Cerebral Palsy Center Combines Basic Research, Patient Care

Jason Carmel

By Alan Dove

The Weinberg Family Cerebral Palsy Center is unique in producing significant breakthroughs in both basic science and patient treatment and is the only CP center in the nation to incorporate basic research into its program.

The center provides comprehensive lifetime care for people with cerebral palsy by coordinating clinical services across medical specialties, offering both pediatric and adult care, and providing support programs and mental health services. Including the entire research pipeline in one place, from laboratory bench to clinical trial to treatment, keeps the team focused, says Jason Carmel, MD, PhD, the center’s executive director. “Having it all under one roof gets those conversations going about what the best experience is that we need to do, in order to show that it’s going to be helpful, that it has a path toward people.”

The center’s projects have illustrated the effectiveness of that approach. In one project, Dr. Carmel and his colleagues began with a human study on children with hemiplegic CP, in which damage to one side of the brain leads to a loss of function on one side of the body. “We found that a kid’s ability to use their hand was much more tied to the integrity of their sensory system, compared to the motor system, which is against conventional wisdom,” says Dr. Carmel, the Weinberg Family Associate Professor of Neurology. 

Taking those results into the lab, the team analyzed the phenomenon in rats, confirming the human findings and revealing how hemiplegic damage affects the nervous system. Motor neurons appear to adapt better to damage, rerouting signals so the undamaged side of the brain can control both sides of the body. Sensory neurons, however, don’t adapt as well. Electrically stimulating both motor and sensory nerves partially restored their lost dexterity.

It’s exactly the sort of breakthrough envisioned for the center, which opened in 2013. “The inclusion of a research program enables us to understand the safety and efficacy of an approach before initiating trials in people,” says Dr. Carmel.

Scientists at the center are also looking at the possibility of combining spinal cord stimulation with brain stimulation. All forms of skilled movement, from writing a name to hitting a tennis ball, require two sets of signals between the brain and muscles: motor signals from the brain for the muscles to move and a return set of sensory signals to keep the brain aware of the body’s position and the environment. “We think that a critical site for those signals to interact is at the level of the spinal cord,” says Dr. Carmel.

Recent research at the center has shown that stimulating both the brains and spinal cords of animals with nervous system injuries can decrease spasticity and improve limb function. The team is testing this approach in the operating room in people undergoing surgery. They are also trialing the approach using non-invasive stimulation of brain and spinal cord. 

In another project, Dr. Carmel and his colleagues have been exploring the causes of CP. Traditionally, doctors have been taught that people acquire CP during development, most often when premature birth, infection, or other environmental factors damage the nervous system or derail its development. “What we’ve learned more recently is that genetics also plays a large role,” says Dr. Carmel, adding that the center is part of a major research consortium trying to understand how genetic risk factors are involved in the condition.

The team is also trying to refine diagnosis. Like many other neurological diseases, CP occurs across a spectrum. One patient could walk with a slight limp while another is confined to a wheelchair. “We need to figure out the way the nervous system is wired and then really treat that person with more of a personalized medicine approach,” says Dr. Carmel. The center is part of the Cerebral Palsy Research Network, which uses data from large cohorts of patients to pursue precision medicine approaches. It’s not just an academic interest. With more therapies becoming available, he adds, it’s important to figure out which treatments are most likely to work for each patient.

Dr. Carmel is cautiously optimistic about the future of CP care and research. “Medicine is notoriously always five years away from a cure,” he quips, but the CP field is moving rapidly toward tailored treatments and more of them. Basic and clinical research in other fields is also propelling progress in CP. “Because of the success of neuromodulation in other conditions, such as Parkinson’s disease and spinal cord injury, I think that there’s going to be some electrical stimulation-based approaches in the clinic soon.” 

A $6.5 million donation given to the center last year will enable the center to expand both its research and clinical care programs. The donation came from Deborah and Peter Weinberg, the center’s original benefactors. While grants from outside funding agencies, including the NIH, cover individual basic research projects at the center, the new donation will support additional clinical laboratory space, a full-time clinical researcher, and expansion of the multidisciplinary clinical team.