). APOE, particularly the ε4 allele, is a major genetic risk factor for Alzheimer's disease, and lowering its levels is hypothesized to mitigate amyloid pathology and neurodegeneration. Currently in a Phase 1 first-in-human trial (NCT07234942, BP45770), evaluating safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity following single ascending doses.