The Search for MS Therapies Is On

Multiple sclerosis is becoming more prevalent in children, especially in the Pacific Northwest. Our researchers are developing innovative therapies to end its destructive toll.

ONeill Ferri

Sara O’Neill, 17, visits with Dr. Ray Ferri, who started the region’s first pediatric MS clinic. Though a medication lengthens the time between Sara’s flare ups and limits their severity, she wonders how MS will affect her in the future and looks forward to a day when MS is a disease of the past.

When Sara O’Neill was 14, her hands and feet started tingling and going numb, and she felt electric-shock sensations down her spine. Her pediatrician thought she had a virus until a year and a half later, when a dark smudge appeared in her vision and left her 80% blind in one eye. After a trip to Seattle Children’s emergency room and a battery of tests, Sara received a staggering diagnosis: multiple sclerosis (MS).

MS occurs when the body’s immune cells attack the myelin sheath that surrounds nerves in the brain and spinal cord, disrupting the nerves’ ability to carry electrical signals that tell the body what to do. Most people think of MS as an adult disease, but it’s increasingly being seen as a disease that starts in childhood – especially in the Pacific Northwest, where MS is more prevalent than anywhere else in the United States. Researchers don’t know why the disease is more common here or why it’s becoming more common among children.

Dr. Mohamed Oukka is at the forefront of identifying the mechanisms behind MS and is working with his colleagues on new therapies that could stop it from causing mental and physical disabilities in children like Sara.

“Today’s MS drugs aren’t always effective and can leave patients open to serious, even fatal infections,” Oukka says. “We’re developing treatments that could be more effective, without those side effects.”

Pediatric MS care needed

Multiple Sclerosis Connection Fall 2013

In MS, a person’s immune system overreacts and attacks the myelin sheath – a protective cover that insulates nerve cells in the brain and spinal cord. The top illustration shows how MS damages that sheath and disrupts the nerves’ ability to send signals to the rest of the body.

About 400,000 Americans have MS, including about 10,000 children. Children usually suffer from relapsing-remitting MS, where immune cells periodically attack the nervous system. Each attack degrades the nerves a little more. In the worst cases, the disease progresses until patients suffer physical weakness, cognitive problems and chronic pain.

About a year after Sara was diagnosed, she had a severe attack that left her hospitalized for three days. Since then, she has struggled with depression and fatigue, and she believes the disease affects her thinking.

Sara takes a drug called Tecfidera to prevent relapses. Like many MS treatments, the drug works by reducing the number of white blood cells to dampen the body’s immune activity.

“These therapies have turned MS from a potentially debilitating disease into something that can be managed long-term,” says Dr. Ray Ferri, who started a pediatric MS clinic in 2009 after noting the growing need for MS care. The clinic remains just one of two on the West Coast. 

However, the most popular MS drugs block all T cells from getting into the brain, a problem that can lead to fatal infections.

Pursuing innovative treatments

Oukka was part of a team at Harvard University that identified the specific type of T cells, called Th17 cells, that attack the myelin sheath. Now his team at Children’s is investigating whether infusions of a hormone called IL27, which naturally suppresses Th17 cells, can make them less active while leaving other T cells free to protect the brain from viruses.

Children’s researchers are genetically reprogramming immune cells to find and destroy the cells that attack patients’ nerves.

Oukka is also working with Drs. Andy Scharenberg and David Rawlings, who are genetically reprogramming immune cells to find and destroy Th17 cells. The researchers are testing this approach in mice. If it works, they aim to start human clinical trials as soon as possible.

“Ideally, the patients wouldn’t have to take medication on a regular basis – the modified cells would do all the work,” Oukka says.

Searching for genetic causes

Oukka Torgerson

Drs. Mohamed Oukka (left) and Troy Torgerson hypothesize that mutations in certain genes trigger the onset of MS in early adolescence. They are currently sequencing the genomes of teens with and without MS to help pinpoint the genetic defects that cause MS in early life and shed light on whether those defects match those carried by adults with MS.

Oukka and Ferri are also teaming up with Dr. Troy Torgerson and others to sequence the DNA of children with MS. Their goal is to identify which genes work together to cause the disease, opening the door to other therapies that could actually cure it.

“We want to correct the genes so the immune system behaves normally,” Oukka says.

This gives new hope to patients like Sara, now 17. Her blindness is almost gone, she’s starting to play sports again and she’s passionate about learning to speak Japanese – she spent a month this past summer living with a family in Kobe, Japan.

“Sometimes I actually forget I have MS,” Sara says. “I know it doesn’t have to be severe and that people are working on cures – and that’s pretty cool.”

Published in Connection magazine, September 2013