Saturday, January 24, 2009

UPDATE: Those Wonderful Stem Cells Will Save Us

Gee guys I was only trying to be a smart ass this week, but just days after the MIC came on board, we see the first FDA approval of a phase-I clinical trial using actual human embryonic stem cells. Interesting timing by the Agency (only days after the MIC was sworn in; same week as the annual Right-to-Life march on DC, etc.). Simple coincidence? I think not. Five years from now, especially if they are proven to be safe and effective, I can guarantee you the MIC and other libtards will be claiming this as their own invention . Interesting how this new therapeutic was developed during the dreaded dark-age of the Bush years. So Ms Blumner, is this your idea of American science being in "suspended animation" and the Bush administration's "lack of interest in pushing America toward innovation"? Sounds like good old American ingenuity and free-market Pharma R&D to me. This is how American science works best; basic stem cell and development technology arising from Academia (Wisconsin and California in this case), and the IP being licensed by industry who then do the heavy lifting and run with it to market.

The company involved is Geron Corporation and the first indication is traumatic spinal cord injury. You can read the full press release here. GRNOPC1 is the therapeutic candidate and this cell product is a partially differentiated oligodendrocyte progenitor line arising from the human embryonic master cell stock H1 that was derived previous to August 9, 2001 and thus not subject to the Bush ban (although the company is quick to point out that no Federal funding was used in its derivation). These cells have "demonstrated remyelinating and nerve growth stimulating properties leading to restoration of function in animal models of acute spinal cord injury". Thus they will be tested in trauma victims by direct injection at the cord lesion site 7-14 days post injury. The primary end-point will be safety with a secondary endpoint of restored neurological function. So technically this is a phase-I/II clinical trial.

My big question from January 19 was whether anyone could show me the specs for a cGMP batch of stem cells. Apparently Geron could do that if we could get a peek at their 21,000 page IND application. Here is their abbreviated CMC description from the press release:

"GRNOPC1 is produced using current Good Manufacturing Practices (cGMP) in Geron's manufacturing facilities. Geron's GRNOPC1 production process and clean-room suites have been inspected and licensed by the state of California. The cells are derived from the H1 human embryonic stem cell line, which was created before August 9, 2001. Studies using this line qualify for U.S. federal research funding, although no federal funding was received for the development of the product or to support the clinical trial. Geron's H1 hESC master cell bank is fully qualified for human use and was shown to be karyotypically normal and free of measurable contaminants of human or animal origin. Production of GRNOPC1 from undifferentiated hESCs in the master cell bank uses qualified reagents and a standardized protocol developed at Geron over the past three years. Each manufacturing run of GRNOPC1 is subjected to standardized quality control testing to ensure viability, sterility and appropriate cellular composition before release for clinical use. GRNOPC1 product that has passed all such specifications and has been released is available for the approved clinical trial. The current production scale can supply product needs through pivotal clinical trials. The existing master cell bank could potentially supply sufficient starting material for GRNOPC1 to commercially supply the U.S. acute spinal cord injury market for more than 20 years. "

Pretty damn impressive. Now the big question will be safety and efficacy. Apparently this product is effective in animal models of spinal cord injury. How that will equate to human outcomes is the subject of the trial. Safety will be the primary issue. Stem cells are rapidly growing progenitor cells and thus possess a certain degree of cancer risk since they could potentially differentiate to a rogue cell type and form a tumor. That is how they were discovered in the first place as a cell type in teratomas. All indications in animals is that GRNOPC1 is low risk for this potential. But just as we have seen with conventional small-molecule therapeutics, issues of toxicity (or in this case tumor potential) may not become apparent until well after thousands of patients have been treated and followed up (classic post-market surveillance).

The other issue is rejection. These cells are allogeneic meaning that they came from a donor unrelated genetically to the recipient. As the press release points out, GRNOPC1 cells are not overly reactive immunologically but the clinical protocol does specify using "a limited course of low-dose immunosuppression". So they are not completely silent as far as the immune system is concerned. Whether long-term immunosupression will be required is unknown. Also, I have to wonder, what if there are long term immunological issues with these patients, will we see MS-type effects as demyelination progresses? Only time will tell.

And of course the big moral issue with this therapy surrounds the human embryo that was sacrificed for derivation of the original H1 cell line. Who was that? Who could they have been? Were they male or female (Geron knows this from the karyotype). The libtards will counter that it was just a small mass of cells (most likely a blastocyst phase embryo). The pro-lifers will tell you that it was human and sacred. Such things are best discussed with your God. I hear He is patient, but for those involved, I would have your speech rehearsed well in advance just in case.


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