A shared goal to raise awareness and develop better treatments for neonatal-onset epilepsy has brought Baylor College of Medicine researchers together with three U.S. families: Jim and Tina Thompson of Iowa, Carla and Bryan Forbes from Massachusetts, and Jim Johnson and Scotty Sims in Colorado. Each couple has a child who suffered his or her first seizure within hours of birth. Those seizures continued through long stays in local neonatal intensive care units where standard treatments were unsuccessful.
Extensive diagnostic workups did not find answers, and each family waited years before the gene causing their child’s seizures could be identified. The parents subsequently helped found or lead different non-profit organizations supporting research on their children’s illnesses, including a new U.S.-wide study called Early Recognition of Genetic Epilepsy in Neonates (ERGENT).
ERGENT, led by Dr. Edward C. Cooper, associate professor of neurology, neuroscience and molecular and human genetics at Baylor College of Medicine, seeks to increase awareness of neonatal genetic epilepsy while testing new tools for identifying the newborns at highest risk for this condition.
Along with co-investigators Dr. John J. Millichap of Ann & Robert H. Lurie Children’s Hospital in Chicago and Dr. Tammy Tsuchida of Children’s National Medical Center in Washington, D.C., Cooper and his colleagues have created a program that provides free-of-charge genetic testing to babies who have features suggestive of a genetically-caused epilepsy.
“Babies with specific genetic causes of epilepsy are less common than those whose seizures are caused by injury, so, unfortunately, this diagnosis is often considered later than is optimal,” Cooper said. “Our goal is to be able to pinpoint features that allow doctors to identify babies at risk soon after birth. This will help us develop and test precision treatments that target the underlying genetic mechanisms and to begin such treatment faster.”
Babies can be referred by medical professionals to ERGENT from anywhere in the United States. Any medical provider may contact ERGENT using a brief online form. If a patient is eligible (and parents provide consent), the study provides testing for more than 180 genes. Results are returned to the treating physician and family approximately two weeks after serum collection.
“Evidence suggests that babies with genetic epilepsy may benefit from specialized treatments that are already available,” said Tsuchida, an associate professor of neurology and pediatrics at George Washington University School of Medicine and Health Sciences. “Newer treatments are being developed now, including both drugs previously used in adults and newer compounds tailored to specific types of genetic epilepsy. These hold promise but remain untested.”
Millichap, an associate professor of pediatrics and neurology at Northwestern University Feinberg School of Medicine, said, “Novel laboratory techniques are available for identifying compounds that treat a patient’s specific type of genetic epilepsy. Our group of collaborators is working to make early diagnosis and testing more available to maximize the potential benefits of these new treatments.”
ERGENT is funded by the Jack Pribaz Foundation, the KCNQ2 Cure Alliance and the FamilieSCN2A Foundation, all nonprofit organizations led by the parents of children with neonatal onset genetic epilepsies.
For more information on entry criteria for patients, go to the ERGENT site or contact email@example.com.
Source: Baylor College Medicine
A small population of brain cells deep in a memory-making region of the brain controls the production of new neurons and may have a role in common brain disorders, according to a study from scientists at the University of North Carolina School of Medicine.
The scientists, who published their work in Neuron, showed that “mossy cells” in the hippocampus regulate local stem cells to control their production of new neurons, which is important for normal learning and memory, stress response, and mood regulation. Such neurogenesis in the adult brain is disrupted in many common conditions including Alzheimer’s disease, depression, anxiety, schizophrenia, traumatic brain injury, and some forms of epilepsy.
In a new study in mice, researchers have identified a key protein involved in the irregular brain cell activity seen in autism spectrum disorders and epilepsy. The protein, p53, is well-known in cancer biology as a tumor suppressor.
The findings, reported in the journal Human Molecular Genetics, will open new avenues for understanding the factors that contribute to these developmental disabilities, said Nien-Pei Tsai, a University of Illinois professor of molecular and integrative physiology who led the new research.
“Under physiologically normal circumstances, neurons are able to readjust their excitability: the strength at which neurons are firing,” Tsai said. “But in autism spectrum disorders, such as Fragile X syndrome, and in epilepsy, you see higher levels of excitability. Our brains need a baseline for neurons to return to after higher or lower neuron excitability. If the neurons can’t return to a normal range, then the baseline is reset outside of a normal range.”
This affects both behavioral characteristics and cognitive functioning, he said.
Exciting new research that involves using a protein in worms to suppress seizures, could spell hope in the future for thousands of people with epilepsy.
Scientists at University College London (UCL) have used a chemical found in worms to reduce seizure activity in the brains of epileptic rats. The chemical produces a protein that quietens down brain activity when glutamate levels build up causing neuronal excitement in the brain.
The chemical is delivered into the brain by injecting it through the skull inside a harmless virus. Using a technique called gene therapy, this enables the worm DNA to spread throughout the brain.
Great hope for the future
Epilepsy Society’s medical director Professor Ley Sander described the new technique as very promising but cautioned that there was still a long way to go before the technique could be safely used in humans.
‘This is a very exciting piece of work offering great hope in the future for people with focal epilepsy that does not respond to conventional treatment. Focal epilepsy starts in a specific area of the brain and where that area can be pinpointed, it is sometimes possible to remove the focal point through brain surgery. But this is possibile if it is in an area of the brain that will not compromise essential functions such as language and movement.
‘Modifying the excitability of nerve cells by introducing a targeted ‘virus’ that will not infect a nerve cell but instead deactivate the seizure, may offer a real alternative to surgery. It also has the advantage of preserving the functional areas of the brain.
‘There is still a long way to go. At the moment results have only been shown in animal models and it is important that this is now translated into humans.
‘But in the future, this type of gene therapy could be used in parts of the brain which are critical for cognitive functions and movement and may also be used where seizures occur in multiple parts of the brain.’
Epilepsy Society works as part of a unique arrangement with UCL and the National Hospital for Neurology and Neurosurgery. Professor Sander said that research into gene therapy could really benefit discoveries made through the charity’s genomic sequencing programme.
‘As we identify genes that are contributory to epilepsy, new gene therapy techniques will allow our colleagues to find ways to engineer them, either switching on or off activity as required. This holds great promise for people with epilepsy.’
Available on NHS in future
If the chemical from worms induces the same response in humans as in rats, the UCL research team hopes a new treatment could be available on the NHS within 10 years.
VIDEO LINK TO WATCH PROF. MATTHEW WALKER TALK ABOUT GENE THERAPY AND EPILEPSY HERE
The research is published in the journal Nature Medicine.
A new line of human stem cells shows promise for one day advancing treatment for epileptic seizures. As reported in STEM CELLS Translational Medicine (SCTM), the cells are designed to deliver adenosine – which calms down overexcited neurons and protects them from damage — to the central nervous system (CNS). The research was conducted by scientists at the University of Bonn and the Central Institute of Mental Health (CIMH) in Mannheim.
Adenosine is a powerful regulator that helps the body maintain its inner balance. When an injury occurs to the CNS, it releases high levels of adenosine, which calms down the overexcited neurons and alleviates neurological damage caused by stroke, trauma, reduced oxygen, pain and, in particular, epileptic seizures. “But attempts to systemically deliver adenosine to needed areas in the CNS during a crisis have been hampered by adenosine’s fast metabolic breakdown, the inability to sufficiently permeate the blood-brain-barrier and serious side effects of such cardiac suppression,” said Philipp Koch, M.D., of the Hector Institute for Translational Brain Research at the CIMH. Dr. Koch headed up the study described in SCTM, which was conducted at the Institute of Reconstructive Neurobiology of the University of Bonn Medical Faculty together with Dr. Oliver Brüstle.