VEGF-B as a Therapeutic Agent for Neurodenerative Disease
Background:
The National Institutes of
Health's National Eye Institute is seeking statements of capability
or interest from parties to form a collaborative research alliance
to further develop VEGF-B as a Therapeutic Agent for
Neurodegenerative Disease.
Technology:
The biological functions of
vascular endothelial growth factor-B (VEGF-B) remain poorly
understood. Dr. Xuri Li and her colleagues at the National Eye
Institute have recently discovered that the protein is a potent
inhibitor of apoptosis, and unlike other VEGF proteins, is not
associated with undesired angiogenesis. The neuroprotective effects
of VEGF-B have potential applications in the treatment and
prevention of debilitating diseases including glaucoma, Alzheimer's
and Parkinson's diseases, retinitis pigmentosa, stroke, and brain
injury. It is estimated that glaucoma and RP strike, respectively,
2.2 million and 100,000 people each year in the United States.
Pre-clinical, In-vivo trials using a variety of mouse models
have validated the potential of VEGF-B as a therapeutic agent. In
an optic nerve crush (ONC) mouse model, an ocular disease that
induces apoptotic death of retinal ganglion cells (RGCs),
administration of VEGF-B was able to restore the number of RGCs by
1.7-fold while intravitreal treatment with VEGF-B neutralizing
antibody decreased the number of the viable RGCs by about 33%.
These results indicate that VEGF-B is critical to RGC survival in
the injured retina. Similarly, VEGF-B was able to inhibit
excitotoxin-induced apoptosis in the retina in an NMDA injury mouse
model.
Using a cerebral ischemic stroke model, it was shown that VEGF-B
expression is highly upregulated in the brain after stroke. VEGF-B
deficiency led to about 50% larger brain damage volume as compared
with that in wild-type mice. Despite upregulation of the protein in
wildtype mice, VEGF-B treatment still decreased the stroke volume
by about 32% and was able to protect neurons from
apoptosis.
Further R&D
Needed:
- Test the neuroprotective effect of VEGF-B in other animal
models, including, but not limited to, intraocular
hypertension-induced glaucoma, retinitis pigmentosa, Alzheimer's
disease, Parkinson's disease, etc.
- Test whether VEGF-B affects blood vessel morphology and
function in the neural system
- Examine VEGF-B gene and cell therapy using different viral and
non-viral vectors
R&D Status:
In vivo studies using VEGF-B as a therapeutic agent for several
diseases involving neural impairment have been conducted.
IP Status:
U.S. Provisional Application No. 60/972,780 filed 15 Sep 2007
Value Proposition:
- Potential to develop powerful therapeutic agents that can be
used to treat a variety of neurodegenerative diseases and ocular
degenerative diseases
- Ability to protect endangered neurons from death and avoid the
undesirable angiogenesis and increased blood vessel
permeability
Related
Publication(s):
Li, Y., Zhang, F., Nagai, N., Tang, Z., Zhang, S., Scotney, P., et
al. (2008). VEGF-B inhibits apoptosis via VEGFR-1-mediated
suppression of the expression of BH3-only protein genes in mice and
rats. Journal of Clinical Investigation, 118(3), 913-923.
Contact
Information:
Alan Hubbs, Ph.D., NCI Technology
Transfer Center
Phone: 301-594-4263
E-mail: hubbsa@mail.nih.gov
Reference: #636 AH
Updated 04/21/2008