Treatments

Fintepla Safely Reduces Seizures in Children Younger than 2, Study Finds

Article published by Dravet Syndrome News

Treatment with Fintepla (fenfluramine) appeared to be reasonably safe and lower seizure frequency in five children with Dravet syndrome who started on the therapy before they were two years old, scientists in Italy reported. These findings are noteworthy because in the US and European Union, Fintepla is approved for Dravet patients ages two and older. “We demonstrated that [Fintepla] used in patients younger than two years may offer excellent tolerability and a clinically significant reduction in seizure frequency,” the researchers wrote. The researchers highlighted that two of the children showed slight improvements in some measures of cognitive development after starting on Fintepla, in contrast to Dravet’s typical progression where cognitive development slows. Though the scientists stressed that it’s too early to make definitive conclusions, they said their study offers hope that reducing seizures in early life may help to protect cognitive development over time.

The Mozart Effect Myth: Listening to Music Does Not Help Against Epilepsy

Article published by Neuro Science News

Over the past 50 years, there have been remarkable claims about the effects of Wolfgang Amadeus Mozart’s music. Reports about alleged symptom-alleviating effects of listening to Mozart’s Sonata KV448 in people with epilepsy attracted a lot of public attention. However, the empirical validity of the underlying scientific evidence has remained unclear. Now, a new comprehensive research synthesis by Sandra Oberleiter and Jakob Pietschnig from the University of Vienna, based on all available scientific literature on this topic, showed that there is no reliable evidence for such a beneficial effect of Mozart’s music on epilepsy. The origin of these ideas can be traced back to the long-disproven observation of a temporary increase in spatial reasoning test performance among students after listening to the first movement allegro con spirito of Mozart’s sonata KV448 in D major. “Mozart’s music is beautiful, but unfortunately, we cannot expect relief from epilepsy symptoms from it”, conclude the researchers.

How Yoga May Help Reduce Epilepsy Seizures, Anxiety

Article published by Medical News Today

A new study in Neurology reports that doing yoga may help reduce seizure frequency, anxiety, and feelings of stigma that frequently comes with having epilepsy. “People with epilepsy often face stigma that can cause them to feel different than others due to their own health condition and that can have a significant impact on their quality of life,” said Dr. Manjari Tripathi, a study author and neurologist with the All India Institute of Medical Sciences in New Delhi. “This stigma can affect a person’s life in many ways including treatment, emergency department visits, and poor mental health. Our study showed that doing yoga can alleviate the burden of epilepsy and improve the overall quality of life by reducing this perceived stigma.” Researchers looked at people with epilepsy with an average age of 30 in India. They measured stigma based on participants’ answers to questions about being discriminated against, feeling different from other people, and whether they feel they contribute to society. The scientists then identified 160 people meeting the criteria for experiencing stigma. Participants averaged one seizure per week and, on average, took at least two antiseizure medications. The team then randomly selected subjects to receive yoga therapy or sham yoga therapy. Researchers reported that people doing yoga were more likely to have reduced perception of stigma. The team also discovered people who did yoga were more than four times as likely to have more than a 50% reduction in their seizure frequency after six months than the people who did sham yoga. There was also a significant decrease in anxiety symptoms for those who did yoga compared to people who did not. Researchers said they saw improvements in quality of life measures and mindfulness.

Neurona Therapeutics Announces Publication in Cell Stem Cell Reporting the Development of Investigational Novel Regenerative Cell Therapy Strategy for Drug-resistant Focal Epilepsy

Article published by Global Newswire

Neurona Therapeutics recently published data on the development and characterization of human stem cell-derived, medial ganglionic eminence inhibitory interneurons for the potential treatment of focal epilepsy. In a preclinical study, administration of a single dose of the cells in a chronic model of drug-resistant mesial temporal lobe epilepsy (MTLE) resulted in long-lasting and consistent suppression of focal seizures, as well as improvements in neuropathology and an increase in survival. The study also demonstrated a potentially broad, safe, and effective dosing range in the model. The data support the development of Neurona Therapeutics’ regenerative cell therapy candidate, NRTX-1001, which is being evaluated in an ongoing Phase I/II clinical trial of a one-time dose in people with drug-resistant MTLE (NCT05135091).

Epilepsy Research News: September 2023

This issue of Epilepsy Research News includes summaries of articles on:

The Cerebellum as a Source of Generalized Convulsive Seizures

A recent study provides new insights into how convulsive seizures happen, implicating a “circuit” in the brain, specifically a connection of neurons between the cerebellum and thalamus, in driving convulsive seizures. To investigate the importance of this circuit in causing seizures, the team utilized a technique called optogenetic imaging to record the activity of neurons in the brain before, during, and after convulsive seizures. The team found that a group of neurons in a specific area of the thalamus called the ventral posteromedial nucleus were initiating convulsive seizures. The team then found that neurons in the cerebellum that connect to this area of the thalamus not only significantly contribute to the seizures, but that blocking activity from the cerebellum to the thalamus blocked seizures from occurring. The team noted that the findings not only deepen the understanding of how seizures originate but also create the possibility of targeting this cerebellum-thalamus circuit to treat convulsive seizures.

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Examining the Benefit of Rapid Genome Sequencing for Infantile Epilepsy

A recent study shows that rapid genome sequencing (a process that looks for changes across the entire genome) can provide a rapid diagnosis of genetic mutations and influence clinical care of infants with new-onset epilepsy. As part of this study, researchers sequenced the genomes of 100 infants with unexplained seizures along with their parents to better understand the potential diagnostic value of this approach for infantile epilepsy. The researchers found that across all children enrolled in the study, 43% received a diagnosis within weeks, and that diagnosis impacted the medical outcomes in nearly 90% of those cases, guiding treatment options for over half. This study provides an initial framework for further investigation of the long-term benefits of early genetic diagnosis in infants, and the potential use of targeted “precision” treatments that are specific to an infant’s genetic diagnosis.

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Large Genetic Study Provides Insights on Why Epilepsy Develops and Potential Treatments

The largest genetic study of its kind has discovered specific changes in our DNA that increase the risk of developing epilepsy. The research advances our knowledge of why epilepsy develops and may inform the development of new treatments for the condition. The researchers identified 26 distinct areas in our DNA that appear to be involved in epilepsy. This included 19 which are specific to a particular form of epilepsy called genetic generalized epilepsy. They were also able to identify 29 genes within these DNA regions that probably contribute to epilepsy. The researchers also showed that many of the current medications for epilepsy work by targeting the same epilepsy risk genes that were highlighted in the study. Furthermore, based on their data, the researchers were able to propose some potentially effective alternative drugs. The researchers noted that these discoveries, only achieved through international collaboration, help us to better understand the genetics of this type of epilepsy and potential treatments.

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Preventive Epilepsy Treatment with Vigabatrin Does Not Improve Neurocognitive Development in Infants with Tuberous Sclerosis Complex (TSC)

In new study results, researchers found that administering the preventive epilepsy treatment vigabatrin (Sabril ®) prior to seizure onset did not improve neurocognitive outcomes in TSC infants at two years of age. In the original results, this study (known as the PREVeNT trial) showed that preventative treatment delayed the start and lowered the number of infantile spasms in infants with TSC. This study enrolled 84 infants with TSC between 2016 and 2020, who had been diagnosed with TSC either through prenatal testing, physical examination, or genetic testing, but had yet to have any seizures. Infants who developed a specific EEG biomarker that indicates a risk of developing seizures were then placed in two groups, one receiving preventative vigabatrin treatment and one receiving a placebo. In this new study, the researchers found that infants who received vigabatrin still had drug-resistant epilepsy at 24 months, that focal seizures remained prominent in the infants, and there was no benefit in cognitive outcomes. The researchers state that these findings indicate the need to develop more effective therapies to treat cognitive and behavioral dysfunction in TSC.

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Advances in Cannabidiol (CBD) for Epilepsy Treatment and Prevention

A series of recently published articles details new breakthroughs in the field of medical cannabinoids for epilepsy and seizure disorders. Two publications review the effectiveness of CBD, a compound found in cannabis, in treating epilepsy and seizures. Another publication in the series describes the results of a meta-analysis (a type of study that reviews and combines the results of multiple other studies) to determine the overall effectiveness and safety of CBD treatment in children with genetic epilepsies such as Dravet syndrome, Lennox-Gastaut syndrome, and Tuberous Sclerosis Complex. This analysis revealed that CBD was effective in managing these genetic epilepsies, albeit with an increase in adverse events such as diarrhea, somnolence, sedation, and potential drug interactions. A separate publication showed potential effects of CBD as a prevention against seizures that are similar to those associated with temporal lobe epilepsy. Together, these publications provide information on the use of CBD in the treatment of epilepsy and open up the possibility of utilizing CBD in individuals at risk for developing epilepsy.

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RNA Therapeutics for Epilepsy: An Emerging Modality for Drug Discovery

Abstract found on PubMed

Drug discovery in epilepsy began with the finding of potassium bromide by Sir Charles Locock in 1857. The following century witnessed the introduction of phenotypic screening tests for discovering antiseizure medications (ASMs). Despite the high success rate of developing ASMs, they have so far failed in eliminating drug-resistance and in delivering disease-modifying treatments. This emphasises the need for new drug discovery strategies in epilepsy. RNA-based drugs have recently shown promise as a new modality with the potential of providing disease-modification and counteracting drug-resistance in epilepsy. RNA therapeutics can either be directed toward non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), or towards messenger RNAs (mRNAs). The former show promise in sporadic, non-genetic epilepsies as interference with ncRNAs allow for modulation of entire disease pathways, while the latter seems more promising in monogenic childhood epilepsies. Here, we describe therapeutic strategies for modulating disease-associated RNA molecules and highlight the potential of RNA therapeutics for the treatment of different patient populations such as sporadic, drug-resistant epilepsy, and childhood monogenic epilepsies.

Biohaven Announces Positive Data from EEG Biomarker Study of Epilepsy Treatment

Article published by Healio News

A global clinical-stage biopharmaceutical company announced positive biomarker data from its exploratory phase 1 electroencephalogram biomarker study of novel and selective Kv7.2/Kv7.3 activator BHV-700 to treat epilepsy.

According to a release from Biohaven, the study was designed to evaluate qualitative changes from baseline in EEG spectral power following single 10 mg, 25 mg or 50 mg doses of BHV-7000 in healthy volunteers.

EEG spectral power is a measure derived from quantitative analysis of EEG signals that examine rhythmic activity at different frequencies, including delta [1-3.5 Hz], theta [3.5-7.5 Hz], alpha [7.5-13 Hz], beta [13-30 Hz] and gamma [30-100 Hz], per the release.

According to data cited in the release, at the lowest dose of 10 mg given to 12 participants, those with BHV-7000 concentrations at or greater than EC50 showed mean increases in EEG spectral power in beta and gamma bands that were not observed in the group of subjects with drug concentrations less than EC50.

Further, in 11 participants given the highest dose of 50 mg, increases in EEG spectral power were observed across all bands and distributed over all cortical brain regions.

The study additionally revealed BHV-7000 was well-tolerated, and its safety profile was consistent with prior safety data from the phase 1 SAD/MAD trial completed to date, which recorded a “markedly” lower incidence of somnolence, speech disorder and memory impairment.

Cognitive Effect of Antiseizure Medications in Medial Temporal Lobe Epilepsy

Abstract found on PubMed

Background and purpose: The specific effects of antiseizure medications (ASMs) on cognition are a rich field of study, with many ongoing questions. The aim of this study was to evaluate these effects in a homogeneous group of patients with epilepsy to guide clinicians to choose the most appropriate medications.

Methods: We retrospectively identified 287 refractory patients with medial temporal lobe epilepsy associated with hippocampal sclerosis. Scores measuring general cognition (global, verbal and performance IQ), working memory, episodic memory, executive functions, and language abilities were correlated with ASM type, number, dosage and generation (old vs. new). We also assessed non-modifiable factors affecting cognition, such as demographics and epilepsy-related factors.

Results: Key parameters were total number of ASMs and specific medications, especially topiramate (TPM) and sodium valproate (VPA). Four cognitive profiles of the ASMs were identified: (i) drugs with an overall detrimental effect on cognition (TPM, VPA); (ii) drugs with negative effects on specific areas: verbal memory and language skills (carbamazepine), and language functions (zonisamide); (iii) drugs affecting a single function in a specific and limited area: visual denomination (oxcarbazepine, lacosamide); and (iv) drugs without documented cognitive side effects. Non-modifiable factors such as age at testing, age at seizure onset, and history of febrile seizures also influenced cognition and were notably influenced by total number of ASMs.

Conclusion: We conclude that ASMs significantly impact cognition. Key parameters were total number of ASMs and specific medications, especially TPM and VPA. These results should lead to a reduction in the number of drugs received and the avoidance of medications with unfavorable cognitive profiles.

Biological Rhythms and Epilepsy Treatment

Abstract found on PubMed

Approximately one-third of patients with epilepsy are drug-refractory, necessitating novel treatment approaches. Chronopharmacology, which adjusts pharmacological treatment to physiological variations in seizure susceptibility and drug responsiveness, offers a promising strategy to enhance efficacy and tolerance. This narrative review provides an overview of the biological foundations for rhythms in seizure activity, clinical implications of seizure patterns through case reports, and the potential of chronopharmacological strategies to improve treatment. Biological rhythms, including circadian and infradian rhythms, play an important role in epilepsy. Understanding seizure patterns may help individualize treatment decisions and optimize therapeutic outcomes. Altering drug concentrations based on seizure risk periods, adjusting administration times, and exploring hormone therapy are potential strategies. Large-scale randomized controlled trials are needed to evaluate the efficacy and safety of differential and intermittent treatment approaches. By tailoring treatment to individual seizure patterns and pharmacological properties, chronopharmacology offers a personalized approach to improve outcomes in patients with epilepsy.

A Review on Epilepsy, Current Treatments, and Potential of Medicinal Plants as an Alternative Treatment

Abstract found on PubMed

Epilepsy is considered common neurological diseases that threaten the lives of millions of people all around the world. Since ancient times, different forms of medications have been used to treat this condition. Adverse events associated with treatments and the residence time of available drugs caused to search for safer and more efficient therapies and drugs remain one of the major areas of research interest for scientists. As one of the therapeutics with fewer side effects, plants and their essential oils can be considered replacements for existing treatments. Medicinal plants have proven to be an effective natural source of antiepileptic drugs; most of them have their mechanism of action by affecting GABA receptors in different paths. Cannabis indica and Cymbopogon winterianus are well-known plant species with antiepileptic activities. The current review presenting a list of plants with antiepileptic effects aims to pave the way for finding alternative drugs with fewer side effects for scientists.