Priorities in Cerebral Palsy Research

June, 2012

Given limited funding resources, differences of opinion often arise over whether research priorities should focus on prevention and cure or on applications that enhance function and quality of life for those with cerebral palsy.

An excellent example of a current basic science approach to prevention and cure (or at least to reduction of the severity of motor impairment in cerebral palsy) is a research project funded by the Cerebral Palsy International Research Foundation (CPIRF) and conducted by Dr. Vittorio Gallo, Director of the Neuroscience Research Program at Children’s National Medical Center in Washington, DC.  Under Dr. Gallo’s direction, postdoctoral fellow Dr. Matthew Raymond is conducting a study entitled “The Role of Astrocytes in Cerebral Palsy.”  Here is a summary of their ongoing work.

 
     Besides actual neurons (nerve cells) in the brain, there are two other essential cells that sometimes do not get much attention. One is called an oligodendrocyte (oh-lee-go-den-dro-site, IPA oʊ.li.goʊ.ˈdɛn.dɹoʊ.saɪt) whose function is to create the outer, insulating layer (myelin) of the long projecting arms (axons) of neurons. Because myelin is mostly whitish fat, it constitutes the brain’s so-called “white matter.” The main purpose of myelin is to speed up nerve impulses that travel along its fibers, thereby increasing the efficiency of motor, cognitive, and language commands. When white matter fails to develop or is injured during a crucial developmental time period during the third trimester of pregnancy, these functions, especially motor, can be impaired, resulting in spastic-type cerebral palsy.

     Star-shaped astrocytes (a-stro-sites, IPA ˈæs.tʃɹoʊ.saɪts)  are the most abundant cells in the brain. They also play an important supporting role to the neurons. Their many tasks include provision of nutrients to neurons, maintaining chemical balance in surrounding fluid, and repair after injury.

     Lack of oxygen to the brain (hypoxia) is a major factor responsible for white matter damage that can lead to cerebral palsy. The immature lungs of very premature infants make them particularly vulnerable to the effects of hypoxia. Oligodendrocytes, the producers of white matter, are known to be very susceptible to hypoxic injury. However, much less is known about the effects of hypoxia on astrocytes.

     Drs. Gallo and Raymond are studying how astrocytes can be encouraged to remove excessive amounts of a normally present stimulative chemical in the brain called glutamate. Too much glutamate can kill oligodendrocytes. In this way, white-matter damage associated with cerebral palsy might be preventable. Furthermore, astrocytes have stem-cell potential, meaning they could actually turn into oligodendrocytes that would produce and replace essential white matter.

 
Studies such as the one described above have important implications for the development of therapies that prevent or cure cerebral palsy. Certain chemical pathways in the brain and specific cell populations are attractive targets for early medical intervention. Modification of these targets can potentially prevent or reverse white matter damage in the premature infant susceptible to cerebral palsy.

In contrast, Dr. Peter Rosenbaum, Professor of Pediatrics and Chair of the CPIRF Scientific Advisory Council states, “We have very few opportunities, at the present time, to prevent or cure conditions [like cerebral palsy].  In an article entitled, “The ‘F-words’ in Childhood Disability: I swear this is how we should think!” (Child: Care, Health and Development, preprint publication online 1 Nov, 2011), he describes the expansion of the World Health Organization’s 2001 International Classification of Functioning, Health and Disabilities (ICF). The new classification includes aspects of disabling conditions that go beyond the limits of traditional medical interventions to such areas as enhanced quality of life and full participation in family and community activities.

Dr. Rosenbaum does not dismiss the importance of basic science research to promote or cure cerebral palsy or other disabling conditions nor clinical research to develop new treatments that reduce unwanted symptoms of cerebral palsy, such as drug therapies for spasticity or robotics for enhanced mobility.  Rather, he encourages readers to expand (not reject) traditional biomedical concepts by considering more dynamic, empowering notions of clinical service, research and advocacy that incorporate ICF concepts of full participation in family life, recreational activities, and meaningful education and employment. To this end, Professor Rosenbaum’s proposes six guiding “F” words: function, family, fitness, fun, friends and future.

Prevention and cure, on the one hand, and optimization of function, participation, and quality of life, on the other hand, should not be viewed as separate or competing research goals but rather as a continuum. Surely, no person with a disability would argue against research aimed at prevention of cerebral palsy; yet, for thousands of individuals living with cerebral palsy (and their families) achieving the “F” words to the fullest extent deserves equal emphasis.

Increasingly, proposals for research at the most basic laboratory level must clearly identify how the results of their discoveries will yield positive results for the lives of people, if not in complete prevention, then in improving potential for achieving the highest quality of life.

The Cerebral Palsy International Research Foundation, along with its partner UCP, is committed to fostering high quality research along the continuum from basic to applied. Your interest in and questions about our efforts are always welcome.