Curative
therapies still do not exist for most CNS diseases but gene therapy is a
promising new approach. We propose that it will be possible to modify brain
function and pathophysiology by targeted delivery of
specific curative factors to selected populations of brain cells that are
affected by disease. This opens the door for effective treatment regimes, which
can be tailored to individual patients needs. However, currently available gene
transfer vectors have limitations regarding safety and efficacy, as they do not
allow for targeting of specific populations of neurons or glia
or regulation of transgene expression.
The
NEUGENE consortium has been founded by leading European scientists from
academia and industry to overcome these limitations. The consortium will
develop Adeno-associated virus (AAV) and Lentivirus
(LV) - based tools for targeted and regulated gene transfer into different
populations of CNS cells. The consortium will provide a selection of vectors
that are optimized for different therapeutic approaches, e.g. regulated
expression of neurotrophic factors or manipulation of
neurotransmitter synthesis in specific neurons.
NEUGENE
has three major goals: 1) targeting gene transfer vectors to specific
populations of neurons and glia, by transcriptional
regulation and miRNA-mediated de-targeting and by
exploiting the cell-specific tropism of novel types of viral vectors, 2) tight
control over expression levels of therapeutic genes by using regulated systems
based on different principles, and 3) establishing the safety of the novel
vector tools.
NEUGENE will verify the
functional efficacy of the novel CNS gene transfer tools in a well-established
animal model of Parkinson's Disease (PD). This
disorder affects over 1.000.000 Europeans and is increasing in prevalence with
the aging population. Importantly, principles and mechanisms developed
and evaluated within the consortium will also be of direct relevance for gene
therapy of many other brain disorders.