David Saperstein,4 Lisa L. Wei,5 Angelita Ray,5 Paul Kessler,5. Robert N. Frank,6 Peter A. Campochiaro.7. 1Casey Eye Institute, Portland, OR; 2Cullen Eye ...
NEURO GENE THERAPY II: NEW APPROACHES FOR DOMINANT, RECESSIVE, DEGENERATIVE AND AUTOIMMUNE DISEASES corrected the disease and prevented the subsequent neurodegeneration. The AAV2 treated brains were treated with a lower dose of vector than the AAV1 experimental group, and these brains have significantly lower levels of enzyme and vector transduction. Very few GUSB positive ganglion cells were detected in the retina, and low levels of GUSB activity was present in the gray matter of the spinal cord. Evaluation of disease correction in the eye, spinal cord and brain for the AAV2 treated brains is ongoing. These results suggest that fetal gene therapy with AAV vectors may provide a therapeutic strategy capable widespread enzyme distribution and disease correction in the CNS.
1064. AdPEDF Therapy for Subfoveal Choroidal Neovascularization (CNV): Preliminary Phase I Results Timothy Stout,1 Michael Klein,1 Eric Holz,2 Anurag Gupta,3 David Saperstein,4 Lisa L. Wei,5 Angelita Ray,5 Paul Kessler,5 Robert N. Frank,6 Peter A. Campochiaro.7 1 Casey Eye Institute, Portland, OR; 2Cullen Eye Institute, Houston, TX; 3Jules Stein Eye Institute, Los Angeles, CA; 4University of Washington, Seattle, WA; 5GenVec, Gaithersburg, MD; 6Kresge Eye Institute, Detroit, MI; 7Wilmer Eye Institute, Baltimore, MD. Neovascular age-related macular degeneration (AMD) is one of the leading causes of blindness, afflicting approximately 200,000 individuals/year in the United States. Pigment Epithelium-Derived Factor (PEDF), a naturally-occurring factor in the eye is a potent antiangiogenic factor. PEDF opposes not only VEGF but also other angiogenic stimuli such as FGF, PDGF and IL-8. In addition, PEDF is neuroprotective and thus may enhance preservation of retinal ganglion cells and photoreceptors that are essential for vision. To evaluate the safety and feasibility of intravitreal PEDF delivery via a second generation adenovector (AdPEDF) in patients with subfoveal CNV due to AMD, we conducted an open label, doseescalation protocol with 8 dose levels (106-109.5 pu in ½ log increments) in patients with active subfoveal CNV and best corrected visual acuity of 20/200 or worse in the study eye. After a single intravitreal injection of AdPEDF, 1 year follow-up consisted of periodic ocular exams, fluorescein angiograms, and laboratory evaluations including adenovirus neutralizing antibody titers and throat and urine cultures for adenovirus. Optical coherence tomography was performed as a substudy at 2 study sites. Six of 8 dose cohorts have been fully enrolled (n=18), and accrual is ongoing. Intravitreal AdPEDF has been well-tolerated and there have been no dose limiting toxicities or related severe adverse events. Three patients (two at 107.5 and one at 108.5 pu) had mild transient inflammation and Grade 1 elevation in intraocular pressure (IOP) thought to be probably or possibly related to the study drug. Neutralizing antibody titers did not increase at 3 months in 11 out of 12 patients and all adenoviral cultures were negative. Intravitreal injection of up to 108.5 pu of AdPEDF is well-tolerated and has not been associated with any serious short-term toxicity.
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Molecular Therapy Volume 9, Supplement 1, May 2004
Copyright The American Society of Gene Therapy
