Targets and Treatments That May Hold Promise for Treating MS

The success of multiple sclerosis treatment went from zero to 60 in just a few decades. It was only 1993 when we saw the first disease-modifying therapy help stave off relapses and slow progression of the incurable autoimmune disease; now we have more than a dozen such medications, including one just approved that even provides some help for more aggressive MS.

Scientists believe the next few decades will likely bring more leaps forward for MS treatment. "Every year the field is learning how to better control the immune system. This means there's a good chance that more effective and specific therapies will be available to MS patients in the coming five or 10 years," says Christopher Jewell, an MS researcher and associate professor in the Fischell Department of Bioengineering at the University of Maryland.

[See: 10 Lessons From Empowered Patients.]

Retraining Cells

One of those treatments may fall within a category called immunotherapy, which harnesses the power of the body's immune system to fight disease. For example, some new cancer immunotherapies are helping to unmask normally "cloaked" cancer cells, which then enables immune cells to identify and kill these rogue cells in the body.

In MS, immunotherapy focuses on stopping the immune system from mistakenly attacking myelin (the protective coating on nerves), brain cells and optic nerves. We already have some important MS medications that help keep immune cells from attacking, such as natalizumab (Tysabri) and fingolimod (Gilenya). "But those types of treatments affect both healthy and diseased immune cells, which can compromise some normal function of the immune system," Jewell says.

Instead of blocking immune cells in a broad swath, Jewell and others are working on specific ways to "retrain" them. He and his team tested the idea recently by targeting T cells -- a type of immune cell -- in the lymph nodes, where the cells get their orders to attack myelin. "We designed polymer particles loaded with myelin and a regulatory signal called rapamycin that says, 'This is something that should be in the body; don't attack it,'" Jewell explains.

When scientists injected the loaded particles into the lymph nodes of paralyzed mice with MS, the results were exciting. "A single treatment reversed the paralysis. The mice could start walking and regained full use of their legs. These mice could also still mount immune responses against foreign molecules, so the treatment didn't appear to block other normal immune system functions," Jewell says.

That doesn't mean this approach will be the answer to MS; it's still in the experimental phase.

The team is now extending its work to other models of autoimmune disease (such as diabetes) and more stringent pre-clinical models to test if the approach might one day be effective for MS patients.

[See: 10 Seemingly Innocent Symptoms You Shouldn't Ignore.]

Regrowing Myelin

Another experimental area for MS treatment aims to jump-start oligodendrocytes -- the cells that produce myelin. Oligodendrocytes are damaged in the immune system's attack on myelin and nerves.

Previous research suggests that these damaged cells are missing miR-219, a type of microRNA. MicroRNAs are molecules that help regulate gene activity in cells.

Researchers at Cincinnati Children's Hospital Medical Center studied whether injecting synthetic miR-219 into the spinal columns and cerebrospinal fluid of mice with MS would reinvigorate damaged oligodendrocytes and flip on the genetic switch for myelin production. The results: "Treatment with this microRNA partially restored myelination and limb function," says lead researcher Dr. Richard Lu, scientific director of the medical center's Brain Tumor Center.

But again, this approach is still being investigated. Lu says the next step is to figure out how to ease delivery into brain tissue. "Large molecules such as microRNAs don't cross the blood-brain barrier on their own. But we and others are developing delivery strategies," Lu says.

Refocusing Targets

To cure MS one day, we'll have to understand the exact causes or triggers of the disease. At this point, we have only theories. But the work of a team at the University of Alberta in Canada offers a new target for research.

Cell biologist Thomas Simmen and his colleagues recently suggested, for the first time, that a potential MS trigger may be linked to proteins regulating the mitochondria -- the powerhouses in every cell in the body.

Together with clinician Fabrizio Giuliani, they discovered that levels of a protein called Rab32 were higher in MS brain tissue samples from humans and mice, compared to healthy brain tissue.

Rab32 normally tells a structure in each cell (called the endoplasmic reticulum) when to release calcium ions. This release helps control the energy-generating activity of mitochondria that migrate along the axons -- the nerve fibers that extend from a nerve cell (neuron) and communicate with other cells.

In the study, too much Rab32 was associated with brain cell death and axon shrinkage. "What we have not yet done is make the link with the immune system, but that research is underway," says Simmen, an associate professor in the university's department of cell biology. "Now we'd like to block Rab32 and see what happens."

[See: 9 Ways to Boost Your Immune System.]

The Takeaway

While new MS targets and potential treatments hold promise, they're still a long way off from actual disease management. It will take more years of study and experimentation to learn if they'll pan out.

But Simmen says there's every reason to have hope. "Our data on Rab32 have identified defects in mitochondrial energy production in MS. This discovery has opened up a key new avenue of research in addition to existing ones, which should accelerate efforts to find a cure. The more approaches we identify, the higher the chances one of them will work."

Heidi Godman is a freelance health reporter for U.S. News. Her work has appeared in dozens of online and print publications, including the Harvard Health Letter (where she serves as executive editor), the Chicago Tribune, Baltimore Sun, Orlando Sentinel and Cleveland Clinic Heart Advisor. Heidi also spent more than 20 years as a TV news anchor and health reporter. She's interviewed surgeons in operating rooms, scientists in laboratories and patients in all phases of treatment. Heidi has earned numerous awards for outstanding health reporting and was the first TV broadcaster in the nation to be named a journalism fellow of the American Academy of Neurology. Email Heidi at health@heidigodman.com.