SB-509

Zinc finger DNA-binding protein transcription factor activator VEGF-A upregulator treatment of amyotrophic lateral sclerosis treatment of diabetic neuropathy

M. Rendell

Research output: Contribution to journalArticle

Abstract

SB-509 is a zinc finger DNA-binding protein transcription factor (ZFP-TF) activator that upregulates the expression of vascular endothelial growth factor A (VEGF-A). VEGF-A plays an important role in both angiogenesis and neurological development. Independent research studies show that VEGF-A has direct neurotrophic activity on axonal outgrowth in in vitro culture conditions. The dual angiogenic and regenerative effects of VEGF-A on nerves suggest a potential therapeutic effect in neuropathic disorders. SB-509 stimulates endogenous VEGF-A expression, of all natural isoforms in their proper ratios. In the streptozotocin-induced diabetes model of neuropathy, SB-509 prevented the typical reduction in motor and sensory nerve conduction velocities. This favorable result led to human trials in diabetic neuropathy. A phase I trial showing trends for meaningful clinical improvement in SB-509-treated subjects led to a phase II trial. In the phase II trial, SB-509-treated subjects showed an increase of 55% in intraepidermal nerve fiber density (IENFD) compared to a decrease of 16% in placebo-treated subjects. Although there was no overall difference in clinical outcome measures between SB-509- and placebotreated subjects, subjects who started out with low IENFD showed clinical improvements correlating with increases in nerve fiber density. Additional clinical studies are in progress in diabetic neuropathy and amyotrophic lateral sclerosis (ALS). These studies have shown that plasmid-mediated delivery of the engineered zinc finger transcription factor is safe and may be a therapeutic option in a variety of diseases.

Original languageEnglish
Pages (from-to)585-588
Number of pages4
JournalDrugs of the Future
Volume36
Issue number8
DOIs
StatePublished - Aug 2011

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Diabetic Neuropathies
Zinc Fingers
Amyotrophic Lateral Sclerosis
DNA-Binding Proteins
Vascular Endothelial Growth Factor A
Transcription Factors
Nerve Fibers
Therapeutics
Experimental Diabetes Mellitus
Neural Conduction
Therapeutic Uses
Protein Isoforms
Plasmids
Up-Regulation
Placebos
Outcome Assessment (Health Care)
Research

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

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abstract = "SB-509 is a zinc finger DNA-binding protein transcription factor (ZFP-TF) activator that upregulates the expression of vascular endothelial growth factor A (VEGF-A). VEGF-A plays an important role in both angiogenesis and neurological development. Independent research studies show that VEGF-A has direct neurotrophic activity on axonal outgrowth in in vitro culture conditions. The dual angiogenic and regenerative effects of VEGF-A on nerves suggest a potential therapeutic effect in neuropathic disorders. SB-509 stimulates endogenous VEGF-A expression, of all natural isoforms in their proper ratios. In the streptozotocin-induced diabetes model of neuropathy, SB-509 prevented the typical reduction in motor and sensory nerve conduction velocities. This favorable result led to human trials in diabetic neuropathy. A phase I trial showing trends for meaningful clinical improvement in SB-509-treated subjects led to a phase II trial. In the phase II trial, SB-509-treated subjects showed an increase of 55{\%} in intraepidermal nerve fiber density (IENFD) compared to a decrease of 16{\%} in placebo-treated subjects. Although there was no overall difference in clinical outcome measures between SB-509- and placebotreated subjects, subjects who started out with low IENFD showed clinical improvements correlating with increases in nerve fiber density. Additional clinical studies are in progress in diabetic neuropathy and amyotrophic lateral sclerosis (ALS). These studies have shown that plasmid-mediated delivery of the engineered zinc finger transcription factor is safe and may be a therapeutic option in a variety of diseases.",
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