Zinc finger ligand SB-509 for diabetic neuropathy

The pharmaceutical company Sangamo BioSciences Inc announced to start a new phase IIb study. This to analyze the efficacy and safety of their new compound, SB-509. This is a ligand for the so-called zinc finger proteins, for moderate to severe diabetic neuropathy.

Their press release (January 2009)

60433966-Robertprzybysz-Dreamstime-INP Zinc finger ligandSangamo develops DNA-binding “zinc finger” proteins to modify and regulate genes. SB-509 is a zinc finger activator of vascular endothelial growth factor, which has been shown to promote the survival and development of nerve cells.

“This puts us in a position to the risk the program significantly,” Chief Executive Edward Lanphier told Reuters in a telephone interview on Friday.
He said Sangamo is “in active discussions” with potential partners. And the new trial “lets the pharma world know in no uncertain terms that we are going to push this drug forward.”

Lanphier said the SB-509 trial will involve patients with moderately severe. Rather than mild, neuropathy — the group shown to benefit most from the drug in earlier trials.

The zinc finger DNA-binding protein, which may activate the DNA to create certain proteins, has great potential.[R = 16298089] The zinc finger protein that VEGF-A (vascular endothelial growth factor) activates is SB-509. VEGF-A promotes the formation of blood vessels, nerve growth, and is protective for the nerves.[1][2]

Sangamo is currently (2010) recruiting patients for a Phase I clinical trial in diabetic neuropathy. A Phase I trial is used to test an experimental drug for the first time in humans to evaluate the drug’s safety, or to identify side effects, and to establish the maximum tolerated dose.

Information related to this trial

SB-509 contains the gene, or DNA code, to specify a protein. When SB-509 is injected into the leg, the drug enters the muscle and nerve cells around the injection site and causes these cells to make a protein.

This protein causes the cells to increase the production of another protein called Vascular Endothelial Growth Factor (VEGF), which may improve the structure and function of nerves. This increase in VEGF may protect and repair the damage caused to nerves by diabetic neuropathy.

Jan M. Keppel Hesselink, MD, PhD, march 2010
‘Zinc finger ligand SB-509 for diabetic neuropathy’

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[1] Rebar EJ. | Development of pro-angiogenic engineered transcription factors for the treatment of cardiovascular disease. | Expert Opin Investig Drugs. | 2004 Jul;13(7):829-39.

[2] Liu Y, Figley S, Spratt SK, Lee G, Ando D, Surosky R, Fehlings MG. | An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury. | Neurobiol Dis. | 2010 Feb;37(2):384-93. Epub 2009 Oct 29.

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