In a recent experiment, mice with MS-like symptoms were able to walk and run again just two weeks after being injected with human neural stem cells. Even the researchers were unprepared for these incredible results. Though we're still far from a cure, it's a remarkable finding that hints at similar therapies for humans.
Multiple sclerosis is a motor neuron disease that affects more than 2.3 million people worldwide. The disease turns the body's immune system against itself, specifically myelin, an insulation layer surrounding nerve fibers in the brain. The resulting damage produced by immune T cells inhibits transmission of nerve impulses, resulting in symptoms such as limb weakness, numbness and tingling, fatigue, vision problems, slurred speech, memory difficulties, and depression.
Current treatment strategies, such as interferon beta, are aimed at curbing the autoimmune response, but researchers are now trying to find ways to stop or even reverse MS altogether. Such a strategy would bode well for patients with progressive stages of the disease for whom there are no treatments.
"An Excellent Model"
One such approach is the burgeoning field of cell transplantation therapy and the injection of induced pluripotent stem cells. In this case, specially engineered human neural stem cells were transplanted into the brains of mice in which MS-like symptoms (i.e. inflammatory-mediated demyelination) was kickstarted by inducing a viral infection of the central nervous system. It's not a perfect model of MS, but it's pretty damned close. As the researchers noted in their study:
Available evidence indicates that the cause of MS is multifactorial and includes genetic background and environmental influences. Although no clear causal relationship between MS and viral infection has been firmly established, viruses are capable of persisting within the [central nervous system] and have been implicated in initiating or exacerbating MS symptoms.
Concerned about the mouse model, I contacted senior author Thomas Lane from the University of Utah School of Medicine to get an explanation.
"No animal model is perfect," he told io9. "This is particularly true for MS in that many therapies that were shown to be successful in affecting disease progression either failed or made MS patients worse upon clinical trials. Nonetheless, we've employed what I feel is an excellent model in which neuroinflammation/demyelination is established and the animals display a clinical disease similar to what is seen in MS patients. We will test the therapeutic benefit of these cells in other pre-clinical models of MS."
And indeed, the mouse model closely approximated symptoms typically seen in MS; afflicted rodents had to be fed by hand because they couldn't stand long enough to eat and drink on their own.
Routine Experiment, Spectacular Results
Prior to the stem cell transplantation, Lane and colleague Lu Chen did not expect the mice to benefit from the treatments. In fact, they actually thought the mice would reject the cells, similar to the way an organ donor sometimes rejects a transplant. But less than two weeks later, the mice had regained their motor skills.
"My postdoctoral fellow Dr. Lu Chen came to me and said, 'The mice are walking.' I didn't believe her," said Lane.
"I was very surprised, although I went down and saw the animals myself and, indeed, motor skills were markedly improved," he told io9. "Subsequent experiments verified the initial observations."
Just as remarkably, the mice showed no signs of regression after six months. That said, the improvements represented a partial reversal of symptoms; immune attacks were blunted and the myelin repaired.
The researchers had this to say in their study, which now appears in Stem Cell Reports:
We found that [stem cell]-mediated recovery in our model was associated with a marked reduction in neuroinflammation, characterized by reduced infiltration of inflammatory T cells and macrophages within the spinal cords and emergence of regulatory T cells (Tregs).
They add that the stem cells are sending chemical signals that instruct the mouse's own cells to repair the damage caused by MS. They've pinpointed TGF-beta proteins, but there's likely more.
Not Your Ordinary Stem Cells
Dr. Lane is one of two senior authors of the paper, the second being Jeanne Loring of The Scripps Research Institute who developed the human stem cells. Scientists from the University of California (UC), Irvine, were also involved in the study.
The researchers engineered the stem cells in an unconventional way an important variable that influenced the outcome of the experiment.
Prior to transplantation, lead researcher Ronald Coleman grew the stem cells such that they were less crowded on the Petri dish than normal. This resulted in a batch of extremely potent stem cells. Importantly, their experiments have since been replicated at other labs using the new stem cell production protocol.
I asked Lane to explain the connection between the unique stem cell production protocol and the remarkable recovery shown in the mice.
"We are currently working through this as it is an extremely important question," he responded. "My opinion is that these cells were (1) extremely immunomodulatory and (2) they influenced the microenvironment to enhance demyelination potentially by "kickstarting" endogenous OPCs (oligodendrocyte progenitor cells) to become mature myelin-producing cells."
Interestingly, the original prediction that the stem cells would be rejected actually came true; the researchers were unable to find signs of the transplanted cells a week after the experiment, adding that "In MS, as in other neurodegenerative diseases, there is growing evidence that long-term survival of transplanted cells is not required for beneficial effects."
A Potential New Avenue For Treatments
Because the stem cells induced a chemical response, it's conceivable that the procedure could be translated to drug form.
"Rather than having to engraft stem cells into a patient, which can be challenging from a medical standpoint, we might be able to develop a drug that can be used to deliver the therapy much more easily," noted Lane in a statement accompanying the release of the study. "We want to try to move as quickly and carefully as possible...I would love to see something that could promote repair and ease the burden that patients with MS have."
But before they go to clinical trials, the researchers have to assess the durability and safety of the stem cell therapy in mice.
"It's too soon to say if human trials will follow," he told me, "although that is our long-term goal."
