SB-509, an experimental drug to treat diabetic neuropathy, by Sangamo BioSciences is curently in human studies.
SB-509 is an injectable plasmid encoding a DNA-binding zinc finger DNA-binding protein (ZFP) transcription factor (ZFP TF) designed to upregulate the endogenous expression of the gene encoding vascular endothelial growth factor (VEGF-A).
VEGF-A has been demonstrated to have direct angiogenic, neurotrophic and neuroprotective properties. Data from Phase 1 and Phase 2 clinical trials in subjects with diabetic neuropathy (DN) have demonstrated a direct neuroregenerative effect of SB-509 treatment.
IENFD is a validated, direct histologic measurement of small unmyelinated sensory nerve fibers in the skin, the primary sensory nerves involved in diabetic neuropathy.
IENFD also correlates with neuropathy severity in diabetes, nerve fiber densities derived from sural nerve biopsies and levels of vascular endothelial growth factor-A (VEGF-A). In subjects with more severe neuropathy, as judged by their baseline IENFD, a greater nerve regrowth response to SB-509 treatment was observed compared to regrowth responses in placebo-treated subjects.
Sangamo’s double blind, repeat-dosing, placebo controlled Phase 2b study, SB-509-901, is designed to finalize dose, schedule and primary and secondary endpoints for pivotal Phase 3 trials.
SB-509 trial will involve a total of 150 subjects who will be randomized 1:1 between placebo and treatment groups.
“The body of clinical data obtained in previous trials of SB-509 has enabled us to design a very focused Phase 2b study that will accrue subjects that we believe are most likely to show a significant response to SB-509 over the 180 day test period,” commented Dale Ando, Sangamo’s chief medical officer and vice president of therapeutics, in a press release.
The data generated to date also demonstrated that SB-509 treatment resulted in statistically significant increases in nerve fiber density, nerve regeneration and an improvement in clinical outcomes such as NIS-LL and sNCV, he said.
Diabetic neuropathy is a progressive degenerative disease that is one of the most frequent complications of diabetes, affecting between 14 and 16.5 million Americans in 2007.
High blood glucose levels lead to nerve damage over time, primarily affecting peripheral nerves. Symptoms include numbness, tingling sensations and pain particularly in the toes or feet, which gradually evolve to loss of sensation and motor function as nerve damage progresses.
Ulcers and sores may appear on numb areas of the foot as pressure wounds or injuries go unnoticed. Despite palliative treatment, these areas of trauma frequently become infected and this infection may spread to the bone, necessitating amputation of the leg or foot.
More than 60 percent of non-traumatic lower-limb amputations in the United States occur among people with diabetes. In 2004, this translated to approximately 71,000 amputations. The Centers for Disease Control estimates that from 1980 through 2007, the number of Americans with diabetes increased from 5.6 million to 23.6 million and that of those about 60 percent to 70 percent have mild to severe forms of neuropathy.
Sangamo BioSciences, Inc. is focused on the research and development of novel DNA-binding proteins for therapeutic gene regulation and modification.
The most advanced ZFP Therapeutic development program is currently in Phase 2 clinical trials for evaluation of safety and clinical effect in patients with diabetic neuropathy and ALS.
Sangamo also has two Phase 1 clinical trials to evaluate safety and clinical effect of a ZFP Therapeutic for the treatment of HIV/AIDS. Other therapeutic development programs are focused on cancer, neuropathic pain, nerve regeneration, Parkinson’s disease and monogenic diseases.
Sangamo’s has developed a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs).
By engineering ZFPs that recognize a specific DNA sequence Sangamo has created ZFP transcription factors (ZFP TF) that can control gene expression and, consequently, cell function.
Sangamo is also developing sequence-specific ZFP Nucleases (ZFN) for gene modification. Sangamo has established strategic partnerships with companies in non-therapeutic applications of its technology including Dow AgroSciences and Sigma-Aldrich Corporation.