Three stem cell stories.
Part I, from Switzerland. The StemCells, Inc. trial – 20 million human fetal neural stem cells injected in people four to eight months post spinal cord injury – reported that two of the first three patients enrolled got unexpected feeling returned below their injury sites.
All three tolerated the transplants with no adverse effects reported.
The safety trial is based on animal studies from the University of California, Irvine lab of
Aileen Anderson and her husband, Brian Cummings. The research team, which is not part of the trial, was very happy. “We were ecstatic,” Cummings told a reporter. Anderson, ever the careful scientist, cautioned that the sample is small and that more work must be done to verify the results. This phase of the trial is expected to include a total of 12 patients.
One of the trial participants has been identified. CNN reported that paraplegic Norwegian Knut Olstad, 46, injured a year ago in France, believes the stem cells have helped him regain sensation. "Sometimes, I can feel my girlfriend is squeezing my legs,” he said.
Sounds promising but this is very early, very raw data. “We have to put all the caveats on that,” Anderson said. “As scientists, that means we have to be cautious in interpreting what is here. It’s very promising, not definitive.” Still, she said, “seeing any sign of improvement is extremely promising, very surprising and very exciting.”
Said Armin Curt, M.D., the principal investigator for the trial at Balgrist University Hospital in Zurich:
"We are very intrigued to see that two of the three patients have gained considerable sensory function. The gains in sensation have evolved in a progressive pattern below the level of injury and are unanticipated in spinal cord injury patients with this severity of injury, suggesting that the neural stem cells are having a beneficial clinical effect. Sensory function of all these patients was stable before transplantation, so the reappearance of sensation is rather unexpected."
The sensory gains were first detected at three months post-transplant and have evolved at six months. " The company thinks there could be several reasons the stem cells improve sensitivity. They might restore myelin insulation to damaged nerves, thus improving the quality of signals to and from the brain. The cells could also nurture or replace existing nerves, or reducing inflammation that could block repair.
Stephen Huhn, M.D., head of the StemCells program:,
"To see this kind of change in patients who truly have the worst-of-the-worst type of injury to the spinal cord is very exciting. To our knowledge, this is the first time a sensory change of this magnitude has been reported in patients with complete spinal cord injury following a stem cell transplantation. We clearly need to collect more data to establish efficacy, but we are encouraged. We are pushing ahead with our trial and plan to dose the first patient with an incomplete injury soon."
Normally, early results are not reported in a a clinical trial ahead of running the full course of patients. StemCells, a publicly traded company based in California, is no doubt hoping this early data stokes enthusiasm for its own interests, and for the SCI stem cell field, deflated last year when Geron abandoned its embryonic stem trial for acute SCI. You’d think this sort of trial news might give the StemCells stock a little bump. Not so. Still trading at about $2 a share.
One more thing: If you believe you or a loved one may qualify for the study, contact the study nurse either by phone at +41 44 386 39 01 or by email at stemcells.pz@balgrist.ch.
Part II. “The magnitude of functional effect substantially exceeds those previously reported in studies of fetal or stem cell grafts to the injured spinal cord ...” That’s the bottom line in “
Long-Distance Growth and Connectivity of Neural Stem Cells after Severe Spinal Cord Injury,” published a few days ago in the journal
Cell.
For some reason, this paper, from a big-time research team and as bold and groundbreaking as it may seem, was mainly ignored by the mainstream science press. By comparison, the aforementioned StemCells, Inc. trial data got picked up much more widely. At any rate, the work comes from the Mark Tuszynski lab at the University of California, San Diego. In summary:
• Neural stem cells that express green florescent protein (GFP, for labeling) are able to grow axons over very long distances after severe spinal cord injury -- over a total of 17 spinal segments
• New synaptic relays are formed, improving electrophysiological and functional outcome
• Human neural stem cells exhibit similar growth properties as the rodent cells
• Grafted neurons overcome adult nervous system inhibition -- additional experimental manipulation of the inhibitory environment of the adult CNS is not required to achieve this long-distance regeneration
• No tumors
• Recutting the spinal cord immediately above the lesion site abolished hindlimb movement, indicating that functional recovery was dependent on inputs into the graft from the host.
Labs have been putting stem cells in spinal cord injured rodents for quite a while now – including one human fetal cell line in this study that’s been under investigation for many years. Why did the cells seem to grow and form connections so well, and bring on recovery of function, in this experiment? Might have to do with the delivery system, using a fibrin matrix as a scaffold, or the addition of a ten-molecule cocktail of growth factors. From the paper:
... early-stage neurons grafted in a fibrin matrix containing a growth factor cocktail extend large numbers of axons over long distances in the lesioned spinal cord and form neuronal relays that significantly improve electrophysiological and functional outcomes. The magnitude of functional effect substantially exceeds those previously reported in studies of fetal or stem cell grafts to the injured spinal cord, possibly due to enhanced graft survival generated by coimplantation with fibrin matrices containing growth factors.
“New connections grew in very large numbers and over very long distances after the most severe form of spinal cord injury,” said Mark Tuszynski, co-author of the study and director of the UCSD Center for Neural Repair. "We are conducting experiments now to determine whether this can be translated to humans."
The California Institute for Regenerative Medicine (CIRM), the agency that is distributing $3 billion in state funds for stem cell research (which gave
StemCells, Inc. $20 million) has awarded Tuszynski $4.7 million to further develop the advance, which he made with fellow UCSD neuroscientist Paul Lu.
"We further found that these stem cells send out new axons for truly remarkable distances in the spinal cord," Tuszynski said. "Previous work has shown axon growth of about two millimeters. Axons in this study grew more than 10 times longer than this. Previously, it had been thought that new axons cannot grow well in the injured spinal cord. This work shows that axons from these early stage neurons can grow remarkably well in the injured adult spinal cord."
Said Tuszynski, “These results suggest strong translational possibilities. Accordingly, we repeated these studies using cultured human neural stem cells.” The lab replicated the study using in two human stem cell lines, including one already being used in the ongoing Neuralstem human clinical trial for amyotrophic lateral sclerosis (ALS).
One other interesting aspect of the paper: Work in other labs has shown that a tumor suppressor gene called PTEN (short for ‘‘phosphatase and tensin homolog’’) is a major regulator of axon growth. Delete PTEN, cortical spinal axons regenerate at unprecedented rates. PTEN inhibits a molecular switch called mTOR (short for ‘‘mammalian target of rapamycin’’). The Tuszynski group reports here that mTOR contributed to the ability of axons in this study to grow into the adult injured nervous system. Sounds like a nice trail to follow, and indeed the UCSD team is pursuing a PTEN deletion model. Primate studies are also being planned to test the stem cell + fibrin matrix + growth factors.
Part III. File this is one in the sweet justice department. The stem cell predators got nailed and are headed for jail. Last year “
60 Minutes” did two segments on modern day snake oil salesman Larry Stowe and Frank Morales, who promised two men with ALS that their stem cell therapy would heal them. They were slippery and treacherous in the face of hidden cameras, but they didn’t get away with it. Last week, Stowe and Morales entered guilty pleas in a conspiracy to introduce misbranded and unapproved new drugs into interstate commerce. The FDA's Patrick J. Holland called the pleas "a victory for the American public." The case demonstrates "the FDA's commitment to investigating cases of individuals and business that prey on the sick and vulnerable with phony medical treatments."
Here’s one of the scams (from a U.S. Justice Department release; yuk, don’t try this at home):
Stowe further admitted that one of the unapproved drug products was a product called patient specific transfer factors. In order to produce this product, he obtained the services of a pathologist in Bryan/College Station, Texas. He then directed patients to send samples of their blood to the pathologist for the purpose of growing bacteria that would later be used to create the patient specific transfer factors. Stowe hired a laboratory in South Carolina to receive the bacteria which was then fed to chickens. The eggs produced by these chickens were later freeze dried and the powder from the eggs were placed in capsules and sold to patients.
