Friday, June 22, 2012
Meanwhile, stem cell clinical research for spinal cord trauma continues on several fronts. Our collective minds’ eye may think of stem cells as replacements for broken ones in the spinal cord. Most scientists I’ve talked to think stem cells will be more useful as chemical conditioners and stabilizers, not spare parts.
Here is a mid-year update.
California-based StemCells,. Inc. is still enrolling people three to 12 months post-injury, in Switzerland, to test purified human neural stem cells for safety and preliminary efficacy.
The company reports that is has dosed the first three patients all classified as ASIA A (no neurological function below the injury level). The second and third groups will be B and C, classifications, meaning less severe injuries. Not much news. Says the company:
Mechanism? Aileen Anderson, a scientist at UC Irvine whose preclinical work (the animals got good recovery) underpins the trial, noted in an earlier publication that “…following both sub-acute and early chronic transplantation we have shown that the predominant [stem cell] differentiation is oligodendroglial and survival of [stem cells] is required to sustain locomotor recovery, suggesting that oligodendrocytes integration with the host is likely a key mechanism of recovery.”
StemCells recently announced a Phase I/II clinical trial of the company’s human neural stem cell line for dry age-related macular degeneration. at the Retina Foundation of the Southwest’s Anderson Vision Research Center in Dallas.
Speaking of low vision, the only remaining embryonic stem cell trials listed on clincaltrials.gov are for macular degeneration and Staargards macular dystrophy. These are being conducted by Advanced Cell Technology, a California company, at UCLA and the Oregon Health and Sciences University in Portland. The company published preliminary data earlier this year. No bad news, and that’s good news. From the company:
Maryland-based Neuralstem continues its Phase I trials for spinal cord-derived neural stem cell transplants in people with ALS, at Emory University Hospital in Atlanta, Georgia. So far 16 patients have gotten the adult stem cells; one got two doses, in both upper and lower regions of the spinal cord. No reports of benefits (none anticipated) and no reports of adverse side effects.
Why this would be of interest to spinal cord injury community: It’s dealing with chronic, stable neurological damage.
CIRM: The California Institute for Regenerative Medicine (CIRM) continues to fund potential stem cell treatments. CIRM had fronted $25 million in the failed Geron trial (it was refunded) and there are many diseases being addressed in many projects. Here’s one related to SCI:
Zhigang He is the scientist who found a way to adjust the genetic programming of axons to permit them to grow in ways not seen before. By deleting the PTEN gene, axons of the cortical spinal cord moved well past the injury site. But the research is still figuring this out. So far, they don’t yet know how to make the regenerated axons functional, nor do they know how to dial down the gene in an animal that has already been injured. CIRM funded He’s group $5,609,890 to see if stem cells might be part of the solution.:
Recently published clinical results, from Korea: “Long-term Results of Spinal Cord Injury Therapy Using Mesenchymal Stem Cells (MSC) Derived From Bone Marrow in Humans.”
This group thinks MSCs may diminishing glial scars in human spinal cords, thus making regeneration easier. Too early to tell but this trial enrolled 10 people. Three, all cervical ASIA B injuries (some function below lesion) “showed continuous and gradual motor improvement in the upper extremities and significant MRI and electrophysiological changes during long-term follow-up.”
ReNeuron is a UK biotech that has transplanted neural stem cells into the brains of people who had ischemic strokes. From the company:
NEJM: “Clinical Implications of Basic Research: Stem Cells and Spinal Cord Repair,” a recent article in the New England Journal of Medicine by physician scientists Evan Snyder, from Sanford–Burnham Medical Research Institute, La Jolla, CA, and Yang Teng, Harvard Medical School.
Their goal was to coach clinicians on how challenging SCI research really is, especially for chronic SCI, characterized as the “third rail of neurorepair.” Here’s the set up:
Snyder and Teng are hopeful, and believe transplanted stem cells can be coaxed to fulfill “their fundamental teleologic role of maintaining homeostasis in a perturbed system.” The stem cell, they note, might be the “glue” that bonds many multidisciplinary approaches to spinal cord repair. They lay out a short case that rigorous science is still needed to safely move from lab to clinic, and they cite one recent set of stem cell studies as an example: stem cells from dental pulp (readily accessible from a living patient and immunologically matched) and reported recovery of function in animal models. The work comes from Japan, “Human Dental Pulp-Derived Stem Cells Promote Locomotor Recovery After Complete Transection of the Rat Spinal Cord by Multiple Neuro-regenerative Mechanisms.”
The study showed that human dental pulp (from baby teeth or adult third molars) improved rat SCI recovery three ways: preserving nerves and myelin; blocking inhibitory factors near the injury; and replacing lost cells. Said the authors, the dental pulp story highlights “that spinal cord injury is not a monolithic entity but rather a series of concurrent and interacting pathological processes; that multimodal actions will be required to combat the various facets of this malady…”
Snyder and Teng recapitulate what makes it so hard, and these are the take home lessons about current stem cell science:
….Substantial degrees of spontaneous recovery that are not related to treatment can occur for reasons not entirely known or controllable.
…The field itself is inherently vulnerable to observer bias because it lacks adequate varieties of truly objective, quantifiable, discrete measures of spinal function attributable purely to single pathways. Other confounders include related maladies (e.g., pain, bladder and bowel dysfunction, muscle atrophy, osteopenia, skin breakdown, and fatigue); the unmonitored effects of learning, environmental stimulation, motivation, and rehabilitation; the effect of immunosuppressant drugs or use of experimental animals with immunodeficiency; the sex and strain of experimental animals; and in stem-cell transplantation, the fusion of donor cells with host cells, leading to the mistaken identification of a host cell as having come from the graft.