Great promise for revolutionary new therapies for children with cerebral palsy

TORONTO, April 26, 2012 /PRNewswire/ – CIBC (CM: TSX) (CM: NYSE) and Holland Bloorview Kids Rehabilitation Hospital are thrilled to announce an innovative clinical research study in robotics therapy for children with cerebral palsy.  Cerebral palsy is the most common childhood physical disability in Canada, affecting approximately one in every 300 Canadian children.

“There is a lot of excitement about the innovative use of robotics in treatments and therapies for children with cerebral palsy and other neurological disorders. We are tremendously grateful to our partners for supporting this exciting development in research at Holland Bloorview.  This research holds great promise for revolutionary new therapies for children with cerebral palsy,” said Dr. Virginia Wright, Scientist, Bloorview Research Institute.

The exciting two-and-a-half year clinical research study, funded by CIBC with a $500,000 donation and co-led by Dr. Darcy Fehlings and Dr. Virginia Wright, is the first known randomized trial to evaluate the impact of robotic assisted gait training for children with cerebral palsy.  This study, will allow Holland Bloorview to develop evidence-informed best practices and guidelines for clinical use of robotic therapy, specifically with the Pediatric Lokomat^® Pro, for children with different severities of cerebral palsy.

“At CIBC we care about what matters – especially kids, cures, and community. If this research finds news therapies for kids with disabilities then our Miracle Day aspiration – of helping kids who need it the most – will be realized,” said Geoff Belsher, Managing Director and Group Co-Head, Wholesale Banking, CIBC.

CIBC’s donation is funding clinical research using a state-of-the-art robotic device known as the Pediatric Lokomat^® Pro. This specialized equipment was generously donated to Holland Bloorview by the THREE TO BE foundation and its supporters. The innovative gait training device supports a child to walk upright while using robotics to move the child’s legs in a way that simulates a natural walking pattern.  A virtual reality screen is built-in to the device so that kids can choose a character to move in sync with them.  The more the child actively engages in walking, the greater the motor learning effect is thought to be.  The lokomat’s biofeedback and virtual reality systems give a motivational and fun environment with direct, real-time feedback to the child, parent and therapist on performance.

Robotic therapy has the potential to transform treatment for children with cerebral palsy by making walking therapy more stimulating and engaging, more effective, and more inclusive for children with different walking abilities and goals.

With the incredible support of CIBC, THREE TO BE and KRG Children’s Charitable Foundation, Holland Bloorview will be conducting a leading edge clinical research trial with the lokomat.  This is a unique $1 million partnership between three foundations and a bank working together to help create a world without limits for children with disabilities.

About CIBC:
CIBC is committed to supporting causes that matter to our clients, employees and our communities. We aim to make a difference in communities through corporate donations, sponsorships and the volunteer spirit of employees. With a strategic focus on Kids, Cures and Community, and employee commitment to causes including the Canadian Breast Cancer Foundation CIBC Run for the Cure, the CIBC Children’s Foundation and United Way, we are investing in the social and economic development of communities across the country. In 2011, CIBC contributed over $35 million to charitable and non-profit initiatives in Canada to support national, regional and local organizations. To learn more, visit www.cibc.com

About Holland Bloorview Kids Rehabilitation Hospital Foundation
Holland Bloorview Kids Rehabilitation Hospital Foundation raises funds in the community for Holland Bloorview Kids Rehabilitation Hospital. Holland Bloorview is Canada’s largest children’s rehabilitation hospital. The hospital pioneers treatments, technologies, therapies and real-world programs that give children with disabilities the tools to participate fully in life. For more information, please visit: www.hollandbloorviewfoundation.ca

SOURCE  CIBC

Image with caption: “Wesley Magee-Saxton, age 12, walks using the help of the Pediatric Lokomat® at Holland Bloorview Kids Rehabilitation Hospital as they launch a revolutionary clinical trial in robotic therapy benefiting children with cerebral palsy and other neurological disorders. (CNW Group/CIBC)”. Image available at:  http://photos.newswire.ca/images/download/20120426_C9528_PHOTO_EN_12763.jpg

©2012 PR Newswire. All Rights Reserved.

Five-year-old Lauren’s cerebral palsy used to make eating meals an ordeal, going to bed a challenge, and crawling an impossibility.

But her new baclofen pump implant helps loosen and tone her muscles, making daily activities much easier to manage for Lauren and her family.

“She can crawl upstairs now, allowing my 71-year-old mother… to be able to safely get Lauren upstairs and to bed,” says Lauren’s mother, Sandy Tierney. “She sleeps better, naps less and is happier now that her body is more predictable and responds to her.”

Lauren and her parents have been participating in occupational therapy professor Ruth Benedict’s ongoing study to measure the functional effects of the baclofen pump for children with cerebral palsy (CP).

Compared to injections and pills that wore off or caused fatigue, the pump’s slow and measured release of baclofen — a drug derived from a mammalian neurotransmitter acid — gives Lauren the consistent muscle tone she needs to go about her life more comfortably and quickly.

“I don’t have to take the pill any more, and then I can have breakfast quicker,” Lauren says, as relayed by her mother. “It helps me get up the stairs more easily, and I’m not so tight.”

Benedict is studying how the pump and subsequent therapies affect functioning, care, health, well being and participation in home and community life for clients with CP as well as their caregivers.

Health care providers are putting a lot of resources into supporting children who receive these interventions, so knowing that it is effective is imperative, Benedict says.

“Certainly there’s enough evidence out there right now to show that it is effective enough in terms of reducing (muscle) tone in these children, but there’s not enough evidence out there showing what the implications are for care giving, and for the child’s function,” she says. “That’s what we’re hoping to show — that not only is there a physiological change in the child, but that the physiological change has implications for the child’s function and for the caregivers ability to care for the child.”

Benedict’s research team has already collected pre-intervention data on 20 client-caregiver pairs, six-month post-surgery data on more than half the pairs, and two-year data on five pairs.

Participants fill out initial questionnaires about their health, activities and spasticity management and other effects of cerebral palsy on their daily activities. They meet with the research team a total of four times, once before and three times after the surgery. Team members interview participants about their goals and concerns regarding the treatment and record them as they perform typical activities while wearing equipment that monitors their movements and energy exertion.

“Thus far, the general perception is that there does seem to be a change, at least in some areas of care giving, but we’ll have to wait until we see and analyze all the data to know for sure,” she says.

CP is one of the most prevalent childhood disabilities, and an expensive one — a 2003 CDC report estimates that the cost during one person’s lifetime can be more than $900,000.

Benedict hopes to show that the functional benefits of the pump, including caregiver time and energy, outweigh its side effects and financial cost, she says.

She also expects to prove what Tierney hopes for — that the pump will allow Lauren and other children with CP to get a much better return from life-long therapy with occupational therapists and other health care professionals.

“I strongly believe that if we want access to these knowledgeable and highly skilled professionals, we need to help in the information learning and training process,” Tierney says. “Participating in research is for our benefit as well as others.”

SOURCE  Detroit Medical Center; Wayne State University

Findings released “indicate that it is possible to identify neuroinflammation at the time of birth and to treat it using anti-inflammatory agents coupled with nanodevices,” says Dr. Roberto Romero, Chief of the Perinatology Research Branch, NICHD/NIH

DETROIT, April 18, 2012 /PRNewswire-USNewswire/ — Researchers at the Perinatology Research Branch of the National Institutes of Health, housed at the Wayne State University School of Medicine and the Detroit Medical Center, have demonstrated that a nanotechnology-based drug treatment in newborn rabbits with cerebral palsy (CP) enabled dramatic improvement of movement disorders, and the inflammatory process of the brain that causes many cases of CP. The findings strongly suggest that there may be an opportunity immediately after birth for drug treatment that could minimize CP.

(Photo: http://photos.prnewswire.com/prnh/20120418/DC90035)

The study is the first to show that an anti-inflammatory drug delivered with a nanodevice can dramatically improve the symptoms of CP in an animal model.

The report, “Dendrimer-Based Postnatal Therapy for Neuroinflammation and Cerebral Palsy in a Rabbit Model,” will be released tomorrow in the prestigious journal Science Translational Medicine, published by the American Association for the Advancement of Science.

“The key finding of this work is that early identification of neuroinflammation allows postnatal treatment,” said Roberto Romero, M.D., D.Med.Sci., Chief of the Perinatology Research Branch of the NIH and an author of the study. “This suggests that there is a window of opportunity to prevent cerebral palsy.”

Cerebral palsy is a disorder of the developing brain that affects motor skills and muscle coordination, often not diagnosed until the age of two or three years in children. The United Cerebral Palsy Foundation, a national advocacy and support group, estimates that 764,000 children and adults in the United States have CP. According to the U.S. Centers for Disease Control and Prevention (CDC), 100,000 babies born in the U.S. develop CP annually. A 2009 report by the CDC indicated the prevalence of the condition at 3.3 per 1,000 births. Worldwide, the CDC estimates the prevalence of CP births to range from 1.5 to 4 for every 1,000 births.

Risk factors for the condition include low birth weight and premature birth. Children born before the 32nd week of pregnancy are at high risk for developing CP. Intrauterine infection and/or inflammation is a major risk factor for CP.

Microglia – immune cells in the brain – play an important role in remodeling and growth during fetal and postnatal periods. Activation of these cells can cause an exaggerated inflammatory response, leading to brain injury and CP. Treatment is problematic because inflammation and the resulting injury can be spread throughout the brain’s white matter. Transporting drugs across the blood-brain barrier also represents a challenge.

The PRB team hypothesized that it was possible to deliver a drug using a tiny device (or nanodevice) that would cross the blood-brain barrier and target the activated cells in the brain involved in neuroinflammation (microglia and astrocytes).

The researchers used a rabbit model of congenital CP because it replicates the type of neuroinflammation found in human brains and the resulting motor deficits observed in children with CP. The method consisted of exposing fetal rabbits to endotoxin (a component of bacteria). Endotoxin induced inflammation of the fetal brain but did not induce the onset of labor. When the rabbits were born, they had great difficulties walking or hopping. The experiment consisted of treating affected rabbits intravenously with either a saline solution, a drug known as NAC (N-acetyl-L-cysteine) or a dendrímer coupled with NAC, also known as a D-NAC conjugate. Rabbits with CP treated with D-NAC on the first day of life showed a dramatic improvement and, within five days, were able to walk and hop, which those without treatment were not able to do. Rabbits treated with the NAC conjugate also showed a higher neuron count and lower evidence of inflammation compared to untreated animals.

NAC is an antioxidant and anti-inflammatory agent. It is being explored in several ongoing clinical trials to test its potential in autism spectrum disorders, pregnant women for the treatment of maternal and fetal inflammation and Alzheimer’s disease. Dendrimers are synthetic biomimics of globular polymers of the amino acid alanine. Researchers are exploring their use as a vehicle to target drug delivery, a science known as nanotechnology.

The authors believe that conjugating NAC with dendrimers allows delivery of this drug directly to the cells involved; hence, the greater effectiveness of this approach.

“One of the challenges of the 21st century is to rebuild brains injured during fetal or neonatal life, and to prevent not only cerebral palsy, but also other brain disorders,” Dr. Romero said.

The CDC estimates that the lifetime costs to care for a person with CP amounts to nearly $1 million (in 2003 dollars). The estimated combined lifetime costs for all Americans born with CP in 2000 is expected to total $11.5 billion in direct and indirect costs.

The therapy described by the PRB researchers also holds promise for possible future treatments of some neurological disorders, including multiple sclerosis. The brain, for the most part, can be divided into gray and white areas. Neurons are located in the gray area, and the white parts are where the neurons send their axons — similar to electrical cables carrying messages — to communicate with other neurons or muscles. Oligodendrocyte cells manufacture a cholesterol-rich membrane called myelin that coats the axons. The myelin’s function is to insulate the axons, much like the plastic coating on an electrical cable. In addition, the myelin speeds communication along axons and makes that communication much more reliable. Patients with multiple sclerosis display neuronal loss and myelin abnormalities that reduce the myelin coating.

The PRB team found that D-NAC therapy also improved the production of myelin and reduced the neuroinflammation associated with the loss of myelin. In fact, by the fifth day after treatment with D-NAC, the CP rabbits demonstrated a significant increase in myelin that nearly matched healthy control animals.

While still in preclinical testing in animals, the dendrimer-drug conjugate shows promise for postnatal treatment of babies suspected of having CP.

“This is an exciting breakthrough and it certainly points toward new hope for those affected by cerebral palsy,” said Rangaramanujam M. Kannan, Ph.D., a chemical engineer and a member of the PRB research team and an author of the study. “We found that the administration of the anti-inflammatory agent coupled with the dendrimers allowed the drug to not only cross the blood-brain barrier — but also to target the cells that cause the neuroinflammation in CP. Of course, this approach and these compounds are not yet approved for testing in humans, and further studies are required to find the optimal dose, duration of treatment and establish safety. More questions need to be answered, but the potential is immense.”

“The use of a rabbit model is a unique aspect of the work, since this model mimics the phenotype of CP as seen in humans. This also illustrates the potential of research collaborations across disciplines in advancing and translating novel technologies for the treatment of debilitating childhood disorders,” said Dr. Sujatha Kannan, a pediatrician and first author of the study.

Dr. Kannan stated that the work was possible by the development of an animal model of cerebral palsy, the implementation of molecular imaging to detect neuroinflammation at the time of birth, and the coupling of the nanodevices (dendrimers) with NAC. The significance of the work is that it opens avenues for the treatment of neuroinflammation, a mechanism of disease not only for cerebral palsy, but for other conditions such as meningitis, encephalitis, multiple sclerosis, etc.

“This is tremendous recognition of the research breakthroughs and the power of the partnership between Wayne State University, the Detroit Medical Center and the Perinatology Research Branch,” said Valerie M. Parisi, M.D., M.P.H., dean of the Wayne State University School of Medicine. “This study has the potential to pull back a curtain that has shrouded a medical challenge not just in relation to cerebral palsy, but with other conditions that affect millions around the world.”

DMC President and CEO Michael Duggan said that the publication of the PRB study marked “a hugely important step forward in the decades-old struggle to protect infants and their parents from the immense suffering caused by cerebral palsy.

“As a healing institution with a passionate commitment to medical research, having Dr. Romero’s PRB team working on our campus daily for the past 12 years has been extraordinarily gratifying,” Duggan said. “For all of us at the DMC, this is a deeply rewarding moment.”

The Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health at Wayne State University is located in the Detroit Medical Center’s Hutzel Women’s Hospital and in basic science laboratories in the WSU C.S. Mott Center. The PRB is strategically located to serve a high-risk population that requires the full spectrum of services the branch offers. The branch has produced groundbreaking research and cared for more than 20,000 mothers in Detroit.

About Detroit Medical Center www.dmc.org

The Detroit Medical Center includes DMC Children’s Hospital of Michigan, DMC Detroit Receiving Hospital, DMC Harper University Hospital, DMC Huron Valley-Sinai Hospital, DMC Hutzel Women’s Hospital, DMC Rehabilitation Institute of Michigan, DMC Sinai-Grace Hospital, DMC Surgery Hospital, and DMC Cardiovascular Institute. The Detroit Medical Center is a leading regional healthcare system with a mission of excellence in clinical care, research and medical education.

About Wayne State University www.wayne.edu

Wayne State University is a premier urban research institution offering more than 400 academic programs through 13 schools and colleges to nearly 32,000 students. Its School of Medicine is the largest single-campus medical school in the nation with more than 1,200 medical students. In addition to undergraduate medical education, the school offers master’s degree, Ph.D. and M.D.-Ph.D. programs in 14 areas of basic science to about 400 students annually.

Editor’s Note: Physicians are available for interviews. For photos, video, b-roll and bios, visit: www.dmc.org/cp

©2012 PR Newswire. All Rights Reserved.

Gai
McMichael, MPhil
Research Scientist
Cerebral Palsy Research Group
Robinson Institute

 Professor Alastair H MacLennan AO,
MB,ChB, MD, FRCOG, FRANZCOG,
Discipline of Obstetrics & Gynaecology,
The University of Adelaide, AUSTRALIA

It has been seen that increasingly newborns are diagnosed with cerebral palsy. This is the reason that obstetricians and neonatal specialists in Australian hospitals have been asked to take steps so that newborns are not born with cerebral palsy.

Cerebral palsy affects 400 Australian children and every child’s condition differs from other in terms of severity. An Australian and international research has also been conducted on cerebral palsy and children.

Researchers have concluded that if a mother is given magnesium sulphate before delivery then 33% risk get reduced. However, it is said that the condition is the most beneficial for children, who born before 30 weeks.

“The implementation of these guidelines has the potential to save the lives of, or minimize cerebral palsy risks in up, to 147 Australian babies each year”, said researchers.

The doctors think that if a mother is given magnesium sulphate then they can save 140 children every year from getting affected with cerebral palsy. Professor Nadia Badawi from the Cerebral Palsy Alliance said that doctors are right that magnesium sulphate reduces the risk.

Obstetrics Professor Caroline Crowther applauded the research and was of the view that it is the one of a kind research which has proved that magnesium sulphate is effective in bringing down the number of cerebral palsy cases.

Caroline affirmed that they also recommend doctors to give the dose to women before delivery, but they seen that the advise is underused. It is happening due to the shortage of staff. In addition, it has also been found that magnesium sulphate also has its cons.

Professor Michael Chapman, who is owner of the School of Womens’ and Children’s Health at the University of New South Wales, was of the view that it can gift your hypertension and can cause low blood pressure.

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The National Science Foundation (NSF) has awarded a $640,000 grant to fund research at Arizona State University (ASU), Tempe, that aims to better understand the sensory and cognitive connections between the brain and the hands. The research collaboration between Marco Santello, PhD, an ASU professor of biomedical engineering, and Columbia University, New York, New York, scientist Andrew Gordon, PhD, could benefit people with neurological disorders such as Parkinson’s disease and cerebral palsy and those who need prosthetic hands.

Santello and Gordon, who is a professor of movement sciences and the movement science program coordinator at Columbia,  are seeking to determine the neural mechanisms that control learning and planning of the grasping and manipulation of objects. They’re examining the visual cues people use to assess object properties before they grasp or otherwise manipulate objects. In addition to using cues such as object shape or density, people often use memory of similar past actions.

Santello’s focus is on neural control of the hand and the workings of senses such as vision and touch. By manipulating these senses in people with normal brain, hand, and muscle functions, Santello studies what causes the performance of an action that is easy under normal conditions to become difficult. This allows him to identify what impact a specific sense has on how the brain controls the hands.

In his experiments, he imposes sensory deficits on test subjects, using goggles to block vision at selected times during the object manipulation to interfere with the subjects’ abilities to learn and execute grasping tasks. “We want to understand what aspects of visual feedback help the brain to successfully control grasping of an object and store a memory representation of that action,” he explained.

Gordon’s research centers on cerebral palsy. His related collaborative work with Santello focuses on cognitive aspects of the interaction between the brain and the hands, assessing the information the brain gains and processes from sensing the shapes of objects and exploring the role of memory of past actions.

Knowledge gained by such research can also be applied to improving neuroprostheses. Current technology is able to provide sophisticated artificial hands, but controlling the hands remains a challenge.

“The more we understand about the high-level processing that the brain has to go through to plan an action, the closer we will be to building more intelligent prosthetic systems that are capable of more human-like performance,” Santello said.

Staten Island Advance Photos/ Irving SilversteinDr. Zaghloul Ahmed uses a device to send a magnetic pulse to the brain – similar to an MRI – while simultaneously sending electrical signals to the desired muscle group and spinal cord. The treatment aims to help those with cerebral palsy, like Christopher Neves of Charleston, increase mobility.

STATEN ISLAND, N.Y. — Christopher Neves describes himself as someone who doesn’t know the meaning of the word “quit.”

Since birth, the 30-year-old Charleston resident has coped with cerebral palsy, a neurological disorder that affects movement. Despite undergoing several surgeries, he uses a wheelchair to get around and has limited mobility in his arms.

But it hasn’t stopped Neves from being optimistic that he will one day walk and “make his mark on the world.” When he heard of a new study at the College of Staten Island (CSI) that may be able to help patients like himself with mobility, he quickly signed up.

“I want a better quality of life. I want to be more independent,” the CSI communications major said. “Some people would be happy to settle. I’m not happy settling.”

Dr. Zaghloul Ahmed, an associate professor in the college’s Department of Physical Therapy, created the PathMaker Neuromuscular Treatment System, a City University of New York (CUNY) trademarked therapy that uses electrical and magnetic stimulation to improve mobility in those with cerebral palsy, stroke and spinal cord injuries, all of which originate in the brain.

Dr. Ahmed previously conducted trials on mice using the same technology. The animal study, funded by the state Health Department and CUNY, featured 14 mice with spinal cord injuries; seven received the treatment and seven did not.

“The mice with the spinal cord injury could not walk as normal,” Dr. Ahmed said. “And after the treatment, they walked significantly better than the ones that didn’t get treated.”

WEAK SIGNAL

He began his human trials  –  funded by a $250,000 BioAccelerate NYC Prize for research  –  in October. Dr. Ahmed explained that when a person moves, the brain generates a signal that it sends down the spinal cord and to the appropriate muscle. But when someone has a brain or spinal cord injury, the signal is weakened and the muscle doesn’t respond correctly.

His system aims to strengthen these neuromotor connections and make the muscles more responsive. During treatment sessions held three times a week for six weeks, Dr. Ahmed uses a device to send a magnetic pulse to the brain  –  similar to an MRI
–  while simultaneously sending electrical signals to the desired muscle group and spinal cord.

“With precise timing, the signals will reach a junction at the spinal cord, where they all meet, and it seems to strengthen the connection between the brain, spinal cord and muscle,” he said.

“After we stop the signals and remove all these stimulators, the brain becomes effective itself and can generate muscle action, even with the injury,” he continued.

“It’s like teaching and strengthening the brain.”

During a recent session, Dr. Ahmed placed electrodes for the electrical stimulation along Neves’ right arm and spine. He then held a device to his head to deliver the painless magnetic pulse as he instructed Neves to move his arm in varying ways to teach the brain to efficiently move the muscles.

“My right arm was kind of tight and not as flexible. It was difficult to touch my thumb to my fingers,” Neves commented. “Now, I’m able to lift the arm up higher and my thumb moves better.”

Neves performs dexterity and stamina tests, such as placing pegs in a board, to measure his progress. When he first started, it took more than  three minutes to complete the task; now it takes a minute-and-a-half.

This is evident in the dexterity and stamina tests Neves performs after their sessions. One has him placing pegs in a board. When he first started, it took more than three minutes to complete the task; now it takes a minute-and-a-half.

“(Dr. Ahmed’s) given me hope,” said Neves, who wants to have the therapy done on his left arm and legs. “I want to live a normal life and just be recognized as ‘Chris,’ not as someone with a disability.”

STROKE SUFFERERS

Timothy Poore of Brooklyn suffered a stroke in August, which, he said, “took out my whole left side.” Used to an independent lifestyle, he now uses a cane and has trouble with everyday tasks like turning pages in the newspaper, cutting food and brushing his teeth.

When the 59-year-old learned of the CSI study from one of his physical therapists, he decided to apply for it. Dr. Ahmed began by using the stimulation on his left arm, which Poore described as “just heavy” following the stroke. After a week, he noticed small improvements.

“I can move my hand up higher and was able to turn the newspaper pages with my left hand,” he reported. “That was something I wasn’t able to do since August.”

Dr. Ahmed has worked with four cerebral palsy and two stroke patients since his human study began, and has been approved for a total of 94 subjects.

He is looking for more participants; currently, the study is open to those ages 21 and up, although he hopes to include younger individuals in the near future. Additionally, Dr. Ahmed has applied to the Institutional Review Board at CUNY to start a spinal cord injury study later this year.

The studies, he said, have the potential to lead to a federal Food and Drug Administration trial, which could make his system more widely available.

“So far, the preliminary results have been nice,” Dr. Ahmed observed, noting, “Overall when we finish this, it can lead to a device that we can have in a clinic and everyone can apply it to their patients.”

Andrea Boyarsky is the Health editor for the Advance. She may be reached at boyarsky@siadvance.com.

An electrifying study

Dr. Zaghloul Ahmed is conducting research utilizing the PathMaker Neuromuscular Treatment System, a therapy that uses electrical and magnetic stimulation to improve mobility in individuals with cerebral palsy or who have suffered a stroke.

Who can apply
The study is currently open to those age 21 and up.

Where it’s held
The College of Staten Island
2800 Victory Blvd., Willowbrook

More information
917-776-7980
zaghloul.ahmed@csi.cuny.edu