CURE Discovery: Predicting Acquired Epilepsy Following a Brain Infection

A potential method of predicting who will get epilepsy following a brain infection, such as that brought on by malaria, has been discovered. This breakthrough is the result of work by two CURE grantees, Dr. Bruce Gluckman and Dr. Steven Schiff of Pennsylvania State University.

Individuals who contract cerebral malaria (malaria accompanied by a coma, typically spread by mosquitos) are at a substantially increased risk of developing epilepsy.1 Malaria is especially widespread in non-industrialized areas of the world and often affects children.2 Because malaria is so widespread, it may be the most significant cause of post-infection epilepsy in the world today. Currently, there are no methods to predict who will develop epilepsy, or any means of preventing epilepsy after such an infection.

This makes Dr. Gluckman and Dr. Schiff’s discovery so critical. Together with their team members Fatemeh Bahari and Dr. Paddy Sstentongo, they found a combination of brain and heart activity in mice that could accurately predict which animals would develop seizures and epilepsy after infection with malaria.3

Using their CURE grant, Drs. Gluckman and Schiff studied the connection between cerebral malaria and epilepsy by first developing a mouse “model” replicating malaria-induced epilepsy. In addition, they investigated possible ways to determine which mice would go on to develop epilepsy after infection.

Using the mice which developed epilepsy after infection with malaria, the research team measured two important variables often associated with epilepsy: the activity of the brain and heart. They found abnormal brain activity immediately followed by abnormal heart activity – but only in the animals which went on to develop epilepsy.

This discovery represents a possible biomarker for predicting epilepsy following infection with malaria. In other words, these may be measurable indicators to determine the infected individuals who will develop epilepsy. Furthermore, the abnormal brain and heart activity was detectable as early as 14 weeks before the first seizure, opening a potential window during which therapeutic interventions might be used to prevent epilepsy.

Drs. Gluckman and Schiff plan to continue this work, using these findings to develop treatment methods for people who contract cerebral malaria to prevent them from developing epilepsy. They are hopeful their discovery will lead to a means to eliminate not only post-malarial epilepsy, but also epilepsy caused by other types of brain injuries.

1 Ngoungou and Preux. Cerebral malaria and epilepsy. Epilepsia 2008; 49(s6):19-24.
2 World Health Organization. World malaria report 2017. http://www.who.int/malaria/publications/world-malaria-report-2017/report/en/.
3 Bahari et al. A brain-heart biomarker for epileptogenesis. J Neurosci 2018; pii: 1130-18.

CURE Discovery: New Ultraflexible Electrodes for Minimally Invasive Electrical Recordings

A less invasive yet more accurate, safe, and effective method of recording seizures from deep layers of the brain may now be possible, thanks to the work of CURE grantee Dr. Flavia Vitale.1

Dr. Vitale, of the University of Pennsylvania, and a team of researchers engineered a method of delivering thin, ultraflexible electrodes deep into neural tissue. The way these electrodes are constructed and inserted limits the brain damage associated with the penetrating electrodes currently used for recording neural signals. This new and improved technology may allow researchers and clinicians to better pinpoint changes in electrical activity in the brains of people with epilepsy.

Recording this electrical activity is essential to understanding the epileptic “map” of a person’s brain. Understanding the map helps doctors locate where seizures originate (the focus) and learn how they spread. With this information, doctors can more effectively treat epilepsy. Knowing the focus of an individual’s epilepsy can, for example, help guide epilepsy surgery or the implantation of an anti-seizure device. This kind of precision isn’t always possible with current clinical mapping tools because of their invasiveness and low-resolution, Dr. Vitale notes.

The thinner, softer, and higher-resolution electrodes can be focused, moved, and adjusted after implantation, reaching deep layers of the brain while causing minimal damage. Thus far, the team has successfully tested this system in the small, fresh-water organism called hydra as well as in rats.

Dr. Vitale is now performing new experiments to demonstrate that this updated electrode technology is safer and less damaging than the placement of stiffer, commercial electrodes.

As a next step in her CURE project, Dr. Vitale will also focus on understanding the safety of her electrode system after it has been implanted for a long period of time. By completing the development of this novel recording system, her overall goal is to increase the understanding of brain activity patterns in individuals with epilepsy, improving the safety and accuracy of recordings and the treatment of epilepsy.

1 Vitale F, et al. Fluidic microactuation of flexible electrodes for neural recording. Nano Lett 2018; 18(1):326-335.

CURE Discovery: Improving Sleep

CURE Discovery: Improving Sleep with Small Environmental Changes May Decrease Seizures

Relatively small changes in environmental factors which improve the ‘internal clock’ (otherwise known as the circadian rhythm) and the quality of sleep lead to decreases in seizures in mice with similarities to Dravet syndrome, a severe form of epilepsy. These promising results are the latest findings from the lab of CURE grantee Dr. Franck Kalume of Seattle Children’s Hospital, whose grant is generously supported through the BAND Foundation.

Individuals with Dravet syndrome have problems with their circadian rhythm and with regulating their sleep.1 Upon observing that mice with similarities to Dravet syndrome have similar sleep disturbances,2 Dr. Kalume and his team set out to determine if improving circadian rhythm and sleep patterns in these mice could reduce the occurrence of seizures.

To improve circadian rhythm in the mice, the team confined either meals or exercise to nighttime, when mice are typically active. The team limited these activities during the day, when mice typically sleep. As a result of these simple changes, the team found that the mice became more active at night and less active during the day, an indication of improved circadian rhythm. The mice also showed improvements in the quality of their sleep.

Significantly, restricting these activities to nighttime led to a decrease in the incidence of irregular brain activity that is characteristic of an epileptic brain, an indication that improvements in sleep practices may improve epilepsy.

Dr. Kalume and his team next plan to confine both exercise and meals to nighttime to see if this leads to an even greater reduction of seizures. They also plan to determine the effect of these changes on the risk of sudden death in these mice, as these mice and humans with Dravet syndrome are more susceptible to Sudden Unexpected Death in Epilepsy (SUDEP).

These important results contribute to our understanding of the relationship between sleep and epilepsy and provide hope for the development of new therapies to improve epilepsy outcomes. Dr. Kalume and his team hope these studies will lead to practical steps not involving medication that individuals with epilepsy can take to improve their circadian rhythm and sleep to reduce seizures and the risk of SUDEP.

1 Licheni SH et al. Sleep problems in Dravet syndrome: a modifiable comorbidity. Dev Med Child Neurol 2018; 60(2):192-198.
2 Kalume F et al. Sleep impairment and reduced interneuron excitability in a mouse model of Dravet Syndrome. Neurobiol Dis. 2015; 77: 141-54.

CURE Discovery: Spider Venom Peptide May Reduce Seizures

A new treatment for Dravet syndrome, a rare and catastrophic form of drug-resistant epilepsy, may soon be on the horizon thanks to the work of CURE grantees Dr. Glenn King of the University of Queensland and Dr. Steven Petrou of the Florey Institute of Neuroscience and Mental Health. Drs. King and Petrou identified a peptide found in spider venom which can reduce seizures and mortality in mice modeling the symptoms of human Dravet syndrome.1

The majority of Dravet syndrome cases are caused by mutations in a gene that lead to too little inhibition and too much excitation in the brain, triggering the hyperexcitability seen with seizures.2,3 Drs. King and Petrou found that the spider venom peptide works to restore the balance of inhibition and excitation in the brains of Dravet syndrome mice, decreasing hyperexcitability and reducing seizures. Furthermore, the team found that this peptide also decreases mortality in these mice.

Drs. King and Petrou next plan to investigate this peptide’s effects on other symptoms associated with Dravet syndrome, such as anxiety, autistic traits, and sleep disturbance. They will also explore ways to develop this peptide into a treatment for epilepsy, including methods of delivering the peptide into the brain.

Besides providing a potential new treatment for Dravet syndrome, these results are especially important because they highlight the therapeutic power of venomous substances, Dr. King notes. These substances work due to their ability to target the brain and alter its activity. Dr. King is optimistic that venomous substances may also be used in the treatment of types of epilepsy other than Dravet syndrome, as well as other brain disorders.

We at CURE are also hopeful this line of research will open new treatment possibilities for rare and difficult-to-treat epilepsies. As noted by Dr. King, the overall goal of this research is to develop therapeutics that will reverse all symptoms of Dravet syndrome and enable those with the disorder to live normal lives.

1 Richards et al. Selective Nav1.1 activation rescues Dravet syndrome mice from seizures and premature death. PNAS 2018; 115(34):E8077-E8085.
2 Bender et al. SCN1A mutations in Dravet syndrome: Impact of interneuron dysfunction on neural networks and cognitive outcome. Epilepsy Behav 2012; 23(3):177-186.
3 Liautard et al. Hippocampal hyperexcitability and specific epileptiform activity in a mouse model of Dravet syndrome. Epilepsia 2013; 54(7):1251-1261.

Sudden Death Among Children with Epilepsy: 4x More Likely than Previously Thought

1.11 out of 1,000 children with epilepsy die suddenly each year, according to a Canadian study by CURE grantee Dr. Elizabeth Donner of the University of Toronto. (1) Dr. Donner’s estimates confirm 2017 results garnered from the Swedish National Death Registry that also found the annual rate of sudden death to be 1.11 per 1,000 children with epilepsy. (2)

Both of these recent studies are in contrast to previous estimates which showed that Sudden Death in Epilepsy (aka SUDEP) affects 1 in 4,500 children with epilepsy each year. (3)

Dr. Donner has spent much of her career identifying and studying cases of SUDEP to determine how often sudden death occurs in children with epilepsy and who is at risk. A recipient of CURE’s 2009 Sudden Unexpected Death in Epilepsy Award, Dr. Donner set out to create a Canadian pediatric SUDEP registry in collaboration with the Canadian Paediatric Surveillance Program, with the goal of obtaining data on every child with a sudden death and epilepsy.

Dr. Donner hopes that this increased understanding of how many children are affected by SUDEP will lead to the identification of risk factors. She aims to save lives by understanding which children with epilepsy are most at-risk, so that therapies can be developed to prevent sudden death.

Although there is currently no known ‘cure’ for SUDEP, the efforts of Dr. Donner and her team have increased understanding about this devastating consequence of epilepsy. Through the work of dedicated researchers like Dr. Donner, we may soon be able to not only identify those that are at risk for SUDEP but also offer ways to prevent SUDEP from occurring at all.

1 – Keller AE et al. Incidence of sudden unexpected death in epilepsy in children is similar to adults. Neurology 2018; 91(2):e107-e111.
2 – Sveinsson O et al. The incidence of SUDEP: A nationwide population-based cohort study. Neurology 2017; 89(2): 170-177.
3 – Harden C et al. Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2017; 88(17):1674-1680.

CURE Discovery: Transplanting Inhibitory Neurons Can Reduce Seizures

CURE Grantee Dr. Janice Naegele of Wesleyan University has been working on harnessing the brain’s own inhibitory power as a treatment to reduce excitability and “quiet” the overly excitable epileptic brain. As a promising first step, she and her team have successfully shown that transplantation of mouse inhibitory neurons into the mouse hippocampus – a brain structure that is often involved in epilepsy – can reduce the number of seizures in mice with temporal lobe epilepsy. (1)

Temporal lobe epilepsy is the most common form of epilepsy, with neuronal loss being one of its hallmark traits. (2,3) The loss of inhibitory neurons can be an important factor in the development or worsening of the disorder, (4) because the balance between excitatory and inhibitory neuronal activity is essential for proper brain function. Fewer inhibitory neurons can decrease inhibitory neurotransmission, in turn leading to excessive neuronal excitation, seizures, and epilepsy. One focus of Dr. Naegele’s epilepsy research has been to find a way to increase inhibition in the hyperexcitable epileptic brain. (5)

Dr. Naegele used her CURE grant to focus on transplanting both mouse and human inhibitory neurons into the hippocampus of mice with temporal lobe epilepsy. She hypothesized that these inhibitory neurons would wire up with existing neurons, increasing inhibitory transmission and decreasing the hyperexcitability that characterizes temporal lobe epilepsy. This type of treatment is called “regenerative medicine” because it uses healthy tissue to restore normal brain functioning. An advantage of regenerative medicine is that the transplanted cells can potentially replace lost or damaged inhibitory neurons and also integrate into the existing brain circuitry. This treatment would provide a cure for seizures by addressing the root cause, unlike standard antiepileptic drugs that simply treat the symptoms of seizures.

Indeed, as shown by advanced imaging techniques, the inhibitory neurons Dr. Naegele’s team transplanted into the brains of mice with temporal lobe epilepsy formed new, functional connections with excitatory neurons already present in the hippocampus, providing the increased inhibition that likely led to fewer seizures in these mice. (1)

Following the success of quieting seizures using the implantation of mouse inhibitory neurons, Dr. Naegele and her team are now focused on a means to quiet seizures by implanting human inhibitory neurons, pushing this research one step closer to being a viable treatment for people with epilepsy. As part of their strategy, they are keeping in mind important potential differences in neuronal generation and transmission between humans and mice. (6)

Dr. Naegele’s research brings an exciting possibility to the future of epilepsy treatment: the transplantation of a type of neuron that already exists in the human brain with the goal of stopping seizures. While work still remains, CURE applauds the progress Dr. Naegele has made thus far. We share Dr. Naegele’s hopes that her approach becomes a non-drug method of treating those affected by not only temporal lobe epilepsy, but other forms of epilepsy as well.

1 Henderson et al. Long-term seizure suppression and optogenetic analysis of synaptic connectivity in epileptic mice with hippocampal grafts of GABAergic interneurons. J Neurosci 2014; 34(40):13492-13504.
2 Pitkänen A, Sutula TP. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Neurol 2002; 1(3):173-181.
3 Engel J Jr, Williamson PD, Weiser HG. Mesial temporal lobe epilepsy. In: Epilepsy: a comprehensive textbook (Engel J Jr, Pedley TA, eds) 1997: 2417-2426.
4 Kumar SS, Buckmaster PS. Hyperexcitability, interneurons, and loss of GABAergic synapses in entorhinal cortex in a model of temporal lobe epilepsy. J Neurosci 2006; 26(17):4613-4623.
5 Van Zandt MA, Naegele JR. GABAergic synapse dysfunction and repair in temporal lobe epilepsy. (2017) Synaptic Plasticity Thomas Heinbockel, IntechOpen; DOI: 10.5772/67218. Available from: https://www.intechopen.com/books/synaptic-plasticity/gabaergic-synapse-d….
6 Naegele JR. Controversial brain study has scientists rethinking neuron research. (2018) Available from: https://theconversation.com/controversial-brain-study-has-scientists-ret…

CURE Discovery: New Cause of Severe Childhood Epilepsy Found – Genetic Mutation in the CUX2 Gene

CURE Grantee Dr. Gemma Carvill has identified a new cause of epilepsy: a mutation in the gene CUX2. Dr. Carvill’s discovery was recently published in the Annals of Neurology.1

The discovery provides an important advance in our understanding of the causes of a class of severe childhood epilepsies. This class includes childhood epileptic encephalopathy, an aggressive and severe group of treatment-resistant epilepsy disorders in which children can have profound cognitive and neurological deficits.2,3

Dr. Carvill began her research into the ways specific genetic mutations lead to childhood epileptic encephalopathy in 2015 as the result of a 1-year CURE Taking Flight Award. This award program encourages young investigators to conduct independent research which could lead to a cure for epilepsy. When Dr. Carvill recieved the CURE Taking Flight Award, she was a Postdoctoral Fellow at the University of Washington.

Dr. Carvill studied the ways genetic mutations lead to epilepsy. Her initial findings suggested that mutations in a class of genes important in determining the structure of DNA could impact several genes involved in epilepsy, making this class of genes a potential target of future epilepsy therapy development.

Since receiving her CURE award, Dr. Carvill’s career has certainly “taken flight” – she is now Assistant Professor of Neurology and Pharmacology at Northwestern University. Still, Dr. Carvill has remained committed to her quest to understand the genetic mechanisms behind severe childhood epilepsy. In her latest study, Dr. Carvill partnered with Dr. Gaetan Lesca of the Lyon University Hospital, located in France, to identify de novo mutations in the gene CUX2 as a new cause of epilepsy. De novo mutations are changes present only in the affected patient and not in their healthy parents. CUX2 is important in binding DNA and promoting the expression of certain target genes. Mutations in CUX2 cause errors in this process that can lead to epilepsy.

Dr. Carvill’s report details her international study of 9 patients aged 6 months to 21 years who first began having seizures early in life. To identify the mutation in the CUX2 gene, Dr. Carvill and her team used, among other techniques, a test called whole exome sequencing. This test analyzes a person’s genes to identify changes in their DNA. All 9 patients had the same CUX2 mutation. The team found that the majority of these patients had severe treatment-resistant epilepsy that started early in life, severe intellectual disability, and did not have speech appropriate for their age.

Besides finding an important genetic cause of severe childhood epilepsy, which can now be targeted for the development of therapeutic interventions, Dr. Carvill’s collaboration with Dr. Lesca highlights the importance of international efforts to identify new genes important in epilepsy. As Dr. Carvill notes, these genetic mutations are very rare and therefore collaborative efforts with multiple patient populations make it more likely that a rare genetic mutation can be identified and studied.

In the future, Dr. Carvill plans to further explore the genetic mechanisms behind these devastating childhood epilepsies. Her goal, which we at CURE share, is that treatments and cures can be found for all of the amazing children affected by epilepsy and their wonderful families, too.

Citations

1 Chatron N et al. The epilepsy phenotypic spectrum associated with recurrent CUX2 variant. Ann Neurol2018; 6 [Epub ahead of print]
2 Cross H and Guerrini R. The epileptic encephalopathies. Handb Clin Neurol 2013; 111:619-626.
3 Jehi L, Wylie E, Devinsky O. Epileptic encephalopathies: Optimizing seizure control and developmental outcome. Epilepsia 2015; 56(10):1486-1489.

CURE Discovery: Potential Target Area in the Brain for Prevention of Epilepsy-Related Sudden Death

An area of the brain known as the amygdala may be critical in the conscious control of breathing, making it an important target area for research into epilepsy-related sudden death, according to a study recently published by CURE Grantee Dr. William Nobis of Northwestern University Feinberg School of Medicine.1 As part of a team led by Dr. Christina Zelano, also of Northwestern University, Dr. Nobis found that stimulation of the amygdala consistently induced apnea, or disrupted breathing, in a group of individuals with temporal lobe epilepsy. This finding is significant because it points to a possible role of the amygdala in what may be the most severe epilepsy-related complication, Sudden Unexpected Death in Epilepsy (SUDEP).

SUDEP occurs when a seemingly healthy person with epilepsy dies for no obvious reason,2 most often at night or during sleep. While research suggests that several factors including respiratory and cardiac dysfunction contribute to SUDEP,3,4 the precise biological processes remain unknown. By implanting electrodes into the brains of seven patients undergoing surgical evaluation for temporal lobe epilepsy, Dr. Nobis and his team were able to pinpoint specific regions of the amygdala that are important in controlling respiration, identifying areas possibly important in the cessation of respiration that characterizes SUDEP. Furthermore, the team found that by instructing patients to inhale during an apnea-inducing stimulation of the amygdala, they were able to prevent apnea providing an area upon which to focus development of therapeutic strategies to prevent SUDEP.

With funding from CURE, Dr. Nobis is now pushing this research to uncover the mechanisms behind SUDEP even further. He and his team think that the amygdala may be activated during seizures, causing it to lead to cessation of respiration and SUDEP. By using a genetic animal model of epilepsy that has a high rate of SUDEP, the team hopes to identify and examine the specific neurons within the amygdala that project to important respiratory centers in other parts of the brain, allowing the amygdala to influence respiratory function – and the loss of respiratory function that occurs in SUDEP.

Early results from Dr. Nobis’s current CURE project have begun to identify populations of neurons in the amygdala that project to areas of the brain important in respiration. The team next plans on examining how these neurons are activated in response to seizures, and how changes in the excitability of these neurons might correspond with changes in respiratory function that could lead to SUDEP.

In the future, Dr. Nobis hopes to be able to determine whether it is possible to target this subset of neurons within the amygdala to prevent SUDEP from occurring, providing a large step forward for SUDEP research and possible therapies for SUDEP prevention. Thanks to CURE-funded researchers like Dr. Nobis, we are moving closer to being able to eliminate the sudden and devastating death of individuals with epilepsy.

1 Nobis WP et al. Amygdala-stimulation-induced apnea is attention and nasal-breathing dependent. Ann Neurol 2018; 83(3):460-471.
2 Nashef. Sudden unexpected death in epilepsy: terminology and definitions. Epilepsia 1997; 38(11 Suppl):S6-8.
3 Surges et al. Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms. Nat Rev Neurol 2009; 5(9):492-504.
4 Bagnall et al. Genetic basis of sudden unexpected death in epilepsy. Front Neurol 2017; 8:348.

CURE Discovery: Genetic Research Finds Potential Alternatives to Brain Surgery for Children with Cortical Dysplasia

A Potential Alternative is Already in Clinical Trial

Recent research by CURE grantee Dr. Jeong Ho Lee of the Korea Advanced Institute of Science and Technology has shed important light on the genetic mutations that lead to focal cortical dysplasia, a severe form of pediatric epilepsy that inadequately responds to available treatment options. Genetic mutations were found in the brain tissue of individuals affected by a particular subtype of focal cortical dysplasia (focal cortical dysplasia type II) that is characterized by brain abnormalities, leading to seizures and epilepsy.

Conventional genetic testing methods to identify genetic mutations in those with epilepsy often use blood or saliva from patients. However, these latest results from Dr. Lee and his team suggest that certain epilepsy-related gene mutations may only be detectable when brain tissue is analyzed.

Brain-Only Mutations in Genes that Cause Focal Cortical Dysplasia

By comparing blood and saliva samples to samples of brain tissue from a group of 40 individuals who had previously undergone brain surgery for focal cortical dysplasia type II, Dr. Lee and his team found that a significant number of these individuals (12.5%) had brain-only mutations in genes TSC1 and TSC2. Together with the previous pioneering work of his team to identify brain-only mutations in the MTOR gene in individuals with focal cortical dysplasia type II, they revealed that brain-only mutations in genes within the mTOR brain signaling pathway (including the genes TSC1, TSC2 and MTOR) are found in up to 30% of individuals with focal cortical dysplasia. The fact that these mutations were found only in the brain means that these mutations would be undetectable by conventional genetic testing methods, suggesting that investigation of brain-only mutations should be explored to a greater extent.

In addition to identifying brain-only mutations leading to focal cortical dysplasia, Dr. Lee and his team also addressed the current lack of adequate animal models to better study the disorder. The team was able to successfully recreate the brain-only mutations in genes TSC1 and TSC2 in developing mice, providing a much-needed animal model for further examination of the ways in which gene mutations can lead to focal cortical dysplasia type II.

Clinical Trials for the Treatment of Focal Cortical Dysplasia

Furthermore, the team provided evidence that mTOR inhibitors, such as rapamycin or everolimus, are promising anti-epileptic drugs for the treatment of focal cortical dysplasia. In fact, everolimus is currently under phase II clinical trial for the treatment of focal cortical dysplasia.

As noted by Dr. Lee, because focal cortical dysplasia is a drug-resistant epilepsy, many children with the disorder require invasive brain surgery as treatment. However, even in cases where surgery is performed, up to 40% of these children may still have seizures. By identifying genes associated with focal cortical dysplasia as well as creating a new way of studying the genetic mechanisms behind the disorder, Dr. Lee and his team have made progress towards the creation of novel, non-surgical targets at which to aim treatments for this devastating form of drug-resistant childhood epilepsy.

[1] Lim et al. Somatic mutations in TSC1 and TSC2 cause focal cortical dysplasia. Am J Human Genet 2017; 100(3):454-472.
[2] Guerrini et al. Diagnostic methods and treatment options for focal cortical dysplasia. Epilepsia 2015; 56(11):1669-86.
[3] Gaitanis and Donahue. Focal cortical dysplasia. Ped Neurol 2013; 49:79-87.
[4] Poduri et al. Genetic testing in the epilepsies – developments and dilemmas. Nat Rev Neurol 2014; 10(5):293-299.
[5] Lim et al. Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy. Nat Med 2015; 21(4):395-400.

CURE Discovery: Preventing Post-Traumatic Epilepsy with 2-Deoxy-D-Glucose Treatment

The latest results from a CURE-funded grant represent a promising advance in the quest to prevent post-traumatic epilepsy. Dr. Thomas Sutula from the University of Wisconsin and his team have found that the administration of 2-Deoxy-D-Glucose (2DG) following a traumatic brain injury can significantly reduce the subsequent development of post-traumatic epilepsy in a rodent model.

The finding that 2DG can prevent the development of post-traumatic epilepsy in rats is exciting for several reasons. 2DG is a sugar-like molecule that has been proposed to mimic the ketogenic diet – a diet that is highly effective in the treatment of difficult-to-treat epilepsies. Therefore, like the ketogenic diet, 2DG may also have therapeutic effects for individuals that have already developed epilepsy (in this case, post-traumatic epilepsy). 2DG is also already being used in the treatment of other illnesses, including cancer, and can likely progress rapidly to a clinical trial for post-traumatic epilepsy. Furthermore, with this research, Dr. Sutula and his team have successfully utilized a novel rat model that more readily develops a post traumatic-epilepsy-like syndrome with frequent seizures following traumatic brain injury, providing a great research tool in the quest for treatments and a cure for post-traumatic epilepsy.

Post-traumatic epilepsy is a type of epilepsy that develops following a traumatic brain injury such as a bump or blow to the head. Post-traumatic epilepsy accounts for nearly 20% of all symptomatic epilepsies in the general population, and is one of the most common causes of acquired epilepsy. Post-traumatic epilepsy can be particularly devastating because no known prevention or cure for the disorder currently exists.

Because post-traumatic epilepsy can develop months or even years after an initial traumatic brain injury, there is a critical window of time during which the development of post-traumatic epilepsy might be prevented, if only a preventative measure were in existence. For these reasons, Dr. Sutula’s finding that 2DG significantly reduces the development of post-traumatic epilepsy in his novel breed of rat within this critical window is an important one.

In the future, Dr. Sutula and his team plan on taking strategic steps to push their research forward towards an Investigational New Drug trial to test the effectiveness of this drug in the prevention of post-traumatic epilepsy in humans. In this way, Dr. Sutula hopes that his research will impact the lives of individuals suffering from post-traumatic epilepsy, or those with the potential to develop post-traumatic epilepsy, as soon as possible.