Biology Reference
In-Depth Information
Nociception
Endomorphin-2 (40)
IL10 (61), TNF
Autoimmune diseases
EAE
IL4 (57)
IL1ra (37,58)
Brain tumours
Immune-modulators
IL2 (68), GM-CSF (69)
Connexin 43 (71)
Neuroprotection
Seizures
FGF2 + BDNF (36)
, (62,63)
GAD (65,66)
α
Disease models
Defective recombinant HSV-1 vectors
in Neurosciences
(reviews 32, 116)
Gene therapy trial
Cancer-related pain
Pre-proencephalin (41)
Fig. 5 Applications of defective recombinant vectors. The numbers in square brackets refer to the list of
references
12.1 Neuro-
protection
Many studies have been done to apply HSV-1 vectors expressing
trophic factors in animal models for neurodegenerative and neuro-
pathic diseases. Neuron proliferation or regeneration would be
important in the treatment of neurodegenerative diseases, such as
Parkinson and Alzheimer diseases [ 44 - 46 ], or of diseases associ-
ated to neurodegeneration (epilepsy, stroke, ischemic injury, and
spinal cord injury) [ 36 , 47 ]. Oligodendrocyte production would
be important in demyelinating disorders, such as multiple sclerosis
[ 37 , 48 ], or in the treatment of neuropathic pain. The neuro-
trophic factors (NTF) are peptides playing important roles, both in
the developing and in the adult brain. Alterations in NTF expres-
sion patterns in different physiopathological situations, as well as
effects of NTF in the adult brain (e.g., axonal sprouting induction
and neuroprotection), suggest their involvement in neuronal plas-
ticity [ 49 ]. Previous observations demonstrate that synergies occur
between NTFs and that it is possible to manipulate neural stem
cells (NSC) and to obtain neural progenitor proliferation, differen-
tiation, and migration, by using appropriate NTF combinations
[ 50 , 51 ]. The HSV-1 genome has the advantage of allowing the
insertion of large amounts of exogenous DNA, such as multiple
distinct transgene expression cassettes, therefore allowing to test
whether treatment with multiple NTFs can signifi cantly increase
neuronal survival in comparison with the delivery of single factors.
The therapeutic applicability of this system was proved in a model
of neuronal loss, the hippocampal sclerosis induced by pro-
longed generalized seizures. In this model, an epileptogenic insult
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