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 tinglingand going numb, and she felt electric-shock sensations downher spine. Her pediatrician thought she had a virus until ayear and a half later, when a dark smudge appeared in hervision and left her 80% blind in one eye. After a trip toSeattle 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 themyelin sheath that surrounds nerves in the brain and spinalcord, disrupting the nerves’ ability to carry electrical signalsthat tell the body what to do. Most people think of MS as anadult disease, but it’s increasingly being seen as a diseasethat starts in childhood – especially in the Pacific Northwest, where MS is more prevalent than anywhere else in theUnited States. Researchers don’t know why the disease ismore common here or why it’s becoming more commonamong children.

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

“Today’s MS drugs aren’t always effective and can leavepatients 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 andattacks the myelin sheath – a protective cover that insulates nerve cellsin the brain and spinal cord. The top illustration shows how MS damagesthat sheath and disrupts the nerves’ ability to send signals to the rest ofthe body.

About 400,000 Americans have MS, including about 10,000children. 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 worstcases, the disease progresses until patients suffer physicalweakness, cognitive problems and chronic pain.

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

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

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

However, the most popular MS drugs block all T cellsfrom getting into the brain, a problem that can lead tofatal infections.

Pursuing innovative treatments

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

Children’s researchers aregenetically reprogrammingimmune cells to find anddestroy the cells that attackpatients’ nerves.

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

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

Searching for genetic causes

Oukka Torgerson

Drs. Mohamed Oukka (left) and Troy Torgerson hypothesize that mutationsin certain genes trigger the onset of MS in early adolescence. They arecurrently sequencing the genomes of teens with and without MS to helppinpoint the genetic defects that cause MS in early life and shed light onwhether 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. Theirgoal is to identify which genes work together to cause thedisease, opening the door to other therapies that couldactually cure it.

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

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

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

Published in Connection magazine, September 2013