New Cell Therapy Improves Memory and Stops Seizures Following TBI

Researchers from the University of California, Irvine developed a breakthrough cell therapy to improve memory and prevent seizures in mice following traumatic brain injury. The study, titled “Transplanted interneurons improve memory precision after traumatic brain injury,” was published in Nature Communications.

Traumatic brain injuries affect 2 million Americans each year and cause cell death and inflammation in the brain. People who experience a head injury often suffer from lifelong memory loss and can develop epilepsy.

In the study, the UCI team transplanted embryonic progenitor cells capable of generating inhibitory interneurons, a specific type of nerve cell that controls the activity of brain circuits, into the brains of mice with traumatic brain injury. They targeted the hippocampus, a brain region responsible for learning and memory.

The researchers discovered that the transplanted neurons migrated into the injury where they formed new connections with the injured brain cells and thrived long term. Within a month after treatment, the mice showed signs of memory improvement, such as being able to tell the difference between a box where they had an unpleasant experience from one where they did not. They were able to do this just as well as mice that never had a brain injury. The cell transplants also prevented the mice from developing epilepsy, which affected more than half of the mice who were not treated with new interneurons.

Review Examines Advances and Limitations in Imaging Biomarkers of Post Traumatic Epilepsy

Traumatic brain injury (TBI) affects 2.5 million people annually within the United States alone, with over 300,000 severe injuries resulting in emergency room visits and hospital admissions. Severe TBI can result in long-term disability. Post traumatic epilepsy (PTE) is one of the most debilitating consequences of TBI, with an estimated incidence that ranges from 2% to 50% based on severity of injury. Conducting studies of PTE poses many challenges, because many subjects with TBI never develop epilepsy, and it can be more than 10 years after TBI before seizures begin. One of the unmet needs in the study of PTE is an accurate biomarker of epileptogenesis, or a panel of biomarkers, which could provide early insights into which TBI patients are most susceptible to PTE, providing an opportunity for prophylactic anticonvulsant therapy and enabling more efficient large-scale PTE studies. Several recent reviews have provided a comprehensive overview of this subject (Neurobiol Dis, 123, 2019, 3; Neurotherapeutics, 11, 2014, 231).

In this review, researchers describe acute and chronic imaging methods that detect biomarkers for PTE and potential mechanisms of epileptogenesis. They also describe shortcomings in current acquisition methods, analysis, and interpretation that limit ongoing investigations that may be mitigated with advancements in imaging techniques and analysis.

Dealing a Therapeutic Counterblow to Traumatic Brain Injury

A blow to the head or powerful shock wave on the battlefield can cause immediate, significant damage to a person’s skull and the tissue beneath it. But the trauma does not stop there. The impact sets off a chemical reaction in the brain that ravages neurons and the networks that supply them with nutrients and oxygen.

It is the secondary effects of traumatic brain injury (TBI), which can lead to long-term cognitive, psychological and motor system damage [as well as post-traumatic epilepsy], that piqued the interest of a team of NJIT biomedical engineers. To counter them, they are developing a therapy, to be injected at the site of the injury, which shows early indications it can protect neurons and stimulate the regrowth of blood vessels in the damaged tissue.

The challenge, researchers say, is that brain cells don’t regenerate as well as other tissues, such as bone, which may be an evolutionary strategy for preserving the synaptic connections that retain memories. To date, there is no effective treatment for restoring damaged neurons. The body’s protective mechanisms also make it difficult to penetrate the blood-brain barrier, which hampers the delivery of medications.

“Nerve cells respond to trauma by producing excessive amounts of glutamate, a neurotransmitter that under normal conditions facilitates learning and memory, but at toxic levels overexcites cells, causing them to break down. Traumatic brain injury can also result in the activation and recruitment of immune cells, which cause inflammation that can lead to short- and long-term neural deficits by damaging the structure around cells and creating a chronic inflammatory environment,” says Biplab Sarkar, a post-doctoral fellow in biomedical engineering and member of the team that presented this work at a recent American Chemical Society conference.

The team’s treatment consists of a lab-created mimic of ependymin, a protein shown to protect neurons after injury, attached to a delivery platform — a strand of short proteins called peptides, contained in a hydrogel — that was developed by Vivek Kumar, director of NJIT’s Biomaterial Drug Development, Discovery and Delivery Laboratory. After injection, the peptides in the hydrogel reassemble at the localized injury site into a nanofibrous scaffold that mimics extracellular matrix, the supporting structure for cells. These soft materials possess mechanical properties similar to brain tissue, which improves their biocompatibility. They promote rapid infiltration by a variety of stem cells which act as precursors for regeneration and may also provide a biomimetic niche to protect them.

Now in preclinical animal trials, rats injected with the hydrogel retained twice as many functioning neurons at the injury site as compared to the control group. They also formed new blood cells in the region.

“The idea is to intervene at the right time and place to minimize or reverse damage. We do this by generating new blood vessels in the area to restore oxygen exchange, which is reduced in patients with a TBI, and by creating an environment in which neurons that have been damaged in the injury are supported and can thrive,” Kumar says. “While the exact mechanism of action for these materials is currently under study, their efficacy is becoming apparent. Our results need to be expanded, however, into a better understanding of these mechanisms at the cellular level, as well as their long-term efficacy and the resulting behavioral improvements.”

Collaborators James Haorah, an associate professor of biomedical engineering, and his graduate student Xiaotang Ma at NJIT’s Center for Injury Biomechanics, Materials and Medicine have shown how a number of TBI-related chemical effects can disrupt and destroy integral brain vasculature in the blood-brain barrier, the brain’s protective border, promoting chronic inflammation that can lead to symptoms such as post-traumatic stress disorder and anxiety, among others. Their current work provides insights into the potential neuroprotective and regenerative response guided by the Kumar lab’s materials, while future studies will attempt to analyze other mediators of inflammation and blood flow in the brain.

Epilepsy Research Findings: August 2019

The past month has been filled with interesting research discoveries, including work done by CURE Grantee Dr. William Nobis and colleagues to advance our understanding of the areas of the brain that may be important in Sudden Unexpected Death in Epilepsy (SUDEP). In the field of epilepsy genetics, a large-scale study identified new epilepsy-associated genetic variants by examining the genetic make-up of more than 17,000 people with epilepsy. There is also intriguing research news looking at why cilantro, used in traditional medicine, may work to combat seizures.

Summaries of these research discoveries are below.

Plus, get epilepsy research news all month by downloading the new CURE mobile app! Find the details here.

Research Discoveries

  • SUDEP: A study featuring the work of CURE Grantee Dr. William Nobis and colleagues suggests that an area of the brain called the amygdala plays a role in dysfunctional breathing during seizures and possibly SUDEP. Learn More
  • Epilepsy Genetics: In one of the largest studies of its kind to examine the genetic make-up of individuals with epilepsy, scientists discover rare genetic variants associated with epilepsy. Learn More
  • Herbal Treatments: A study examines how the molecular action of cilantro, which is used as a traditional anticonvulsant medication, can help combat seizures. Learn More
  • Dementia and Epilepsy: Patients with dementia who are registered in the Swedish dementia registry were found to have increased rates of epilepsy. Learn More
  • Multiple Sclerosis and Epilepsy: Patients with multiple sclerosis have a higher risk of developing seizures compared with the general population. Learn More
  • SCN8A-Related Epilepsy: A study featuring the work of CURE Grantee Dr. Gemma Carvill and colleagues identified a set of neurons in the brains of mice that have a SCN8A gene mutation similar to humans that may be critical targets for therapeutic intervention. Learn More

Introducing the CURE Epilepsy Research Mobile App for research updates in the palm of your hand! Download today. iOS | Android

Epilepsy Research Findings: July 2019

This month’s edition of epilepsy news features recent research suggesting that inducing a seizure prior to surgery is just as effective for pinpointing the brain region where seizures originate as a spontaneous seizure as a spontaneous seizure. In addition, CURE Post-Traumatic Epilepsy initiative members Dr. Oleskii Shandra and Dr. Stefanie Robel published work indicating that the amount of a certain type of cell may increase in the brain following repeated, mild TBIs, causing epilepsy.

Safety updates on several anti-epileptic drugs were reported, including results showing pregabalin may be associated with increased suicidal behavior and other hazards, and that certain drugs used to treat epilepsy may increase the risk of dementia. Studies also highlight the need for improved counseling for safe and effective contraception for women with epilepsy, and the need for resources for people with epilepsy in low-income countries.

Summaries of all highlighted studies follow below. We have organized the findings into Research and Discoveries and Also Notable.

Research and Discoveries

Inducing Seizures to Stop Seizures
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Causing seizures by stimulating the brain may be a convenient and more cost-effective way to determine the brain region where seizures are originating prior to surgery.

New Research Could Help Predict Seizures Before They Happen
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A new study has found a pattern of molecules that appears in the blood before a seizure happens, which may lead to the development of an early warning system.

Pregabalin Associated with Increased Suicidal Behavior and Other Hazards 
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Gabapentinoids, a class of drugs used to treat epilepsy and other neurological disorders, are associated with an increased risk of suicidal behavior, unintentional overdoses, head/body injuries, and road traffic incidents and offences. Pregabalin was associated with higher hazards of these outcomes than gabapentin.

Study Furthers Understanding of the Development of Epilepsy Following Mild Traumatic Brain Injury (TBI)
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Featuring the work of CURE PTE Initiative members Dr. Oleskii Shandra and Dr. Stefanie Robel

A type of cell in the brain called an “atypical astrocyte” may increase following trauma, causing epilepsy following repeated, mild TBIs, according to a study by Drs. Oleskii Shandra and Stefanie Robel.

Even People with Well-Controlled Epilepsy May Be at Risk for Sudden Death
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Featuring the work of former CURE Grantee Elizabeth Donner

A new study shows the risk of Sudden Unexpected Death in Epilepsy (SUDEP) may apply to individuals whose epilepsy is well-controlled. Previous, smaller studies showed that SUDEP risk was highest among those with severe, difficult-to-treat epilepsy, however, this study suggests a sizeable minority of SUDEP occurred in patients thought to be treatment-responsive or to have benign epilepsies. The study found that SUDEP occurred in people who had not taken their last dose of epilepsy medication, those who were sleep deprived, and those who had not had a seizure in at least a year.

Anticholinergic Drugs May Increase Risk of Dementia 
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A study suggests that the possible link between anticholinergic drugs and an increased risk of dementia is strongest for certain classes of anticholinergic drugs, including antiepileptic drugs such as oxcarbazepine and carbamazepine.

Research into Cannabis Dosage Shows Reduced Seizures in Children with Severe Epilepsy
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Medicinal cannabis oil containing both cannabidiol (CBD) and a small amount of tetrahydrocannabinol (THC) can reduce or end seizures in children with severe, drug-resistant epilepsy, a study by the University of Saskatchewan has found.

Also Notable

The World Health Organization (WHO) Highlights the Scarcity of Treatment for Epilepsy in Low-Income Countries
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Three quarters of people living with epilepsy in low-income countries do not get the treatment they need, increasing their risk of dying prematurely and condemning many to a life of stigma, according to WHO.

Bringing Neuromodulation Therapies to Drug-Resistant Epilepsy Patients
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Researchers at the University of Alabama at Birmingham found that creating an epilepsy neuromodulation clinic improved access for patients and communication with referring physicians, achievement of expected outcomes for reducing or eliminating seizures, and the ability to train future providers in programming neuromodulation devices.

Encoded Therapeutics Gets $104M to Propel ‘Precision Gene Therapy’ for Dravet Syndrome
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Encoded Therapeutics received $104 million to fund a precision gene therapy for Dravet syndrome. The company will also use the funds to advance its preclinical programs and come up with new treatments for severe genetic disorders.

Improved Counseling Needed for Safe, Effective Contraception in Women With Epilepsy
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Over a third of women with epilepsy do not use highly effective contraception, despite the important, negative consequences of unintended pregnancy such as elevated risk of having offspring with congenital malformations. There is a need for more readily available information and counseling on safe and effective contraception for this community.

Study Furthers Understanding of the Development of Epilepsy Following Mild Traumatic Brain Injury (TBI)

Featuring the work of CURE PTE Initiative members Dr. Oleskii Shandra and Dr. Stefanie Robel

Focal traumatic brain injury (TBI) induces astrogliosis, a process essential to protecting uninjured brain areas from secondary damage. However, astrogliosis can cause loss of astrocyte homeostatic functions and possibly contributes to comorbidities such as posttraumatic epilepsy (PTE).

Scar-forming astrocytes seal focal injuries off from healthy brain tissue. It is these glial scars that are associated with epilepsy originating in the cerebral cortex and hippocampus. However, the vast majority of human TBIs also present with diffuse brain injury caused by acceleration-deceleration forces leading to tissue shearing. The resulting diffuse tissue damage may be intrinsically different from focal lesions that would trigger glial scar formation.

This study used mice of both sexes in a model of repetitive mild/concussive closed-head TBI, which only induced diffuse injury, to test the hypothesis that astrocytes respond uniquely to diffuse TBI and that diffuse TBI is sufficient to cause PTE. Astrocytes did not form scars and classic astrogliosis characterized by upregulation of glial fibrillary acidic protein was limited. Surprisingly, an unrelated population of atypical reactive astrocytes was characterized by the lack of glial fibrillary acidic protein expression, rapid and sustained downregulation of homeostatic proteins and impaired astrocyte coupling.

After a latency period, a subset of mice developed spontaneous recurrent seizures reminiscent of PTE in human TBI patients. Seizing mice had larger areas of atypical astrocytes compared with nonseizing mice, suggesting that these atypical astrocytes might contribute to epileptogenesis after diffuse TBI.

A Hit, a Hit-A Very Palpable Hit: Mild TBI and the Development of Epilepsy

In the United States, almost 3 million people sustain a traumatic brain injury (TBI) every year. The vast majority of these injuries are categorized as mild (?90%) and do not require hospitalization. Mild TBI is also frequently categorized as concussion, and it remains controversial as to whether, and to what extent mild TBI is a risk for the development of post-traumatic epilepsy.

It is well established, on the other hand, that severe TBI can lead to the development of a range of negative sequela in humans, including epilepsy. Moreover, the epileptogenic effects of severe TBI have been confirmed in rodents following controlled cortical impact and fluid percussion injury. In both rodent models [of PTE], a craniectomy is performed to expose the dura, and injury is induced either by a rigid impact device or hydraulically induced pressure. Both models can produce severe injuries, including neuronal loss, hemorrhage, extensive inflammatory changes, and mortality. These models have provided a wealth of data about potential epileptogenic mechanisms of severe TBI, but do not provide insight into the effects of mild TBI on epileptogenesis.

To address this gap in knowledge, Shandra and colleagues developed a closed-head model of post-traumatic epilepsy in mice following repetitive, mild TBI.

Epilepsy Research Findings: June 2019

This month’s round-up of epilepsy news features an announcement about a new antiepileptic rescue medication, NAYZILAM®. This therapy is the first FDA-approved nasal treatment option for people with epilepsy who experience episodes of frequent seizure activity.

We also highlight many research advances, from the discovery of a compound found in fruit and honey which can inhibit seizures to the development of a new drug to treat Dravet syndrome. Research in the cannabidiol (CBD) space has also advanced, with the creation of a synthetic form of CBD which may be easier to purify and does not need to be cultivated from hemp plants.

In more sobering news, reports over the past month show that one-third of epilepsy cases go without appropriate treatment for up to three years following diagnosis. In addition, people with psychogenic nonepileptic seizures (PNES) as well as epileptic seizures may be at a higher risk for sudden unexpected death in epilepsy (SUDEP)during the years immediately following diagnosis with PNES.

Summaries of all highlighted studies follow below. I’ve organized the findings into three categories: Treatment Advances, Research Discoveries, and Also Notable.

Treatment Advances

FDA Approves NAYZILAM® Nasal Spray to Treat Intermittent, Stereotypic Episodes of Frequent Seizure Activity in People Living with Epilepsy in the US
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The FDA has approved a New Drug Application for UCB’s newest antiepileptic drug NAYZILAM® (midazolam) nasal spray. This therapy is a benzodiazepine indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) distinct from a patient’s usual seizure pattern in individuals with epilepsy who are 12 years of age and older.

Study Advances More Effective Laser Ablation and Standard Epilepsy Surgery 
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In the largest study of its kind to date, researchers across 11 centers analyzed data on a relatively new minimally invasive alternative surgery for epilepsy. These researchers discovered changes that could make the procedure more effective in both laser ablation and standard surgery.

Research Discoveries

Brain Network Activity can Improve in Epilepsy Patients after Surgery
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Successful epilepsy surgery can improve brain connectivity similar to patterns seen in people without epilepsy, according to a new study published in the journal Neurosurgery. The study of 15 people with temporal lobe epilepsy is the first to show improvements in brain networks after surgery compared to a group of healthy subjects.

New Drug Could Help Treat Neonatal Seizures
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A new drug that inhibits neonatal seizures in rodent models could open new avenues for epilepsy treatment in human newborns. Researchers have found that gluconate—a small organic compound found in fruit and honey—acts as an anticonvulsant, inhibiting seizures by targeting the activity of channels that control the flow of chloride ions in and out of neonatal neurons.

Research Looks to Halt Stress-Induced Seizures Following Brain Injury
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The likelihood of developing epilepsy increases significantly with a traumatic brain injury. Stress and anxiety increase that likelihood even more dramatically. Researchers have been able to demonstrate that an injured brain responds differently to stress hormones than a healthy brain. The research team showed abnormal electrical activity in the brain tied to these stress-induced seizures and, most importantly, found a way to stop this activity from occurring.

Synthetic Version of Cannabidiol (CBD) Treats Seizures in Rats
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A synthetic, non-intoxicating analogue of CBD was found to be effective for treating seizures in rats. Researchers note the synthetic CBD alternative is easier to purify than a plant extract, eliminates the need to use agricultural land for hemp cultivation, and could avoid legal complications associated with cannabis-related products.

AZD7325 Has Seizure-Protective Effect in Mouse Model of Dravet Syndrome, Study Says
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Treatment with AZD7325, a compound that stimulates an inhibitory receptor in the brain, has a seizure-protective effect in a mouse model of Dravet syndrome. This treatment significantly increased the temperature threshold animals could withstand without experiencing any seizures during a hyperthermia-induced seizure test.

Children’s Brains Reorganize after Epilepsy Surgery to Retain Visual Perception
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Children can keep their full ability to process and understand visual information after brain surgery for severe epilepsy, according to a study funded by the National Eye Institute, part of the National Institutes of Health. This new report from a study of children who underwent epilepsy surgery and suggests that the lasting effects on visual perception can be minimal, even among children who lost tissue in the brain’s visual centers.

One-Third of Epilepsy Cases Go Untreated up to 3 Years After Diagnosis
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A small yet substantial subset of patients with newly diagnosed epilepsy go without appropriate treatment approximately 3 years after diagnosis. This gap in treatment may be increasing the risk for medical events and hospitalization in these patients.

Study Suggests ‘High Risk Period’ for SUDEP for People with Psychogenic Nonepileptic Seizures in Addition to Epileptic Seizures 
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Findings of a recently published study suggest that patients with comorbid epileptic seizures (ES) and Psychogenic Nonepileptic Seizures (PNES) can die from SUDEP and that there may be a high?risk period after the diagnosis of PNES is made. The authors state such patients should be closely monitored and provided with coordinated care of both their epilepsy and psychiatric disorder(s).

Also Notable

Fralin Biomedical Research Institute Neuroscientist Awarded Grant to Study Epilepsy
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Featuring CURE Grantee Dr. Sharon Swanger

Dr. Sharon Swanger of the Fralin Biomedical Research Institute was recently awarded a $1.7 million grant through the National Institute of Neurological Disorders and Stroke to study the role of glutamate receptors in the thalamus – an area of the brain involved in seizure generation. “If we can figure out how each [receptor] subtype functions and modulate select subtypes, then maybe we can target therapies to the circuit where the disease originated while leaving healthy circuits intact,” said Dr. Swanger.

Tool Helps GPs Predict Risk of Seizures in Pregnancy
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Doctors, midwives, and others can use a new risk calculator to identify those pregnant women at high-risk of seizures and to plan early referral for specialist input. The specialist could determine the need for close monitoring in pregnancy, labor, and after birth, and assess antiepileptic drug management, according to new research in PLOS Medicine. The study authors added that the model’s performance is unlikely to vary with the antiepilepsy drug dose management strategy – and that it could save maternal and infant lives.

Development of Epilepsy Prediction Device to Improve Independence for People with Epilepsy
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The University of Sydney’s Faculty of Engineering and Information Technologies is developing a system, NeuroSyd, which aims at real-time monitoring and processing of brain-signals while driving in a group of people living with epilepsy. NeuroSyd will be developed to deliver an early warning of the likelihood of an epileptic seizure.

Pfizer’s Lyrica at Doses 5mg and 10mg Fails Phase 3 Trial in Epilepsy
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Pfizer’s Lyrica has failed to meet its primary endpoint in a phase 3 trial in primary generalized tonic-clonic (PGTC) seizures. The study evaluated two doses of the drug – 5 mg and 10 mg – over a period of 12 weeks. Treatment with the drug did not result in a statistically significant reduction in seizure frequency versus placebo. Another phase 3 trial in May 2018 was successful, showing that a 14 mg dose of Lyrica resulted in a statistically significant reduction in seizure frequency versus placebo.

Research Looks to Halt Stress-Induced Seizures Following Brain Injury

For the over one million Canadians living with traumatic brain injury, the likelihood of developing epilepsy increases significantly because of their injury. When faced with stress or anxiety, that likelihood increases even more dramatically.

While a clinically well-known phenomenon, exactly what is occurring in the brain to cause this relationship has always been unclear.

Now, Western researchers have demonstrated a key factor in this relationship is that an injured brain responds differently to stress hormones. The team was able to show abnormal electrical activity in the brain tied to these stress-induced seizures and, most importantly, they found a way to stop it from occurring.

In a publication for eNeuro, “CRF Mediates Stress-Induced Pathophysiological High-Frequency Oscillations in Traumatic Brain Injury,” the research team used a rodent model of traumatic brain injury. When the animals were subjected to a stressful and anxiety provoking situation, all developed epileptic seizures. In controls with no injury, none developed seizure activity when a stressor was applied.

Epilepsy Research Findings: May 2019

In this month’s research news, treatments, genetic analysis, and preclinical work offer hope to those impacted by hard-to-treat or difficult-to-diagnose forms of epilepsy.

Exciting treatment developments include a positive Phase 3 clinical trial outcomefor the cannabidiol-based drug EPIDIOLEX® for the treatment of seizures associated with tuberous sclerosis complex. In addition, an improved treatment regimen targeting the severe, prolonged seizures that make up status epilepticus has been created.

In promising genetics news, a report from CURE’s own Epilepsy Genetics Initiativeunderscores the value of continued reanalysis of genetic information from people with epilepsy to increase their chances of obtaining a genetic diagnosis for their epilepsy.

Additionally, important preclinical work led by CURE Grantees Dr. Chris Dulla and Dr. Janice Naegele uncovers a potential drug to treat post-traumatic epilepsy and a way to restore the balance of brain activity and reduce seizures in temporal lobe epilepsy, respectively.

Summaries of all highlighted studies follow below. I’ve organized the findings into four categories: Treatment Advances, Diagnostic Advances, Research Discoveries, and Also Notable.

Treatment Advances

GW Pharmaceuticals Reports Reduction in Seizure Frequency for EPIDIOLEX® (cannabidiol) Oral Solution in Patients with Seizures Associated With Tuberous Sclerosis Complex
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GW Pharmaceuticals and Greenwich Biosciences announced positive top-line results of a Phase 3 clinical trial of EPIDIOLEX® (cannabidiol or CBD) in the treatment of seizures associated with Tuberous Sclerosis Complex (TSC). TSC is a rare and severe form of childhood-onset epilepsy. In this trial, EPIDIOLEX met its primary endpoint, which was a reduction in seizure frequency in the group given EPIDIOLEX compared to the placebo group.

Breakthrough for Children with Serious Epileptic Seizures
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A new treatment regimen of administering levetiracetam and phenytoin one after the other has given emergency medicine doctors a better way to treat severe, prolonged epileptic seizures in children. These treatment modifications will lower the chances of intubation and intensive care, as well as increase the chances of children recovering more quickly.

Diagnostic Advances

The Epilepsy Genetics Initiative: Systematic Reanalysis of Diagnostic Exomes Increases Yield
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Featuring CURE’s Epilepsy Genetics Initiative

Results from CURE’s Epilepsy Genetics Initiative (EGI) show that when the genetic information of a person with epilepsy is systematically reanalyzed, there is an increase in the return of a genetic diagnosis. Eight new diagnoses were made as a result of updated annotations or the discovery of novel epilepsy genes after the initial diagnostic analysis was performed. One novel epilepsy gene was discovered through dual interrogation of research and clinically generated whole-exome sequencing. According to this recently-published report, EGI’s contributions to gene discovery underscore the importance of data sharing and the value of collaborative enterprises.

Research Discoveries

Using a Drug that Mimics the Ketogenic Diet to Help Prevent Epilepsy after Traumatic Brain Injury
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Featuring the work of CURE Grantee Dr. Chris Dulla

Neuroscientists led by CURE Grantee Dr. Chris Dulla at Tufts University School of Medicine prevented the development of epileptic activity in mice after traumatic brain injury by using a drug that mimics the metabolic effects of the ketogenic diet.

Neural Stem Cell Transplantation May Reduce Abnormal Increases in New Cells in the Brains of Mice with Temporal Lobe Epilepsy
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Featuring the work of CURE Grantee Dr. Janice Naegele

According to a new, CURE-funded study featuring the work of grantee Dr. Janice Naegele, the transplantation of inhibitory cells into the brains of mice with temporal lobe epilepsy may reduce the abnormal growth of new neurons in an area of the brain called the hippocampus. This in turn could reduce brain hyperexcitability that leads to seizures.

Stimulating the Epileptic Brain Breaks Up Neural Networks to Prevent Seizures
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Responsive neurostimulation treats epilepsy by detecting seizures and intervening with a jolt of electric current. Over time, most patients find their seizures become fewer and further between. New evidence suggests responsive neurostimulation can remodel the brain to be less susceptible to seizures.

Scientists Discover Trigger Region for Absence Epileptic Seizures
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Scientists have discovered a neurological origin for absence seizures – a type of seizure characterized by very short periods of lost consciousness in which people appear to stare blankly at nothing. Using a mouse model of childhood epilepsy, a group of scientists has shown that absence epilepsy can be triggered by impaired communication between two brain regions: the cortex and the striatum.

Autism-Related Memory and Seizures Improved through Gene Repair in Adults
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Scientists have shown that correcting the protein deficiency caused by a genetic form of autism spectrum disorder in adult mice can improve behavioral and electrophysiological measures of both memory and seizure. The evidence suggests this is true even when the treatment is carried out well past what has traditionally been thought of as the critical window of early brain development.

Drug Used to Treat Multiple Sclerosis May Be Beneficial for Individuals with Epilepsy 
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A drug commonly used to treat multiple sclerosis may, after necessary modifications, one day be used to treat patients with epilepsy, according to research from the laboratory of Dr. Inna Slutsky.

Study Reveals How Glial Cells May Play Key Epilepsy Role
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A study provides potential new targets for treating epilepsy and novel fundamental insights into the relationship between neurons and their glial “helper” cells. This study reports finding a key sequence of molecular events in which the genetic mutation in a fruit fly model of epilepsy leaves neurons vulnerable to becoming hyper-activated by stress, leading to seizures.

Ketogenic Diet May Reduce Sudden Unexpected Deaths in Epilepsy, Mouse Study Suggests
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Sudden unexpected death in epilepsy (SUDEP) occurs more frequently during the early evening and is significantly prevented by prolonged use of the ketogenic diet, research in a mouse model of Dravet syndrome suggests. The reasons why this happens are unclear and should be examined in more depth by future studies, but these findings may be useful to understand why most SUDEP episodes happen at night and how certain diets can benefit people with epilepsy, especially those with Dravet syndrome, researchers say.

Attention, Behavioral Problems Common in New, Recent-Onset Juvenile Myoclonic Epilepsy
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Children with new recent-onset juvenile myoclonic epilepsy are more likely to have difficulty with executive, attention, and verbal faculties than their healthy peers and are also more likely to use a greater number of academic services, researchers found.

Also Notable

Zogenix Receives Refusal to File Letter from FDA for FINTEPLA® New Drug Application
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Zogenix announced that it received a Refusal to File letter from the FDA regarding its New Drug Application (NDA) for FINTEPLA® for the treatment of seizures associated with Dravet syndrome. Upon its preliminary review, the FDA determined that the NDA was not sufficiently complete to permit a substantive review.