Saving Superman: Alison Kraemer ’12 Takes on Paralysis

CHARISSA ILUORE

Neuron

Christopher Reeve was a hero. For nearly a decade, the talented actor played the role of Superman in a series of four huge box-office films. He put on thirty pounds of muscle for the role and, with his towering six-foot-four figure, he definitely looked the part. When production on the last movie in the franchise wrapped, Reeve began to look for new diversions to occupy his time.

After learning the skill on one of his other films, he took up horseback riding almost full time, competing in events all over the nation. As with everything else, Reeve was incredibly good at riding; at the finals of a championship in Virginia, Reeve had already captured fourth place out of twenty-seven in the dressage prior to riding the cross-country course. He carefully appraised the jumps fearing that some were especially difficult, but decided to proceed nonetheless.

Reeve’s horse stopped short at one of the first obstacles and sent its rider flying headfirst, his skull meeting the ground with astonishing force. The six-foot-four frame that had served him so well in his role as Superman collapsed into the earth like an accordion, crushing his first and second vertebrae, and leaving him paralyzed from the neck down. Though seriously injured by the tragedy, Reeve committed to helping others. Until his death in 2004, Reeve dedicated himself to leading a charitable foundation which he established dedicated to advancing stem cell research to cure paralysis.

Christopher Reeve was a hero, not because he suited up in a flashy costume and played a character, but because he bravely surmounted all obstacles, using his accident to inspire good. Among those inspired by his courage was Harvard alumna Alison Kraemer ’12, a Human Developmental and Regenerative Biology concentrator who sought out a research position in Dr. Paola Arlotta’s lab, which studies the embryonic development of corticospinal motor neurons—neurons whose damage results in paralysis.

During her time in the lab, Kraemer worked on a project that aimed to create a foundation for possible future work that could convert non-embryonic stem cells into neurons found in the spinal cord. “I was trying to differentiate human induced pluripotent stem cells into corticospinal motor neurons, neurons that go from your [cerebral] cortex to your spine,” Kraemer explains. Her work focused on those neurons that permit voluntary motor control and are involved in diseases like ALS (Lou Gehrig’s disease), Hereditary Spastic Paraplegia (HSP), and spinal cord injury.

It is important that we do not lose sight of the societal implications while we are doing science.

In the long run, researchers are hoping to create a cure for spinal damage, but more research remains to be done about these conditions’ origins and processes. To study these diseases more closely, it would be helpful to be able to replicate them in the lab. For instance, having the capability to artificially induce ALS in human non-embryonic stem cell lines and follow the life cycle of those affected cells would give researchers tremendous insights about how the disease really works. “If [we] could model the disease in a dish in the lab… [we] could induce a mutation in the gene for ALS. When you differentiate those cells, you would end up with corticospinal motor neurons that are affected with ALS,” Kraemer says. As a result, scientists could watch the disease manifest in real time, analyze its behavior, and explore the means by which it is able to destroy neurons.

However, despite three years of such intensive research that eventually culminated in her senior thesis, the project was not able to successfully differentiate preneural cells derived from non-embryonic stem cells into mature corticospinal motor neurons. Inquiry in the lab still continues, though, and there is hope for an eventual breakthrough.

A larger roadblock to an eventual cure is that even if Dr. Arlotta or researchers in another lab do eventually succeed in converting non-embryonic stem cells into specific neurons, there is no clear procedure for using those neurons to cure spinal degenerative diseases. “You could try to target neurons in the cortex where they would grow down into the spinal cord, but that would be risky since you would be injecting cells directly into the brain,” Kraemer says. A similar problem occurs with injecting neurons directly into the spine. Though corticospinal motor neurons could in theory be used as a “neural bridge” to re-connect damaged parts of the spinal cord, they are not normally found there as whole entities. Only the axons of the neurons, the extensions of the cells which send messages to muscles and other neurons, are found in the spinal cord. Thus, injecting whole neurons into the spine could be problematic.
Beyond practical difficulties, there are the ethical problems associated with stem cell treatment.

To those who are still skeptical about this controversial form of therapy, Kraemer calls on scientists to keep questioning. “There are all of these societal questions about how we far we are willing to manipulate our bodies, how far we are willing to manipulate the cells that grow into full humans,” she says. “It is important that we do not lose sight of these societal implications while we are doing science.”

What is certain is that Kraemer, now a first year medical student at Johns Hopkins, will remain dedicated to the cause of improving existing health care and finding new treatments so that patients like Christopher Reeve can have hope of a better tomorrow.

Charissa Iluore is a Brevia staff writer. She can be reached at ciluore@college.harvard.edu.

CORRECTION 3/15/14: An earlier version of this article misrepresented the progress made on the project. It did not succeed in differentiating corticospinal motor neurons affected by ALS from non-embryonic stem cells.