excerpt from new TSC (Feurstein) story..
"...Sangamo BioSciences (SGMO) has a neat story to tell: The company is engineering protein "switches" called zinc fingers that can turn genes on or off.
Zinc finger proteins are found naturally in the body, where they regulate the function of genes. Sangamo is engineering unique zinc finger proteins that attach to, and regulate, specific genes for therapeutic effect. The idea, for instance, would be to create a zinc finger protein that turns off a disease-causing gene; or conversely, turns on a gene known to have a therapeutic benefit for patients.
The theory behind zinc finger protein therapeutics -- as Sangamo calls them -- is similar to the work being done with RNA interference, or RNAi. The big difference, however, is that RNAi can only turn genes off, while zinc finger proteins have the ability to turn genes on and off.
It's definitely cool stuff, but does it work? Sangamo's lead effort is centered on patients with diabetic neuropathy -- nerve damage that causes numbness and pain in the legs and arms of diabetes patients.
Sangamo's drug SB-509 is a zinc finger protein encoded to turn on, or upregulate, the VEGF-A gene. VEGF-A is known to have a positive effect on nerve cells, either by protecting existing nerve cells or encouraging new nerve cell growth.
A small phase I study of SB-509 in diabetic neuropathy patients showed some promising results earlier this year. This has led Sangamo to start a larger phase II study. Patient enrollment should be completed by the end of the year, with data available in the second half of 2008.
Astute followers of biotech may remember that VEGF is best known not as a protein that acts as nerve-cell promoter, but one that stimulates the growth of new blood vessels. Genentech's (DNA) blockbuster cancer drug Avastin is an inhibitor of VEGF, which means it blocks the production of new blood vessels, thereby starving cancerous tumors of the nourishment they need to grow and survive.
So, if SB-509 turns on the VEGF-A gene, is there a risk that patients get too much VEGF in their body, and therefore run the risk of encouraging the growth of cancerous tumors?
Theoretically, this is a safety risk with the SB-509 program, says Sangamo CEO Ed Lamphier. But he says testing so far has found that there isn't any measurable increase in systemic levels of VEGF in patients given SB-509, nor has an increased cancer risk been reported in patients or animals.
That said, Sangamo is excluding patients with a history of cancer from the current SB-509 clinical studies. Lamphier is downplaying the potential cancer risk of SB-509, but that exclusion suggests it's a potential worry for the company and the FDA.
(One more thing: If there's no measureable increase in VEGF in patients, does this mean SB-509 isn't having the predicted mechanistic effect on the VEGF gene? It's a question the phase II study should answer.)
A lot of companies are working in the RNAi field, bringing a surge of deal-making with Big Pharma. Sangamo, however, has the world of zinc finger protein drugs largely to itself. Whether or not that's a good thing won't be known until we get more clinical data...." |
