Gene Therapy for Ataxia Teleangiectasia

Ataxia Telangiectasia (A-T) is a monogenetic, autosomal recessive disorder caused by mutations in the ataxia telangiectasia mutated (ATM) gene. Because the encoded Atm protein kinase plays a major role in DNA damage response, the absence of the Atm protein or functionality leads to a multi-organ manifestation. Progressive cerebellar degeneration, telangiectasia, immunodeficiency (impaired B- and T-cell development), radiation sensitivity and a predisposition to cancer are the most prominent clinical signs. The recurrent infections can cause lung damage and in the end also lung failure, which is together with cancer the main cause of death in A-T patients.

We aim to develop HSC-directed gene therapy for A-T using lentiviral gene transfer or gene editing in the ATM locus. The Atm knockout mouse mirrors the human disease phenotype well and will be used as preclinical model.

PhD students
Gilles Sartre
 

Scientific laboratory head
Prof. Ute Modlich