Improved Neurologic Exam and Nerve Conduction Velocities in Diabetic Neuropathy Patients Treated with Vascular Endothelial Growth Factor (VEGF) Zinc Finger Protein Activator (SB-509)
Abstract Number: 0008-OR
Authors: MARK S. KIPNES, MICHAEL MERREN, WARREN DOUGLAS, SCOTT HAMILTON, YA-LI LEE, KAYE SPRATT, DALE ANDO, San Antonio, TX, San Anselmo, CA, Richmond, CA
Results: Twenty-four patients were treated with escalating doses from one to sixty milligrams (mg) of SB-509, a plasmid DNA expressing a zinc finger transcription factor for VEGF, in a Phase 1a/b clinical trial. Treatment Plan 1 consisted of administration of SB-509 in one leg and placebo in the contralateral leg at dose levels of 1, 5, 10, 15 and 30 mg. Treatment Plan 2 consisted of administration in both legs with either SB-509 or placebo at dose levels of 30 mg and 60 mg. Three placebo patients and three SB-509 patients were treated at each dose level in Treatment Plan 2. Patients were evaluated using the Total Neuropathy Score (TNS), a composite scale incorporating symptoms, neurologic exam, and nerve testing, nerve conduction velocities (NCV), and quantitative sensory testing (QST). A statistically significant improvement in motor NCVs was seen at dose level 6 (60mg) at the six-month time-point when comparing the sum of all motor NCV (2 peroneal and 2 tibial NCV per patient) improvements from baseline to placebo. The mean value of improvement in the SB-509 group (three patients) was 3.934 M/Sec compared to -0.52 M/sec in the placebo group (six patients) ( p < 0.0383). QST testing at six months showed a 43% improvement in vibration units from baseline at dose level 6 in the SB-509 group compared to 20% worsening in the placebo group (p< 0.0058). The TNS at six months showed improvement in this scale with a mean score of 1.675 in the SB-509 group compared to a mean improvement of 0.665 in the placebo group at dose level 6. Improvements in NCV included three patients with unmeasurable NCVs who, after treatment with SB-509, NCV returned and improved over the six-month follow-up. The dose level of 60 mg showed consistent improvements in the neurologic exam, QST and motor NCV. These improvements in neurologic endpoints suggest that SB-509 has novel regenerative potential for the reversal of nerve damage in Diabetic Neuropathy. The 60 mg dose level has been expanded to accrue a total of 24 patients to further evaluate the long term effects of a single treatment of SB-509 and a Phase 2 trial in mild to moderate diabetic neuropathy has been initiated.