It may be the death of brain cells and not environmental or viral causes that bring on the onset of multiple sclerosis.
That’s what researchers at Northwestern University and the University of Chicago have concluded.
The scientists were able to trigger a disease that mimics multiple sclerosis (MS) in otherwise healthy mice. The disease developed after the rodents were injected with a protein that kills oligodendrocytes, the cells responsible for making the protective myelin coating for nerves cells.
The conclusion that the death of brain cells can trigger MS contradicts widely held theories that exposure to some external agent — whether environmental or viral — is the trigger. This study suggests that no matter how the process begins, the immune system is responding to the proteins released by dying brain cells.
According to a press release, an experiment within this same study showed that treating the mice with a nanoparticle targeted therapy could prevent MS from developing even after those brain cells die.The results of the study were published this week in the journal Nature Neuroscience.
Of Mice and Men
In order to test scientific theories safely, without causing harm to humans, scientists must first experiment with animal models for a disease. Traditionally, MS research has involved mice with a disease known as experimental autoimmune encephalomyelitis (EAE), which is similar to relapsing-remitting forms of MS.
For this study, however, scientists developed the first-ever progressive mouse model for MS. This new strain of mice may prove a pivotal tool in studying advanced forms of MS that have been frustrating researchers for so long.
“In most EAE models the disease is very acute,” Stephen D. Miller, PhD, professor of microbiology-immunology at Northwestern University Feinberg School of Medicine, said in an interview with Healthline.
Once the animals were injected with myelin protein along with an immune stimulant, the mice with EAE developed the disease one to two weeks later.
In this study, the genetically altered mice were at first disabled by the injections, and then appeared to recover spontaneously. It was only after six months that they developed the immune disease that looks like progressive MS.
“In that way, we think it was progressive and took a long time to onset in order to become recognizable,” Miller said.
This new mouse model of MS doesn’t appear to relapse, but does become worse, or progress, he added.
Flipping the Switch
Once the team had shown that MS could be triggered in mice by brain cell death, researchers treated the animals with a new therapy.
They used a delivery system comprised of microscopic particles known as nanoparticles. These particles are made from an FDA-approved copolymer that is easily metabolized. Researchers then loaded them with bits of protein found in myelin and injected them into the mice.
When the protein particles came in contact with the immune system, they were matched up with the myelin-specific receptors on the immune cells. This plugged the receptors and switched off the MS-like disease, leaving the rest of the immune system completely intact.
This method of action is in stark contrast to most other MS therapies, which act by dampening the entire immune system, leaving the patient vulnerable to infections.
One and Done
In their experiment with mice, the treatment triggered production of immune regulatory cells that “remember” that myelin is no longer an enemy. With just a single infusion, the therapy prevented the development of the MS-like disease in most of the mice involved in the study and halted the disease process in others.
But according to Miller, they still have a long way to go before this translates into a vaccine or even a viable therapy for MS patients.
“These particles are going to have to be injected in multiple species … to make sure there are no side effects,” he said. “But we have been doing this for five years now in mouse models and we haven't seen any adverse effects at all.”
On the Horizon
So when can people with MS expect to see this as a treatment option?
Unless researchers can raise the necessary funds through private donations, trials in these MS treatments are not likely to happen right away. According to Miller, none of the large pharmaceutical companies they’ve spoken with are interested in this as a treatment for MS since “the market is so saturated with MS drugs already.”
However, that doesn’t mean their research won’t continue.
“Our company, COUR, just signed a developmental deal with a large biopharma called Takeda Pharmaceuticals to develop this tolerance therapy for a different disease,” Miller said. “It's for celiac disease.
We've shown in animal models that we can both prevent and treat animal models of MS, type 1 diabetes, and others including celiac disease by taking nanoparticles and loading them with the specific autoantigen targets of the disease.”
The disease process in celiac disease is less complex than MS, according Miller, and researchers already know that gluten is the protein to target.
“So a lot of the drug companies might want to see a proof of concept in a much better understood autoimmune disease,” he said. “If we could show efficacy there, then I think the market is really going to open up where everybody's going to be interested in this.”