Spotlight on Research - Spinal Cord Injury and Stem Cells

The Advocate is the official publication of the Spinal Injuries Association


I wrote following article for the Spotlight on Research section of the November-December edition.


In early October, Geron Corporation, a biotech firm in California, hit the headlines with news it had enrolled the first patient in a clinical trial of human stem cells to treat spinal cord injury. The trial would use embryonic stem cell derived oligodendrocyte progenitor cells known as GRNOPC1(we’ll explain exactly what that means shortly).


Geron’s President and CEO Thomas Okarma said the trial aimed to shift the outcome for a person with spinal cord injury “from one of no hope for any recovery to an outcome much like the incomplete patients who can respond to physical therapy.” Mr Okarma described the GRNOPC1 clinical trial as ‘a milestone for the field of human embryonic stem cell-based therapies.’

People with spinal cord injuries are used to hearing impressive promises – what is the real story?

First - what are GRNOPC1 cells? The key terms here to extract from the headlines are: derived and oligodendrocyte. The trial does not, as sometimes reported, inject embryonic stem cells into the damaged cord; nor will the injected stem cells transform into new neurons (nerve cells). Instead, human embryonic stem cells will be cultured in the laboratory in a chemical environment that will see them become progentior cells – cells that are programmed to become oligodendrocyte cells. It is these cells that will then be injected into the damaged cord.

So what are oligodendrocyte cells? In the undamaged spinal cord, mature oligodendrocytes wrap themselves around the axons of neurons and insulate the electrical signal passing along the axon, in much the same way that plastic coating insulates electrical wiring. When a spinal cord injury causes neurons to die or be damaged, the oligodendrocytes may also die, leaving the surviving neurons without insulation (a process known as demyelination) hence slowing or stopping the signals passing up and down the spinal cord. Replacing the oligodendrocytes with GRNOPC1 cells is the aim of Geron’s trial.
The GRNOPCI trial originates from research published in the Journal of Neuroscience in 2005 by Hans Keirstead and his team at the Reeve-Irvine Research Centre in California. When Keirstead injected oligodendrocyte progenitors into rats with spinal cord injury, the rats went on to recover locomotor function. At the microscopic level, Keirstead saw that the oligodendrocytes remyelinated the surviving axons – that is, the insulation around the neurons came back, but only in those rats that were treated within the first few days following injury. Keirstead thinks that the injected oligodendrocytes may also release chemical factors that support the neurons that survive the initial injury.

So, what about the person about to receive the treatment? At this stage, little is known about the patient in the Geron trial though we do know that they must have sustained a complete thoracic spinal cord injury no more than 14 days before beginning treatment.

The patient was enrolled at the Shepherd Centre in Atlanta in the US, a spinal cord injury and traumatic brain injury rehabilitation centre that provides a continuum of care from intensive care through to outpatient support and is actively involved in spinal cord injury clinical research.

As this is a phase-1 clinical trial, the aim is to assess whether the procedure is safe rather than effective, but the trial will also assess whether the patients show improved neuromuscular control or sensation in the trunk and legs. It is anticipated that, in time, a total of 10 patients will be injected with GRNOPC1 at various centres across the US.

Once its deemed to be safe, Geron plans to extend the study to increase the dose of GRNOPC1, enrol patients with complete cervical injuries and patients with incomplete injuries.

Despite the work done in rat models of spinal cord injury, some are concerned that the reality for humans may not live up to the hype. One of the main arguments is that there has been little clinical demonstration that human embryonic stem cells are safe to inject into the damaged spinal cord, primarily because one of their defining traits is the development of teratomas – a type of benign tumour. It was this safety concern, and the report that rats developed microscopic cysts at the injection site, that put Geron’s human trial on hold last year.

In defence, Keirstead argued: “This trial was approved only after rigorous safety testing and consultation of countless experts in the field.” Indeed, approval for the trial was only granted after six years and the submission of 28,000 pages of supporting data. “Any benefit to the patient, even an incremental one, would be a resounding victory … this is the first step along a road that we’re soon going to see turn into a racetrack,” said Keirstead.

Others are not so effusive, including Dr David van Gend from the lobby group Australians for Ethical Stem Cell Research who recently told the Sydney Morning Herald that Geron must be “hoping like hell the mature stem cells don’t regress into embryonic stem cells and cause tumours”.
But many in the research world remain cautiously optimistic: “We hope the treatment will prove to be safe and really wish that it will show some benefit, as indicated by the preceding experiments in animals,” says Professor Robin Lovell Badge, Head of Genetics at the MRC’s National Institute of Medical Research in the UK.

“The trial has been set up to look for problems and, if these arise, then hopefully those involved will at least learn how to do better next time.

“The first attempts at heart transplants did not go at all well, but now they are an accepted part of clinical treatment.”