We are fighting for treatment solutions that could help all affected patients. While severe phenotype-associated mutations may require gene therapy (strategies 1 and 3), milder phenotype-associated mutations could be treated with less invasive treatments options (strategy 2).

Strategy 1: Gene Replacement Therapy

  • Gene replacement therapy (GRT) is a one-time treatment that delivers a healthy copy of the gene to the
    cells with viral vectors.
  • The majority of patients with a CTNNB1 syndrome have one mutated gene that causes loss-of-function of
    the protein called beta-catenin.
  • Gene replacement therapy is a type of therapy where a functional copy of CTNNB1 is delivered to patient’s
    cells through adeno-associated virus (AAV) delivery.
  • Intended administration route is intrathecal administration.

Strategy 2: RNA-based Therapies

  • CTNNB1 Syndrome is an autosomal dominant condition. While one gene is mutated, the other one is healthy.
  • The RNA therapies would enhance the wild type β-catenin from the healthy CTNNB1 allele.
  • Inhibition of β-catenin degradation is currently explored by a) Skipping exon3 that encodes the regulatory region, b) Editing of β-catenin mRNA to mutate key phosphorylation residues that govern degradation, c) Downregulation of proteins involved in the β-catenin destruction complex.

Strategy 3: DNA-modification techniques

  • A “search and replace” gene editing method that can correct mutations in a precise way.
  • Our researchers will work on the development of prime editing variation for genome editing for delivery via viral or nonviral (RNP, RNA) delivery.
  • Currently, this is tested on a reporter and if successful on relevant cells harboring the specific CTNNB1 mutation.