NeuroDevNet cerebral palsy research spans prevention, rescue and regeneration

October 7, 2015

One project is investigating how eating broccoli sprouts can prevent cerebral palsy (CP). Another incorporates fire-spitting geckos into a rehabilitation exergame system. A third has amassed a National CP Registry with more than 1,500 patients.

As we celebrate World Cerebral Palsy Day 2105 around the globe, we’d like you to meet members of NeuroDevNet’s Cerebral Palsy research team of top Canadian investigators and researcher-clinicians who use their diverse expertise to improve the lives of children and families affected by the most common childhood motor disability.

“This is a research group that covers pre-clinical animal work all the way to knowledge translation,” says Dr. Darcy Fehlings, lead principal investigator of the CP research program. “It’s really exciting to have a national team like this, and it’s really important to have this broad depth and breadth of focus for a better understanding of cerebral palsy.”

Underlying causes now include genetic mutation
 CP is a neurodevelopmental disorder that occurs when the developing brain is damaged during pregnancy, delivery, or in the first several years of a child’s life. Symptoms range from mild to severe, and include impairment with muscle tone, fine motor functions, reflexes, and balance.

Under the umbrella of CP, the severity and type of disability can vary considerably. People with CP face a wide range of health challenges that may require numerous surgeries and extensive rehabilitation.

Our CP researchers Drs. Michael Shevell and Maryam Oskoui (right) and their collaboration with Dr. Stephen Scherer, co-lead of NeuroDevNet’s autism research group and a pioneer in autism genetics, made front page news in early August 2015. Duplications, deletions and/or reorganization of segments of DNA in families with children with CP suggested for the first time that our genes impart resilience - or the reverse - a susceptibility to brain injuries that cause the symptoms of CP.

Now entering their sixth year of collaboration, the CP research team is concentrating on advancing their numerous groundbreaking projects.“NeuroDevNet has been instrumental as a catalyst in bringing all the CP researchers in Canada together,” said Dr. Jerome Yager, co-principle investigator.
“We have a phenomenally strong group of investigators across the country, and we plan to really make an impact on the understanding - and hopefully treating - kids with CP.”
Creating multiple models around known causes of CP as a foundation
No single cause for CP has been identified, but the CP research group has successfully developed three models of the disorder:
  • placental insufficiency, a complication of pregnancy when the placenta is unable to deliver enough nutrients and oxygen to the fetus to support typical development;
  • fetal inflammatory response, a condition where systemic inflammation is seen in fetuses with preterm labor, and also fetal viral infections such as cytomegalovirus, and
  • neonatal stroke – a stroke that occurs before or soon after birth that is thought to cause 70 to 80 per cent of identified cases of CP.
Over the next five years, the group will focus their research on prevention, rescue, and regeneration strategies arising from these underlying causes.
Dr. Yager continues his work on the neuro-protective benefits of the natural health product broccoli sprouts. In previous work, his lab confirmed that consuming broccoli sprouts during a rodent’s pregnancy can not only prevent brain injury - but these benefits are long

Dr. Yager’s work spans prevention to include rescue – intervention when inflammation is known to be present. By 2020, his dream is to have a user-friendly broccoli sprout dietary supplement for pregnant woman.“It’s not as easy as it might sound – it’s not just like crushing up a bunch of sprouts and putting it in food form,” he says, chuckling. “We have to figure out a way to make it available and effective in a form that does the same as the natural food does. But it’s certainly doable.”

CPDP’s regeneration team is being led by neurosurgeon Dr. Michael Fehlings (University of Toronto). His lab is focusing on research to validate neural stem cell transplantations in mice to repair brain damage. Initial findings have been significant, and the team hopes to begin human clinical trials approximately five years from now.
Prakasham Rumajogee, (right) a post-doctoral fellow working in the Fehlings lab, speaks of the promise of the work, and the necessity of careful monitoring to establish that implantation of stem cells – the right type, in the right amount, in the right animal models, in creating the groundwork for eventual human trials. Enormous urgency presses against this approach, but Dr. Rumajogee emphasizes unchecked cell growth and replication can lead to outcomes no one desires, including brain tumors.
Additional research Dr. Rumajogee is carrying out in the Fehlings Lab complements work being supervised by Dr. Derek van der Kooy exploring the mechanisms that underpin the effectiveness of constraint induced movement therapy.  Constraint therapy is an increasingly popular treatment to improve mobility in limbs affected by CP whereby the unaffected side is restrained, forcing the affected arm or leg to do more work.
National CP Registry
The Jewel in the NeuroDevNet Crown, the trans-Canadian National CP Registry is the first tool of its kind in North America, says CP research group Lead Dr. Darcy Fehlings. NeuroDevNet funds its work in Quebec, Alberta, and the Greater Toronto Area, enabling Researcher within NeuroDevNet as well as investigators outside the Network to explore whether there are regional differences in the frequency and severity of cerebral palsy within Canada, and internationally.
These are some of the questions that the National CP Registry, being spearheaded by Drs. Shevell and Oskoui, which now holds more than 1,500 samples.
“We really want to start to utilize it as a tool to discover things about CP,” says Dr. Fehlings. “Now that we’ve had a few years where we’ve gotten lots of children in, we want to do a dive into regional differences in the spectrum of CP and the prevalence across Canada.”

Liberi Exercycle improves fitness and increases social interaction
The brainchild of Dr. Darcy Fehlings (below, on the right) and researchers from the GRAND NCE, the Liberi exercycle, and one of the games it powers is the source of the fire-spitting geckos in the lead into this story. The customized exercycle whose pedals, powered by youth with CP, run customized multi-player videogames played both remotely and in person via headsets has shown cardiovascular benefits, as well as what one study participant described as life-changing impacts on his social life. The dual impact is very encouraging to both researchers and teens in the study. Physical activity in this age group often dwindles, and social isolation increases.

Epigenetics of CP in Preterm-Born Infants
Premature babies that have had a postnatal infection are twice as likely to develop cerebral palsy – and Dr. Steven Miller wants to understand why.
Initial data suggests that postnatal infections result in gene (epigenetic) expression that could influence early brain development. His project is exploring whether preterm infants exposed to infection have adverse developmental outcomes – and whether epigenetic changes are the root cause of this.
Dr. Miller (left) will also continue his research on the potential of post-natal Magnesium Sulfate (MgSO4) to decrease the risk of brain injury in preterm infants.
“The main issue isn’t so much tissue destruction, but that the brain just isn’t developing normally,” says Dr. Miller. “We want to find out how to unstick this abnormal process of brain development to allow things to proceed normally.”
Ensuring research insights reach those who can put them into action
Drs. Annette Majnemer and Keiko Shikako-Thomas are leading the CP Research group’s knowledge translation (KT) efforts. Going from ideas to action is different from what is traditionally done by researchers, says Dr. Majnemer.
A key example is the development of the App JOOAY, a database of different sport, arts, camps and other activities adapted to children and youth with disabilities.
“It came from a research project as a means to help promote participation,” says Dr. Majnemer. “We found a number of different barriers to children participating in different physical activities. And it’s not that they don’t want to do these activities - they really do. So we thought an app would be a really simple solution to this problem.”
Launched in spring 2015, the App is slated to be available for android, IOS, and in website form, with initial data from Quebec, Ontario, B.C., Saskatchewan, and Alberta. The database within the App continues to expand with funding from NeuroDevNet, the Rick Hansen Foundation and other organizations.
Another KT contribution is the CP research group’s annual CP in Motion conference, a very successful mechanism that has enabled connections with the community if families with CP, service organizations across Canada, and policymakers. Their combined forces help promote increased research funding and resources for youth with neurodevelopmental disabilities.


Top: Dr. Michael Shevell and Dr. Maryam Oskoui collaborated with Dr. Stephen Scherer in a groundbreaking study of the role of genetics in cerebral palsy supported by NeuroDevNet. / Photo courtesy of McGill University Health Centre (MUHC) Public Affairs 

Prakasham Rumajogee: Fehlings Lab, University of Toronto

Exergame image: Holland Bloorview Kids Rehabilitation Hospital Public Affairs