Turning Research Into Results 2017 Gratitude Report
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table of contents
4 Mind Over Movement
A new study examines the benefits of tai chi for kids with ADHD.
8 Building Muscle That Lasts
Kennedy Krieger is at the forefront of developing drugs for muscular dystrophy to help kids like Dylan.
12 Infographic: Research at Kennedy Krieger Our research makes a world of difference to more than 24,000 kids each year.
14 Measure Improvement, Anticipate Success Tools developed at Kennedy Krieger allow for more accurate prognoses after brain injury.
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Unmasking Rare Diseases By studying diseases at the genetic level, we’re able to help kids like Andrea excel every day.
19 Why Give?
Here are just a few reasons why your gift matters.
KennedyKrieger.org/17Gratitude • 443-923-9200 To learn more, get involved and stay connected, visit KennedyKrieger.org/Connect.
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Dear Friend, In this year’s Gratitude Report, we look at how four of our faculty members and their colleagues are applying their research to achieve positive, often life-changing results in the treatment of our patients. Here, you’ll read about a team led by Dr. Stewart Mostofsky that is studying the effects of mindful movement on children with ADHD while helping kids like Atticus have fun. You’ll learn about how Dr. Ali Fatemi and his colleagues are tailoring novel treatments for patients with rare leukodystrophies. You’ll also learn about the Kennedy Krieger Scales—a measurement developed here by Dr. Beth Slomine and other brain rehabilitation experts and now used around the world to assess children like Garrett, who’s recovering from a traumatic brain injury. And, you’ll read about what Dr. Kathryn Wagner and her colleagues are doing in both lab and clinic to give children with a life-threatening form of muscular dystrophy a chance at life. I hope these stories about brilliant researchers and amazing kids will inspire you as they inspire me. Their determination to overcome brain injuries and rare diseases can teach us much about the life-affirming powers of visionary thinking, hard work and a positive attitude. Developmental disorders of the brain affect one in six children—about 12 million kids—in the U.S. alone. At Kennedy Krieger Institute, we serve children from around the world through the work we do in our clinics, schools and labs, where we’re uncovering causes of—and treatments for—brain, spinal cord and musculoskeletal disorders. Of course, none of this would be possible without our donors. Your support helps our faculty members translate their research from lab to clinic, helping children benefit from the advancements and discoveries that happen at Kennedy Krieger. And, your support helps fund the next discovery that’s right around the corner. We are extremely grateful for your ongoing support of our work. Sincerely,
Above and on the cover: Patrick, who has osteogenesis imperfecta, is one of Dr. Mahim Jain’s patients. Dr. Mahim Jain is a member of Kennedy Krieger Institute’s Osteogenesis Imperfecta Clinic, where he treats patients with osteogenesis imperfecta (OI), also known as “brittle bone disease.” His research focuses on low bone density disorders and on finding new ways to treat patients with these disorders. Currently, Dr. Jain is studying the growth parameters of children with OI and plans to develop clinical guidelines for their expected growth. He’s identified, or contributed to the identification of, genetic variants that lead to various disorders including OI, other skeletal disorders and attention deficit hyperactivity disorder. Read more about his work at KennedyKrieger.org/MahimJain.
“At Kennedy Krieger, I can pursue both my love of scientific research and my passion for caring for kids like Patrick.” —Dr. Mahim Jain, MD, PhD
Amy Bastian, PhD, PT Chief Science Officer, Kennedy Krieger Institute
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leven-year-old Atticus is waiting for his tai chi class to begin. He selects a large blue exercise ball—one with a handle—sits on it and deftly bounces around the room, his slight frame belying his boundless energy.
“It’s hard to get me tired,” Atticus says to his instructor, Dr. Dav J. Clark. Atticus has attention deficit hyperactivity disorder, known as ADHD, and is one of about 30 children participating in a three-year study at Kennedy Krieger Institute that looks at how an ancient movementand mindfulness-based practice can help children control ADHD symptoms like hyperactivity, impulsivity and inattention. ADHD is the most common behavioral diagnosis among children in the U.S., and it affects as many as 10 percent of children around the world. Children with ADHD often suffer from poor academic achievement due to difficulties with motor and behavioral control. Untreated, they’re at a higher risk than their peers for developing a mental illness, substance abuse or criminal behavior in adulthood. The personal and societal costs of ADHD are high. Each year in the U.S., ADHD-related spending— including healthcare, education, and income and productivity losses—totals $143 billion to $266 billion, according to a report published in the Journal of the American Academy of Child and Adolescent Psychiatry.
Each year in the U.S., ADHDrelated spending—including healthcare, education, and income and productivity losses—totals $143 billion to $266 billion. Dr. Dav J. Clark (center row, left) leads a tai chi class with research assistant Heather Thompson (center row, right). Students participating include (from left to right): Wyatt, Kelvan, Atticus and Sara.
As part of the tai chi study, which is being led by Dr. Stewart Mostofsky, director of Kennedy Krieger’s Center for Neurodevelopmental and Imaging Research, small groups of children with ADHD attend tai chi classes twice a week for eight weeks with Dr. Clark, a Kennedy Krieger research scientist and neuroscientist as well as a tai chi practitioner and teacher of mindful movement. Dr. Mostofsky sees ADHD as a brain-based behavioral disorder. With the study, he’s looking to find out if engaging the sensorimotor system through movement- and mindfulness-based practice improves not only motor control but also behavioral control. Get the brain used to acting in a controlled way during tai chi, he theorizes, and the brain may be more likely to be able to control behavior outside the class, too. Dr. Mostofsky received a grant from the National Institute of Mental Health to fund the study. He chose tai chi over other forms of movement- and mindfulness-based practice because it seemed like the best choice for children. Yoga, he figured, might be too strenuous for some of the children, and meditation too motionless. A few studies have shown that tai chi can help adults with ADHD achieve some level of control over their actions and behavior, but this is the first significant study to look at tai chi’s effect on children with ADHD. “And because there is tremendous brain plasticity in childhood, which decreases in adolescence,” Dr. Clark adds, “practicing tai chi now could make a huge difference in these kids’ lives.” Many children with ADHD take medication to control their symptoms, but medication can come with side effects like tiredness, insomnia, stomach aches and changes in appetite. Movement- and mindfulnessbased practices like tai chi may hold the key for those who want to reduce the amount of ADHD medication they’re taking, Dr. Mostofsky says. >>
Dr. Dav J. Clark (left) and research assistant Heather Thompson (right) talk with Dr. Stewart Mostofsky, who is leading a study that looks at the effects of tai chi on kids with ADHD.
“Get the brain used to acting in a controlled way during tai chi, and the brain may be more likely to be able to control behavior outside the class, too.” —Dr. Stewart Mostofsky, MD, director of the Center for Neurodevelopmental and Imaging Research at Kennedy Krieger Institute
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Promising Results Before the first class, Atticus and his fellow tai chi pupils each filled out a questionnaire asking them what they hoped to get out of the eight-week session. Most indicated they were optimistic that tai chi would help them control their behaviors and body movements. “Some kids say they hope the tai chi will help them concentrate on their homework or just allow them to calm down a bit,” says research assistant Heather Thompson, who’s managing the study. Because ADHD affects motor skills as well as behavior, each child also took a motor assessment before the first class, performing balancing, hopping and object-tossing exercises to demonstrate motor coordination and gross motor skills. Short exercises on a computer helped researchers assess the children’s attention and behavioral control.
Wyatt, Dr. Dav J. Clark, Sara, research assistant Heather Thompson and Atticus practice tai chi.
“Some kids say they hope the tai chi will help them concentrate on their homework or just allow them to calm down a bit.” —Research assistant Heather Thompson
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For Atticus, who’s currently taking medication, “the goal is to get him to a point where he can say, ‘I think I can manage ADHD on my own,’ without medication,” says his mom, Tina, who enrolled her son in the study so they could learn more about alternative methods for treatment. “Overall, the experience has been really great,” she says. Encouraged by improvements she noticed in her son over the course of the study, she enrolled him in therapy sessions and worked with his therapist to include tai chi in his treatment plan.
At the end of the program, each child will complete another assessment of motor and behavioral control as well as questionnaires assessing ADHD behavior. In the post–tai chi motor assessments, Dr. Mostofsky, Dr. Clark and Thompson are looking for improvements in behavioral response control, attention, motor control and coordination. The kids’ parents also take post–tai chi questionnaires asking them about their children’s level of attentiveness, hyperactiveness, impulsivity and other behavioral features, such as mood. So far, questionnaire responses have indicated that the tai chi classes help the children to be more cognizant of how they’re feeling and what they’re doing, and that they help improve the kids’ attentiveness, Thompson says. Eight weeks is, of course, too short an amount of time to effect major change. “At this point, we are primarily seeing improvements in attention, with less
improvement seen in hyperactivity and impulsivity,” Dr. Mostofsky cautions. “It could be that hyperactive and impulsive behavior will improve with a longer duration of intervention.” Dr. Clark and Thompson give the children a tai chi DVD or—more recently—access to a video practice website. That allows them to continue practicing tai chi form and movement at home, when the eight weeks are up. In the future, Dr. Mostofsky hopes to ramp up his team’s liaison with Baltimore City Public Schools—they’ve worked with three already—to study the effects of mindfulness programs on students in more detail. He’d also like to start up a mindfulness research classroomlaboratory at Kennedy Krieger that could allow for longer-term, ongoing mindfulness intervention studies.
Looking Ahead Dr. Mostofsky hopes his study will help the ADHD community understand how tai chi and other mindfulness interventions can help reduce ADHD symptoms in children and help them become more aware of their behaviors and thoughts. Ultimately, he would like to understand whether and how tai chi, and perhaps other movementand mindfulness-based practices, could best be recommended to children with ADHD as a way for them to learn to control their symptoms while decreasing medication or perhaps even eliminating it completely. Tai chi could be a way to give children with ADHD a chance at an improved, perhaps even medication-free, life. After completing this study, the next step, Dr Mostofsky says, is to see if the changes noted in the children who’ve taken the tai chi class are specific to tai chi, or if they’re also seen in children— either with or without ADHD—participating in more non-specific activities, such as dance or unguided physical recreation.
Along with that, the goal is to study the effects— and the mechanisms in the brain through which those effects are produced—of movement-based mindfulness practice on children with other neurodevelopmental conditions, such as autism and Tourette’s syndrome. At Kennedy Krieger, a team of experts on ADHD is working to better understand the causes of the disorder and to identify interventions that will help children with ADHD succeed in life.
Respect Hands
“I like making the ‘respect hands’ sign,” Dr. Clark says, “because what you’re really doing is respecting yourself.” For the children in his tai chi class, that means beginning to gain some control over their ADHD symptoms.
At the end of every tai chi class, Dr. Clark shows his students how to form their hands into the tai chi sign of respect for one’s opponent. Practitioners place the fist of one hand into the open palm of the other, a nod to the unity of opposites expressed in the “yin yang” concept. “I like making the ‘respect hands’ sign,” Dr. Clark says, “because what you’re really doing is respecting yourself.” For the children in his tai chi class, that means recognizing and respecting their own thoughts and actions and beginning to gain some control over their ADHD symptoms. The children’s progress lets Dr. Mostofsky and his colleagues know that their research is changing lives, even as it happens.
For a full list of current ADHD research studies at Kennedy Krieger, please visit KennedyKrieger.org/ADHD. Clockwise, from left: Dr. Dav J. Clark (in yellow shirt), Wyatt, Kelvan, Dr. Stewart Mostofsky, Sara, research assistant Heather Thompson and Atticus practice tai chi. KennedyKrieger.org/17Gratitude | 7
“I can’t think of a time when I wasn’t interested in architecture. I want to build stuff that will last.” —Dylan
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ime isn’t something Dr. Kathryn Wagner has a lot of—not if she wants her patients to get better.
Dr. Wagner directs Kennedy Krieger Institute’s Center for Genetic Muscle Disorders, which treats children and adults with muscle disorders such as limb-girdle, Becker and Duchenne muscular dystrophies. Muscular dystrophy comes in dozens of forms, depending on the gene affected. In the U.S., approximately 20,000 people, mostly boys, have Duchenne muscular dystrophy, and for them, the disorder is fatal. Dr. Wagner is working to change that, beginning with the patients she’s caring for right now. Founded in 2009, the center—which has a multidisciplinary clinic, a clinical research branch and a laboratory research branch—is one of only a handful of centers in the world providing expert clinical care and seeking new therapies for these disorders. The center sees more than 1,000 patients a year with muscular dystrophy from across the country and around the world. In 2014, it became a Certified Duchenne Center of Excellence. Dr. Wagner divides her time between the center’s clinic and laboratory, working tirelessly to develop new ways to stop muscular dystrophy from destroying her patients’ muscles. She sees patients regularly and leads clinical trials of drugs for muscular dystrophy developed at the center or elsewhere. The center runs about a dozen clinical trials at any given time. Some are large, multicenter pharmaceutical trials involving other research institutions and hospitals. Others take place only at Kennedy Krieger and are the direct result of laboratory research performed at the center.
Dylan, who has muscular dystrophy, visits Kennedy Krieger once a month for checkups, therapy and medicine available only through a clinical trial. He wants to become an architect.
Trial drugs haven’t received final approval from the U.S. Food and Drug Administration, but they are approved for clinical trial, a necessary step in obtaining FDA approval. “With few exceptions, the drugs offered through the clinical trials are the only options available to my patients for slowing the destruction of their muscles,” Dr. Wagner says. Many of her patients take steroids to help preserve muscle strength and function, but the steroids’ effects are limited. Better drugs are needed.
Minding Myostatin
“With few exceptions, the drugs offered through the clinical trials are the only options available to my patients for slowing the destruction of their muscles.” —Dr. Kathryn Wagner, MD, PhD
One new type of therapy being studied in clinical trials for muscular dystrophy involves blocking myostatin, a naturally occurring protein in muscle that keeps muscle growth in check. Dr. Wagner and others working in her field believe that blocking the myostatin in the muscles of a person with muscular dystrophy will keep that person’s muscles stronger for a longer period of time, perhaps even regenerating muscle. In the center’s laboratory, she and her colleagues have shown that blocking myostatin in animal models improves muscle regeneration and decreases the scar tissue that forms in muscles as they break down. The center is currently participating in two trials to test whether blocking myostatin is helpful to boys with Duchenne muscular dystrophy. >>
Above: Dr. Kathryn Wagner meets with Dr. Kenneth Estrellas at Kennedy Krieger’s Center for Genetic Muscle Disorders. Left: A microscopic view of myostatin, a naturally-occurring protein in muscle that keeps muscle growth in check.
KennedyKrieger.org/17Gratitude | 9
And last year, in collaboration with an industry partner, the center launched the first trial of a drug devoted to limb-girdle muscular dystrophy 2I, which predominantly affects the muscles used for sitting and standing. “The first generation of myostatin inhibitors was safe but not all that effective,” Dr. Wagner says. “Our hope is that this current generation will do a better job of knocking down myostatin.”
A Shot of Strength Thanks to all of this research, there’s hope for patients like Dylan, an astute and upbeat 11-year-old with Duchenne muscular dystrophy. Dylan is part of a new clinical trial that’s testing how well one of these second-generation myostatin inhibitors works for boys with Duchenne muscular dystrophy. He received his first dose of the drug in the form of an injection last winter. Much of the important preclinical work leading up to the trial took place in Dr. Wagner’s laboratory.
Dylan demonstrates his walking capabilities for Dr. Kathryn Wagner during one of his monthly checkups.
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“It really is an honor to work with patients with muscular dystrophy. They have a survivor’s mindset, always challenging themselves to overcome obstacles. In spite of these obstacles, they’re very optimistic, and I really enjoy working with them.” —Dr. Kathryn Wagner, MD, PhD, director of the Center for Genetic Muscle Disorders at Kennedy Krieger Institute
“There’s more than a decade of really good science leading up to this trial,” Dr. Wagner says. Dylan has been Dr. Wagner’s patient for the past four years. He walks short distances with ease and lives a fairly typical life—albeit one with daily steroid pills and monthly trips to Kennedy Krieger for blood draws, cardiology checks, movement evaluations, physical and occupational therapy, and injections of the trial drug. At home, Dylan attends school, enjoys zipping around outside on a motorized scooter and is planning on a career in architecture. He has a room full of building models he’s made out of Lego bricks while experimenting with different architectural forms, developing an aesthetic sensibility all his own. “I can’t think of a time when I wasn’t interested in architecture,” he says. He lives in New York City, and loves studying the city’s built environment. He particularly loves buildings with natural light and modern architecture, including just about anything by Frank Lloyd Wright. Diagnosed with Duchenne muscular dystrophy at age 4, Dylan has been treated for the disorder since age 5, first at a hospital in the Midwest for two years, then at Kennedy Krieger. His mother, Catherine, chose Kennedy Krieger because of the strength of its multidisciplinary clinical care and muscular dystrophy research. “Getting treatment and access to clinical trials at Kennedy Krieger—I feel like it’s everything a parent can do,” says Catherine, who has become a lay expert in the disease thanks to her work with the Parent Project Muscular Dystrophy group, which advocates for better funding for muscular dystrophy research. “Because, of course,” she says, “we all want to do as much as we can for our children.”
Dr. Wagner draws inspiration for her work from her patients themselves. “It really is an honor to work with patients with muscular dystrophy,” she says. “They have a survivor’s mindset, always challenging themselves to overcome obstacles.” In spite of these obstacles, “they’re very optimistic, and I really enjoy working with them. “It’s what brought me into the field to begin with,” she explains, “and it’s what motivates me every day in my work.”
Dylan works with Alexander Farnum, a clinical research coordinator at the Center for Genetic Muscle Disorders.
‘Stuff That Will Last’ “A lot of fighting this disease is early intervention,” Catherine says. She and Dylan learned at the clinic that going up and down stairs may be detrimental to Dylan’s muscles, so Dylan doesn’t do stairs anymore. He takes supplements to maintain his health and drugs to protect his heart.
Dylan couldn’t exemplify that courageous optimism any better. As Dr. Wagner researches how to save and build up her patients’ muscles, Dylan learns all he can about architecture so that he can be an architect in the not-too-distant future.
“Getting treatment and access to clinical trials at Kennedy Krieger—I feel like it’s everything a parent can do.” —Catherine, Dylan’s mom
In that way, he’s a lot like Dr. Wagner. “I want to build stuff that will last,” he says.
To learn more about Kennedy Krieger’s Center for Genetic Muscle Disorders, visit its website at KennedyKrieger.org/MuscleDisorders2.
“A little bit of work on the front end of the diagnosis can change the trajectory of the disorder for the better,” Catherine says. “The young boys with muscular dystrophy today are doing amazingly well,” thanks to all of the research that’s gone into keeping them as healthy as possible. Catherine credits Dr. Wagner for her son’s ability to continue walking. “She really knows the intricacies of this disease and how hard it is to combat.”
Above: Dylan and his mom, Catherine Left: Dylan and his mom meet with Dr. Genila Bibat (right), a neurogenetics research associate at Kennedy Krieger.
KennedyKrieger.org/17Gratitude | 11
The Kennedy Krieger Research “Engine”
140+
200+
FACULTY
1 IN 6 CHILDREN
ACTIVE GRANTS
from basic scientists to clinical experts
STUDIES
At Kennedy Krieger Institute, we’re focused on developing life-saving treatments to help children with disorders of the brain, spinal cord and musculoskeletal system achieve their full potential. Our researchers are relentless innovators dedicated to improving children’s lives. Here’s a look at some compelling statistics about the children we serve and the Institute’s progress toward helping them.
80% HUMAN
20%
ANIMAL
HAS A DEVELOPMENTAL DISORDER (12 MILLION CHILDREN)
We’re moving to define disorders according to their
BIOSIGNATURES rather than their signs or symptoms, allowing for precision medicine testing and measurements.
THIS OFFERS EXCITING NEW RESEARCH OPPORTUNITIES TO POTENTIALLY ARREST DEBILITATING CONDITIONS LIKE AUTISM, ADHD AND CEREBRAL PALSY.
National Health Interview Survey-Child, 2011, U.S. Census, CDC MMWR 2003
Lifetime care for those with developmental disabilities increases by
60
$
BILLION EACH YEAR.
Infants and children are understudied in current clinical research trials—fewer than 30% of clinical trials for brain disorders involve infants and children. 12
Stages of Research at Kennedy Krieger Institute
BASIC DISCOVERY
PATIENT RESEARCH
CLINICAL TRIALS
TRAINING & POLICY
KENNEDY KRIEGER HAS PUBLISHED MORE THAN 550 PAPERS SINCE 2015
24,000
We have a track record of important discoveries, including:
UNIQUE PATIENTS & THEIR FAMILIES
SPECIALIZED NIH-FUNDED CENTERS AND CORES
9M INTELLECTUAL $ DISABILITIES 6M CHILD NEUROLOGY RESEARCH $ TRAINING CENTER GRANT 15M NEUROIMAGING
48%
Patient Research
600
500
STUDIES
(PCORI, Simons)
CEREBRAL PALSY ■ ADHD ■ AUTISM ■
500 400
14% Technical Development
INDIVIDUALS
10 YEARS, 2,500 ARTICLES, 50,000 CITATIONS
700
17% Basic Discovery
$
21,000
300
1% Policy 6% Clinical Trials
Development of tests and assessments to diagnose autism in children as young as 6 months old
In the next decade, we look to treat the causes of children’s brain disorders, instead of just the symptoms. cerebral palsy
learning intellectual disorders disabilities
rare ADHD diseases
100 0
Development of life-saving newborn ALD test
concussion autism traumatic dyslexia brain injury
200
14% Reviews
Discovery of Sturge-Weber gene
Kennedy Krieger Institute
Boston Children’s Cincinnati Children’s Hospital of Children’s Hospital Philadelphia Hospital
National Children’s Hospital
Texas Children’s Hospital
Kennedy Krieger is a top-publishing institute in cerebral palsy, ADHD and autism research.
Your support for our research programs, and for the application—in the clinic—of our discoveries in the lab, helps children and families from around the world and is critical to our success. KennedyKrieger.org/17Gratitude | 13
“Our view is that everyone is testable, as long as you have the right tools.” —Dr. Beth Slomine, PhD, ABPP
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even-year-old Garrett lay nearly motionless on his hospital bed in Kennedy Krieger’s inpatient unit.
Only a few weeks before, he’d been playing soccer with his buddies. Then he got sick. His doctor thought it was strep throat and prescribed antibiotics, but Garrett got worse. Within a week, he was comatose and in the pediatric intensive care unit (PICU) at The Johns Hopkins Hospital. Something had caused Garrett’s immune system to go awry, and it was attacking his brain and spine. Doctors worked quickly to keep Garrett alive, but it was four weeks before he could even open his eyes. That was the day, in August 2015, when he was transferred to the inpatient unit at Kennedy Krieger Institute to begin the long process of recovery and rehabilitation. Dr. Beth Slomine, co-director of the Kennedy Krieger Center for Brain Injury Recovery, first saw Garrett when he was in the Johns Hopkins PICU. As his parents wondered if their son would pull through, Dr. Slomine methodically tested Garrett to see how he would respond if she touched his arm, pinched his finger or wafted the scent of ammonia under his nose. Garrett wasn’t responding consistently to touch, pain or smell, but Dr. Slomine noticed that when she tried to interact with him, he would take deeper breaths and move his mouth a little, and his heart rate would increase. It wasn’t much, but it was a good sign.
‘Everyone Is Testable’ When a patient is recovering from a traumatic or acquired brain injury, doctors rely on certain standardized tests of functional independence to assess the patient’s recovery progress. Standard measures like the Functional Independence Measure for Children (WeeFIM) are frequently used by pediatric rehabilitation centers to track a child’s recovery.
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A therapist assesses Garrett’s recovery from a brain injury according to a highly sensitive set of measures developed at Kennedy Krieger by Dr. Beth Slomine.
The problem with those tests is that they don’t measure subtle, clinically important changes in children with very severe impairments. They also aren’t sensitive to meaningful signs of recovery when a child is very young (under 2 years old) or developmentally delayed. Dr. Slomine and her colleagues began developing ways to measure very low levels of cognitive functioning in pediatric brain injury patients in the late 1990s. They started out by identifying the most important signs of recovery in these children, and then, in the early 2000s, used those signs to create a set of four scales—now called the Kennedy Krieger Scales—to measure recovery. Today, the scales are copyrighted, available to rehabilitation centers free of charge, and used around the world. The four scales are the Cognitive and Linguistic Scale (CALS), which measures cognitive and language skills; the Physical Abilities and Mobility Scale (PAMS), which measures lower extremity movement and mobility; the Upper Extremity Motor Scale (UEMS), which measures upper extremity movement; and the Oral Motor Measurement Scale (OMMS), which measures swallowing ability and oral motor skills. When patients are totally dependent on others for care, these scales measure changes that the WeeFIM can’t, by design, detect. That gives doctors, family members and insurance companies clues to a patient’s otherwise unmeasurable progress toward recovery, even if the cause of the patient’s impairment is unknown, as was the case with Garrett. “When you don’t know what’s causing a patient’s impairment, it’s very difficult to make predictions about prognosis,” Slomine says. “All you have to go by is whether the patient is displaying any detectable signs of recovery. “Our view is that everyone is testable, as long as you have the right tools.”
Accurate Tests Indicate Potential Dr. Slomine’s research over the years has shown that early recovery predicts later recovery. “If you can measure that improvement, however slight, you can provide better guidance to families and healthcare providers about what to expect at discharge and in the long term,” she says. If subtle changes aren’t identified early on in recovery, “the potential for recovery may be overlooked, and the patient may miss out on therapies he or she might otherwise have received and benefitted from.” For example, the WeeFIM measures a child’s ability to do things like eat and get dressed. Garrett received the lowest score for just about everything the WeeFIM measured each time it was administered during his inpatient stay at Kennedy Krieger. That might have indicated he was making no recovery. In fact, he was making great strides—it just didn’t register on the WeeFIM. His score on the CALS, which measures things like responding to stimuli and demonstrating visuospatial perception, however, rose from 22 to 33 during his two-plus months as an inpatient at Kennedy Krieger. That told Garrett’s doctors, nurses, therapists and family members that recovery was possible. It also led Dr. Slomine to refer him to Kennedy Krieger’s Specialized Transition Program (STP) for eight months of intensive rehabilitation after inpatient discharge. Garrett attended the STP as if he was going to school, receiving several sessions of intense therapy and participating in modified educational activities every day. Now, Garrett’s back at his old school, where he receives occupational, physical and speech therapies. He uses
Dr. Beth Slomine (far right) meets with colleagues (r to l) Kristy Chao, Beth Cater, Dr. Melissa Trovato, Heather McLean and Dr. Megan Kramer. a walker to get around, and visits Kennedy Krieger for follow-up appointments. He plays adaptive soccer on the weekends and is looking into playing other adaptive sports, too. Last year, Garrett participated in the Baltimore Running Festival, which raises money for Kennedy Krieger. He completed the last 40 yards of the kids’ fun run with a walker. Only a year before that, he was riding the race in a wheelchair, pushed along by his dad, Chuck. Next year, Chuck says, Garrett wants to walk—or maybe even run— the kids’ race on his own. Getting kids like Garrett back into the activities they enjoyed before brain injury is one of the main things motivating Dr. Slomine in her quest to ensure that there’s a measurement tool available for all children with brain injuries. With her work, she’s making it easier to ensure positive outcomes for all pediatric brain injury patients.
To learn more about Kennedy Krieger’s Center for Brain Injury Recovery, visit its website at KennedyKrieger.org/BrainInjuries.
“When you don’t know what’s causing a patient’s impairment, it’s very difficult to make predictions about prognosis. All you have to go by is whether the patient is displaying any detectable signs of recovery.” —Dr. Beth Slomine, PhD, ABPP, co-director of the Center for Brain Injury Recovery, and director of training and neuropsychological rehabilitation for the Department of Neuropsychology 15
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or decades, medicine offered little hope to patients with rare genetic diseases like torsion dystonia and adrenoleukodystrophy.
There were too few patients with any one rare disease to be able to study it thoroughly, and it wasn’t always possible to tell what disease a patient had. But this was just the sort of challenge for Dr. S. Ali Fatemi and members of Kennedy Krieger’s neurogenetics research team to take on. As genetic testing became cheaper, faster and more accurate, Dr. Fatemi, a pediatric neurologist, saw it as the key to solving his patients’ medical mysteries. “If we can nail a disease down to its molecular problem”—at the DNA level—“we can treat patients in a better, more precise way than if we were trying to treat something nonspecific, like a disability,” says Dr. Fatemi, who directs Kennedy Krieger Institute’s Division of Neurogenetics and Moser Center for Leukodystrophies. Leukodystrophies are genetic diseases affecting the brain, spinal cord and, often, peripheral nerves. Each type of leukodystrophy is caused by a specific gene mutation leading to abnormal development or destruction of the myelin sheath—a protective layer of fat that insulates nerve fibers. The children Dr. Fatemi sees have sometimes gone for years without a correct diagnosis.
“When you look at the genes, you’ll discover the disease. Maybe it’ll be one we know of, and then maybe we can treat it. Or, maybe it’ll be a new one.” —Dr. S. Ali Fatemi, MD 16
Dr. S. Ali Fatemi was instrumental in identifying Andrea’s rare disease. Here, Andrea shows Dr. Fatemi how to use a stand-up paddleboard.
Their parents wonder if there’s any hope. Dr. Fatemi and his colleagues don’t just hold out hope. They study their patients’ DNA and find out what’s going on. “When you look at the genes, you’ll discover the disease,” he says. “Maybe it’ll be one we know of, and then maybe we can treat it. Or, maybe it’ll be a new one,” and he and his colleagues will work on finding a treatment. In the last five years, they’ve discovered six new diseases by looking at DNA.
Diagnose Correctly, Then Treat Five and a half years ago, Andrea, now a teenager, landed in Dr. Fatemi’s clinic with what she’d been told by another neurologist was a conversion disorder. For the previous two years, her ability to walk had progressively worsened, her left leg bowing outward because her left foot wouldn’t rest flat on the floor. She’d been advised against medical treatment because, she was told by her doctor at the time, the condition was all in her head, her mother says. Unconvinced, Andrea’s mother took her to Kennedy Krieger. There, they met with Dr. Fatemi and Julie Cohen, a genetic counselor with Kennedy Krieger’s Division of Neurogenetics. Cohen and Dr. Fatemi took into consideration Andrea’s age, symptoms and ancestry, and suspected that a heritable DNA mutation was the real cause of her mobility difficulties. The mutation, which can be traced back more than 300 years to the central European Jewish community, causes a type of torsion dystonia called DYT1, usually treatable if caught early. A DNA test confirmed the diagnosis. “By narrowing down the possibilities, focusing on the DNA and getting to the bottom of Andrea’s situation,” Dr. Fatemi explains, “we were able to identify the correct treatment for her.”
Patients with DYT1 improve dramatically with deep brain stimulation, a surgical procedure. Other forms of dystonia don’t respond to this type of intervention. Just days after undergoing the procedure, Andrea was walking again. Within a few months, she was running, stand-up paddleboarding and—her favorite activity— horseback riding. She occasionally sees doctors at Kennedy Krieger for follow-up. “I know Dr. Fatemi sees my daughter as his patient for life, because whenever she needs him, he is very supportive and is always there to help her with her medical condition,” Andrea’s mother says. “Dr. Fatemi never gives up on her.”
ALD as a Model for Treating Rare Diseases Not much used to be known about adrenoleukodystrophy, also known as ALD. But thanks to the work of Kennedy Krieger neurology research associate Ann Moser, her late husband Dr. Hugo W. Moser, and the current Moser Center team, the center has become a mecca for ALD research, housing the world’s largest clinical database and biorepository for ALD. Now, of all the rare genetic diseases we know about, Dr. Fatemi says, ALD is one of the best-studied. >>
“If we can nail a disease down to its molecular problem, we can treat patients in a better, more precise way than if we were trying to treat something nonspecific, like a disability.” —Dr. S. Ali Fatemi, MD, director of Kennedy Krieger Institute’s Division of Neurogenetics and Moser Center for Leukodystrophies
Dr. S. Ali Fatemi (second from left) meets with genetic counselor Julie Cohen (far left) and research associate Ann Moser (to the right of Dr. Fatemi).
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In the coming year, Kennedy Krieger will participate in three trials for new drugs targeting ALD, and it will be “a prominent—possibly a lead—site for these trials,” thanks to the Moser Center’s extensive experience in working with ALD. For patients with rare diseases, trials are often the only way to receive any sort of treatment. Dr. S. Ali Fatemi talks with Andrea.
“I know Dr. Fatemi sees my daughter as his patient for life, because whenever she needs him, he is very supportive and is always there to help her with her medical condition. Dr. Fatemi never gives up on her.” —Sandy, Andrea’s mother
The ALD model—studying a disease in depth through basic laboratory and clinical research, collecting a vast repository of information and biological specimens, sharing information with other research centers across the country and around the world, and participating in clinical trials for new drugs—is one that Dr. Fatemi wants to see applied to other rare diseases, like fragile X and Rett syndromes. Only a few other research hospitals in the world follow this approach because it requires a lot of resources, he says. Dr. Fatemi currently focuses on ALD and LBSL—short for leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation. LBSL is a newly discovered leukodystrophy not currently studied by any other center in the world. “We decided to study it since it is a potentially treatable disorder,” Dr. Fatemi has found. As for ALD, “It’s the most common type of leukodystrophy, and perhaps the most devastating one,” he explains. “Imagine a perfectly healthy boy who dies within two years of diagnosis. It is hard not to cry every single time we have a conversation with the family of a newly-diagnosed child,” he says. “It is heartbreaking.”
Andrea (left) and her sister, Natalie, run their own soap-making business, Scrubbles Bubbles, from their home. They shape the soaps like desserts. 18
Go Big and Conquer Identifying a rare disease and determining potential treatments for it is painstaking work, but it means everything—life itself—to Dr. Fatemi’s patients. Sometimes, the treatments they and other rare disease researchers find for one disease turn out to be useful in treating other diseases—both rare and common—like cerebral palsy, Dr. Fatemi says. The trick, he points out, is that you need to have a lot of patients to study—more than he can find in just the mid-Atlantic area. Collaborating with centers around the world to have a larger sample size to study and using mobile, wearable technologies to collect information about patients living far away from clinics is “the next new thing,” he says. His vision is a worldwide network of doctors and researchers for every rare disease, like ALD Connect—a global ALD consortium he helped found a few years ago between Kennedy Krieger and several research universities across the world to share information on ALD. Some might find this a daunting task, but not Dr. Fatemi and his team. It may take a world’s worth of research just to halt or cure one child’s disease, but when that child starts living a typical life—walking, laughing, going to school, growing up—he and his colleagues know they’re headed in the right direction.
To learn more about the Moser Center for Leukodystrophies, visit its webpage at KennedyKrieger.org/MoserCenter.
“Imagine a perfectly healthy boy who dies within two years of diagnosis. It is hard not to cry every single time we have a conversation with the family of a newly-diagnosed child. It is heartbreaking.” —Dr. S. Ali Fatemi, MD
Why Give? Thanks to you, our donors, we were able to treat more than 24,000 patients in 2016. Your generosity allowed our faculty members to diagnose dozens of rare diseases—some never before identified—and enabled our patients and others to participate, collectively, in clinical trials that offer the possibility of lifesaving new treatments and interventions. Your kindness means that our patients receive not only the best care possible but also a reason to hope for a better future, and the chance to reach their full potential. Thank you.
800+ Di v e r s e
171 Fairmount 174 High School 64 LEAP
disorders diagnosed
& treated
56 Montgomery County 93 Type II programs (Public school partnerships: Anne Arundel, Prince George’s counties; Baltimore City)
1 in 6 children Has A Developmental disorder (12 million children)
558
patients served in 2016
63% ages 4-14
15% ages 15-20
9% ages 21+
13% ages 0-3
Students served by our school programs
75+ Clinical Programs
National Health Interview Survey-Child, 2011, U.S. Census, CDC MMWR 2003
24,000
140 527
+
Faculty & research faculty members
STUDENTS SERVED BY OUR trainees SCHOOL in 14 disciplines PROGRAMS
926
Clinical trials
38 Drug trials 12 Device trials 18 Other trials KennedyKrieger.org/17Gratitude | 19
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