Special delivery: Getting stem cells into the spinal cord

By Katie Moisse

Day two of the World Stem Cell Summit featured a much-anticipated update on a groundbreaking clinical trial launched in January to assess the safety and feasibility of injecting fetal stem cells into the spinal cords of people with Amyotrophic Lateral Sclerosis (ALS).

To describe injecting a million cells into the precise area of the spinal cord that is home to the motor neurons degenerating in people with ALS as “tricky” would be somewhat of an understatement. For starters, the spinal cord is buried in a thick, boney spinal column tucked under layers of muscle. And just when you think it’s uncovered, a tough, blood vessel-laden membrane called the dura makes one final, stingy stand.

Nevertheless, in ten months neurosurgeon Nicholas Boulis from Emory University in Atlanta has delivered millions of spinal cord-derived fetal stem cells (supplied by Neuralstem Inc., an American biotechnology company) into the spinal cords of six ALS patients no longer able to walk because of their disease. Boulis uses a special “stabilized microinjection platform” for precision to target the injection to an area smaller than a grain of rice called the ventral horn. Three patients have received the cells on only one side of the spinal cord (so the other side can serve as a control), and another three have received bilateral injections.

Now Boulis and colleagues Eva Feldman from the University of Michigan and Jonathan Glass from Emory University (co-principle investigators for the trial) are recruiting ALS patients who can still walk, with the hopes that, when initiated early, cellular therapies will ultimately help preserve motor neuron function and delay disease progression.

“We began this trial with those who had severe disability and thus were at a lower risk for added weakness that may occur as a consequence of stem cell injection into the spinal cord,” the team wrote in a trial update posted on their web site. “We are now moving forward with patients with less disability.”

Their early concerns weren’t unwarranted. Like all experimental treatments, this one carries risks (including surgical ones) and the potential for serious side effects. There is evidence that injecting anything into the central nervous system can provoke inflammation, which in ALS is thought by some to accelerate disease progression. And certainly the risk of an immune response is heightened when the injectable contains cells that aren’t the patient’s own. However, the patients are reported to be doing well.

While the injected cells are capable of becoming motor neurons, it’s unlikely that’s how they might confer a benefit. To do so, they would have to project axons up to a metre long connecting to specific muscles. Rather, the cells might act as growth factor-spewing “biological minipumps” or as mops that “sop up excitatory amino acids like glutamate,” according to Colin Franz from the University of Calgary, who was involved with the trial at Emory.

But whatever the mechanism of action, finding a way to get stem cells into the spinal cord of vulnerable patients without causing more harm is an important and ambitious first step towards cellular therapies for people with ALS.

Comments

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