CRG: Strengthening gene therapy for Huntington’s disease

CRG: Strengthening gene therapy for Huntington’s disease

News from CRG

A team led by Mark Isalan, former group leader at the CRG have engineered a therapeutic protein called a ‘zinc finger.’ Huntington’s disease is caused by a mutant form of a single gene called Huntingtin. The zinc finger protein works by targeting the mutant copies of the Huntingtin gene, repressing its ability to express and create harmful proteins.

In the new study involving mice, published in the journal Molecular Neurodegeneration, the injection of zinc finger repressed the mutant copies of the gene for at least six months. In a previous study in mice, the team had curbed the mutant gene’s activity for a few weeks, showing reversal of the bad symptoms in the diseased animals. By tweaking the ingredients of the zinc finger, in a new study they were able to extend its effects to several months, repressing the disease gene over that period without seeing any harmful side effects. This involved making the zinc finger as invisible to the immune system as possible.

The zinc finger protein sticks to the DNA of the mutant Huntingtin gene and turns off the gene’s expression. “We don’t know exactly how the mutant Huntingtin gene causes the disease, so the idea is that targeting the gene expression cuts off the problem at its source – preventing it from ever having the potential to act,” said Dr Isalan. By targeting the fundamental DNA of the gene, the zinc finger therapy also has the advantage over other potential Huntington’s therapies of needing less frequent treatments.

More information:
CRG Website

Reference article:
Carmen Agustín-Pavon, Michael Mielcarek, Mireia Garriga-Canut, and Mark Isalan. “Deimmunization for gene therapy: host matching of synthetic zinc finger constructs enables long-term mutant Huntingtin repression in mice” Molecular Neurodegeneration. 2016. DOI: 10.1186/s13024-016-0128-x