The latest news and information about what's going on with SCI science and research. Brought to you by Sam Maddox, author of the Christopher & Dana Reeve Foundation Paralysis Resource Guide.

Stem Cells Improve Fine Hand Control


StemCells Inc. released some early data a few days ago from its Pathway stem cell clinical trial for chronic cervical spinal cord injury. You have to be a little careful when public companies release information about their work – investor enthusiasm is really the point. But these unpublished results appear to be quite remarkable: Five of six motor complete quads treated long after their injuries with stem cells recovered strength in their hands. Four got better dexterity and fine motor control in their hands and fingers.
 
Anecdotally, a company spokesman who was pressed for detail during an investor conference call (if you have 38 minutes to burn, it has been archived), noted that three treated patients were able to pick up a key, put it in the lock and turn it 90 degrees. That's impressive.
 
As regular readers know, we have been following StemCells Inc.'s work for many years here. The preclinical basis for the study came from the University of California, Irvine labs of Aileen Anderson and Brian Cummings. Anderson leads a lab that is part of the Reeve Foundation's International Consortium on Spinal Cord Injury.
 
The company first tested the safety of its cell line in 12 patients with complete thoracic spinal cord injuries, mainly in Zurich. Patients were injected with adult neural stem cells above and below their lesion site. The company reported the cells were safe and that seven of 12 had sensory gains that would not have occurred spontaneously.
 
Because some biological activity apparently occurred, with no adverse effects, that was a big deal. But thoracic recovery doesn't matter much, and isn't going to stoke either investors or patients. The company determined that testing the cells in cervical injuries was the way forward. At least if there is even only a small segmental recovery, it might still be meaningful.
 
So, late last year, the company launched Pathway.
 
The trial is already recruiting patients in its second phase. It is controlled and randomized and will include 40 patients with C5 – C7 injuries (incomplete) between four and 24 months post injury. The company said last week that this cohort has already been one-third enrolled, at 12 centers in the U.S. and Canada. Each patient who gets cells gets 40 million of them. The controls, used for comparison, get no cells, just standard care.
 
Regarding the latest data, StemCells Inc. chief medical officer Stephen Huhn described two systems used to measuring strength and recovery before and after cell transplantation – the International Standards for Neurological Classification of SCI (ISNCSCI) and GRASSP, which stands of Graded Assessment of Strength, Sensitivity and Prehension.
 
ISNCSCI measures five key muscles, two in the hand, three in the arm. GRASSP measures ten muscles, six in the hand and four in the arm, and evaluates actual functions, such as pouring water, opening a jar, threading a nut on a bolt, picking up a coin, etc.
 
So, a caller asks, can you be more clear on what was recovered. Said Huhn, "... we have three patients who pre-transplant were unable to pick up a key and insert it into a slot — after transplant they were able to pick up the key and insert it into the lock and turn it at the full 90 degrees ..."
 
From a company press release:
  • Additional highlights of the six-month interim results include:
  • Muscle strength was improved in five of the six patients.
  • Four of the five patients with gains in muscle strength also demonstrated improved performance on functional tasks assessing dexterity and fine motor skills. 
  • Four of the six patients had improvement in the spinal level of injury as defined by the ISNCSCI assessment; three upgraded one level and one upgraded two levels.
  • Based on a Patient Global Impression of Change (PGIC) assessment, four of the six patients reported that their condition had improved post-transplant.
  • Changes in muscle strength and function were observed around three months post-transplant, consistent with the onset of sensory improvements seen in the Company's Phase I/II thoracic study.
  • No adverse events were attributed to the cells.
  • The timing of the transplants ranged from ten to 23 months post-injury.
Said Huhn:
The improvements in upper extremity muscle strength and function can be seen in specific tasks such as opening a jar, picking up coins or grasping and turning a key. Gaining the ability to perform these simple tasks should result in more independence and an improved quality of life for those impacted by spinal cord injuries. These findings demonstrate the ability of our HuCNS-SC® cells to improve both muscle strength and motor function, thereby changing the trajectory of recovery following a spinal cord injury.

Other SCI Stem Cell News
The oligodendrocyte progenitor cells trial (formerly known as the Geron trial) marches on. Asterias Biotherapeutics concluded recruitment of a safety cohort for a dose-escalation clinical trial of this embryonic stem cell line, this time looking at complete cervical subacutes, between 14 and 30 days post injury. Three patients were administered a low dose of 2 million cells. Safety seems fine; no serious adverse events observed. The company says one of the three patients went from ASIA A to ASIA C, that's a meaningful gain in function. Next phase of cervical study: five patients will get 10 million cells.

Neuralstem SCI trial
In July, Neuralstem completed its Phase I safety trial of its neural stem cell line in four patients with chronic spinal cord injury at the University of California, San Diego School of Medicine. In October, the company reported that implantation of stem cells in  spinal cord injury patients has been safe and well tolerated. Patients in the trial received six injections in, or around, the injury site.
 
Another acute study, in animals
A recent paper from the Jerry Silver lab at Case Western in Cleveland, in collaboration with the biotech company Athersys: "Stem cell treatment mediates immune response to spinal cord injury in pre-clinical trials."

From Athersys:
Here we show that a single intravenous dose of human multipotent adult progenitor cells (MAPCs) delivered one day following contusive SCI remarkably improves both locomotor and urinary functions. Interestingly, MAPCs rarely enter the nervous system, however, a significant increase of white matter sparing and a marked change in macrophage/microglia activation is observed in the spinal cord. This study highlights the promise of therapies directed at altering the peripheral response to immune-mediated CNS pathologies and establishes human MAPCs as a novel therapy for the treatment of acute SCI.
 
 
Posted by Sam Maddox on Nov 24, 2015 3:41 PM America/New_York

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