TNF CNS Gene Therapy

About us

image - Functional Genomics Group

from left to right: Georg von Jonquieres, Ziggy Harrison-Tikisci, Claudia Klugmann, Matthias Klugmann, Ben Rowlands, Dominik Fröhlich

The TNF CNS Gene Therapy Group is interested in the molecular mechanisms of normal and pathological functions of neurons and myelin-forming cells in the central nervous system. Our main focus is on a group of neurological disorders termed leukodystrophies. The word leukodystrophy is of Greek origin and translates into ‘leuko = white’, ‘dys = abnormal’ and ‘troph = growth’. Leukodystrophies are genetic diseases of the brain white matter associated with an early onset and substantial mortality in children. The population incidence is estimated to be one in 7,600 live births and to date there are no effective treatments available. Our aim is to establish gene therapy protocols for leukodystrophies and related neurological disorders.

The first step in understanding these devastating conditions is to establish accurate, rodent disease models, which enable us to study the underlying pathophysiology and to explore novel therapeutic approaches. Once established, we leverage these models to develop novel gene therapy strategies. We have a long-standing interest in adeno-associated virus (AAV) as gene therapy vectors and as tools in basic research.

We are developing the current AAV platform in two directions:

(i) to achieve widespread and stable gene expression in the CNS following intracranial or systemic delivery; and

(ii) to overcome the inherent neurotropism of AAV for targeting specific CNS cell populations including glia.

Our research group employs state-of-the-art techniques, including behavioural testing, neurogenetics, molecular biology, histology and neuroimaging to characterise disease models and to assess the therapeutic outcome of gene therapy.

Team

Collaborators

  • Caroline Rae, Neuroscience Research Australia (NeuRA), Australia
  • Beat Lutz, University Medical Center, University of Mainz, Germany
  • Miriam Schneider, Center for Mental Health, University of Heidelberg, Germany
  • Brad Alger, University of Maryland School of Medicine, Baltimore, Maryland, USA
  • Peter Kalivas, University of South Carolina, USA
  • Karen Szumlinski, University of Santa Barbara, USA
  • Sygnis Bioscience AG, Heidelberg, Germany
  • Giovanni Marsicano, INSERM Bordeaux, France

Grants & Funding

  • National Health & Medical Research Council (NHMRC) Project grant APP1050277 “Non-invasive gene delivery for expression of therapeutic genes in oligodendrocytes: A new strategy to treat myelin diseases.”
  • Mission Massimo Foundation Project grant: “Homing in on modeling and treating tRNA synthetase disorders.”
  • Gandel Philanthropy Project grant: “Gene therapy for DARS - a new childhood leuodystrophy.”
  • University of New South Wales (UNSW) Gold Star – NHMRC (Collaborative Grant with Prof. Caroline Rae): “Control of Brain Metabolism and activity by acetylation.”
  • Australian Research Council

Students

  • Ziggy Harrison-Tikisci (PhD)
  • Benjamin Rowlands (PhD)
  • Ms. Elizabeth Kalotay (PhD)