Brain Regeneration usIng medical Devices, Gene vectors and stEm cells (BRIDGE)

Head: Gianvito Martino
Deputy head: Luigi Naldini

 

Vision

The characterization, dissection and experimental manipulation of the molecular and cellular events sustaining reactive brain repair might provide an attractive conceptual framework to foresee more efficacious therapies for neurological diseases. Indeed, fostering and/or resetting “spontaneous” neural tissue regenerative processes may lead to “natural” therapies characterized by higher efficacy and less toxicity. As a matter of fact, spontaneous neural tissue repair occurs in patients affected by inflammatory and degenerative disorders of the nervous system. However, this process is not robust enough to promote a functional and stable recovery of the 3D neural tissue architecture. The development of stem cell- and gene therapy-based approaches capable of promoting the restoration and/or regeneration of the diseased or injured nervous system is thus foreseeable.

Goals

Experimental strategies aiming at either replacing damaged vs. injured neural cells or delivering therapeutic genes have been developed in the last 30 years. However, most of these experimental approaches have failed to consistently foster repair in multifocal neurological diseases where the anatomical and functional damage is widespread. Novel stem cell- and gene therapy-based protocols might partially overcome some of these limitations, including:

  • the poor capability to grow and differentiate in vitro large number of neural cells from progenitors;
  • the anatomical, immunological and ethical barriers to cell transplantation into the CNS;
  • the limited bio-distribution of gene transfer products to the neural tissues;
  • the genotoxic and immunological risks associated with conventional cell and gene delivery approaches.

Novel therapeutic approaches that overcome these important hurdles might therefore represent valid alternatives for the treatment of multifocal nervous system diseases. These novel approaches may be complemented by the development of biocompatible medical devices providing the appropriate microenvironment to foster functional integration of the transplanted or endogenous gene-modified cells into the damaged tissues.

Main achievements (updated 2012)

The program has capitalized the scientific expertise and clinical excellence available at OSR in the areas of interest. Premiere knowledge derived from state-of-the-art stem cell and gene therapy experimental and human trials conducted in our Institute for a number of inflammatory and neurodegenerative conditions has been further expanded. New phase I/II human trials have been initiated in different myelin disorders, including multiple sclerosis and leukodystrophies, and new therapeutic preclinical strategies have been further developed in relevant animal model of neurodegenerative diseases. All of this work has been conducted with the main aim of combining powerful new stem cell isolation and gene transfer approaches to state-of-the-art neuroimaging, immunological and neurophysiological readouts. Finally, biological models has been developed to allow tracking gene expression and neural activity in the transplanted cells and the treated tissues.