Drug Resistant Epilepsy

Partnering with scale-up Wazoku, Angelini Pharma announced yesterday (March 11) that it aims to make use of the collective wisdom and expertise of its 700,000-strong crowd to drive innovation in epilepsy treatment. The challenge, titled ‘New Digital Approaches to Target Discovery in Epilepsy,’ marks the beginning of a strategic collaboration between Angelini Pharma and Wazoku. The initiative seeks to uncover new digital approaches to target identification in epilepsy, with a specific emphasis on collecting and integrating multiple data types and developing new algorithms and tools for target selection. Epilepsy, a neurological disorder affecting over 50 million individuals worldwide, presents a significant challenge, and according to the research undertaken by the company, approximately one-third of patients experience drug-resistant seizures. Urgent need for more epilepsy treatments Recognizing the urgent need for more effective therapies, Angelini Pharma aims to tackle innovative digital solutions to enhance target identification in drug-resistant epilepsy, thereby bolstering its early-stage pipeline and supporting its commitment to brain health. Rafal Kaminski, chief scientific officer at Angelini Pharma, said he was optimistic about the potential impact of the open innovation challenge. He said: “Through this open innovation challenge, we expect to identify innovative digital solutions with the potential to improve the identification of new targets in drug-resistant epilepsy that can be validated preclinically. This would help us build our early-stage pipeline, thus supporting our efforts in brain health.” googletag.cmd.push(function () { googletag.display('text-ad1'); }); Open innovation - a powerful tool The company, known for its dedication to researching, developing, and commercializing health solutions, particularly in the field of brain health, views this collaboration with Wazoku as a significant step in driving innovation in epilepsy treatment. This marks the company's first Open Innovation Challenge with Wazoku, signaling its commitment to embracing innovative approaches to address unmet medical needs. Open innovation has emerged as a powerful tool in the pharmaceutical sector, facilitating accelerated drug discovery and development while addressing challenges such as rising operational costs and talent shortages. Benefits of collective intelligence Dino Ribic, innovation consultant at Wazoku, highlighted the transformative potential of open innovation, saying: “Progressive companies like Angelini Pharma have recognized the benefits of collective intelligence, and I can't wait to see what the Wazoku Crowd delivers in this instance.” The Wazoku Crowd, comprising a diverse network of expert problem solvers, boasts a success rate of over 80% in solving more than 2,500 challenges, delivering over 200,000 innovations in the process. With cash prizes totaling up to $25,000 available for the "New Digital Approaches to Target Discovery in Epilepsy" challenge, Angelini Pharma anticipates receiving groundbreaking proposals from the Wazoku Crowd. The challenge is set to close on Monday next week, (18 March 2024).

These wide-ranging waves quickly link the specific constellations of brain regions that work in harmony to perform a task. In the space of just a few seconds, a person walking down a city block might check their phone, yawn, worry about making rent, and adjust their path to avoid a puddle. The smell from a food cart could suddenly conjure a memory from childhood, or they could notice a rat eating a slice of pizza and store the image as a new memory. For most people, shifting through behaviors quickly and seamlessly is a mundane part of everyday life. For neuroscientists, it's one of the brain's most remarkable capabilities. That's because different activities require the brain to use different combinations of its many regions and billions of neurons. How it manages to do this so rapidly has been an open question for decades. The Study In a paper published March 8 in Nature Human Behaviour, a team of researchers, led by Joshua Jacobs, associate professor of biomedical engineering at Columbia Engineering, shed new light on this question. By carefully monitoring neural activity of people who were recalling memories or forming new ones, the researchers managed to detect how a newly appreciated type of brainwave -- traveling waves -- influences the storage and retrieval of memories. "Broadly, we found that waves tended to move from the back of the brain to the front while patients were putting something into their memory," said the paper's co-author Uma R. Mohan, a postdoctoral researcher at NIH and former postdoctoral researcher in the Electrophysiology, Memory, and Navigation Laboratory at Columbia Engineering. "When patients were later searching to recall the same information, those waves moved in the opposite direction, from the front towards the back of the brain," she said. In the brains of some of the study's 93 participants, waves traveled in other directions. "There was a lot of diversity across patients, so we implemented a framework based on the direction an individual's oscillations 'preferred' to travel," Mohan said. The researchers say these findings advance fundamental neuroscience research and point toward diagnostic and therapeutic approaches for memory-related disorders. "We think the work may lead to new approaches for interfacing with the brain. By measuring the direction that a person's brain waves move, we may be able to predict their behavior," Jacobs said. The Challenge Brain waves are patterns of electrical oscillations that reflect the state of hundreds or thousands of individual neurons at a particular moment. One major question, which remains unsettled, is whether brain waves drive activity or simply occur as a byproduct of neural activity that was already happening. Researchers who study brain waves have tended to treat them as a stationary phenomenon that occurs in a particular region, noting when oscillations in multiple regions seem synchronized. In this study, Mohan and her colleagues contribute to a growing understanding of these oscillations differently, as "traveling waves" that spread across the brain's cortex, the outermost layer that supports higher cognitive processing. Mohan compares the traveling waves to the ripples that would spread outward after a pebble was thrown into a pond. "We're looking at neural oscillations not as independent stationary things but as things that are constantly and spontaneously moving across the brain in a dynamic way," Mohan said. This relatively new way of understanding brain waves is an exciting step in neuroscience because it offers a pathway to explaining how the brain quickly coordinates activity and shares information across multiple regions. The Experiments and Results This study drew on data from participants who were being treated for drug-resistant epilepsy at hospitals across the United States. The experiments occurred while the participants had grids or strips of electrodes temporarily implanted on the surface of the brain, beneath the skull, to determine where the patients' seizures arise. For the researchers, these electrodes offer the chance to perform experiments that wouldn't otherwise be feasible. "It's a rare opportunity to be able to see what's going on directly from the brain while the participants are engaged in different cognitive behaviors," Mohan said. During the experiments, researchers recorded the participants' brain activity while they performed tasks that required memorizing and recalling lists of words or letters. After the experiments, the researchers analyzed the brain activity from each participant in the context of what they were doing in the memory task and how well they performed. "I implemented a method to label waves traveling in one direction as basically 'good for putting something into memory.' Then we could see how the direction switched over the course of the task," Mohan said. This method builds on previous research from the Jacobs lab by expanding the mathematical framework used to make sense of the vast quantities of data these experiments produced. "The waves tended to go in the participant's encoding direction when that participant was putting something into memory and in the opposite direction right before they recalled the word," she said. " Overall, this new work links traveling waves to behavior by demonstrating that traveling waves propagate in different directions across the cortex for separate memory processes." The data also showed that participants tended to perform the memory task more accurately when the traveling waves were moving in the appropriate direction for memory storage and recall. "These findings shed light on the mechanisms that underlie memory processing. More broadly, they help us better understand how the brain supports a wide range of behaviors that involve precisely coordinated interactions between brain regions," Mohan said. Potential Impact and Future Directions As traveling waves are increasingly well understood, they could be the basis for a new class of diagnostic tools that recognize abnormal patterns in brain activity. There is also significant therapeutic potential. "If someone's waves are moving in the wrong direction when they're about to try to remember something, that might put them in a poor memory state," Mohan explained. "If you could apply stimulation in the right way, you could maybe push those waves to move in a different direction, bringing about a fundamentally different memory state." Advances in understanding traveling waves offer significant potential for human-computer interaction. In terms of both research and application, Mohan notes that memory is just the starting point. "I am interested in how characteristics of cortical traveling waves change to support a wide range of cognitive functions, including attention and associative memory," she said. "The direction of traveling wave propagation may tell us where information is moving across the brain at each moment, showing us how different parts of the brain transfer information during behavior," Jacobs said.

NRTX-1001 is being evaluated in an ongoing Phase I/II clinical trial in adults with drug-resistant focal epilepsySAN FRANCISCO, March 07, 2024 (GLOBE NEWSWIRE) -- Neurona Therapeutics, a clinical-stage biotherapeutics company advancing regenerative cell therapy candidates for the treatment of neurological disorders, today announced that updated data from its ongoing Phase I/II clinical trial of NRTX-1001, an investigational allogeneic cell therapy candidate that is being developed for treatment of drug-resistant mesial temporal lobe epilepsy (MTLE), will be presented at the American Academy of Neurology (AAN) 2024 Annual Meeting, which will be held April 13-18, 2024, in Denver, CO. AAN 2024 Presentation Details:Title: First-in-Human Trial of NRTX-1001 GABAergic Interneuron Cell Therapy for Treatment of Focal Epilepsy - Emerging Clinical Trial ResultsFormat: Oral (abstract # 5721, presentation #002)Session: S19: Epilepsy Clinical Trials and Long-term StudiesPresenter: John Hixson, M.D., Senior Medical Director, Neurona TherapeuticsDate: Monday, April 15, 2024Time: 3:42 p.m. MT About NRTX-1001NRTX-1001 is a regenerative neural cell therapy candidate derived from human pluripotent stem cells. The fully-differentiated neural cells, called interneurons, secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Delivered as a one-time dose, the human interneurons are intended to integrate on-target and durably silence seizure activity in the epileptic region of the brain. NRTX-1001 is manufactured in Neurona’s in-house GMP facility using proprietary methods. About Mesial Temporal Lobe Epilepsy (MTLE)According to the Centers for Disease Control and Prevention, an estimated 3.4 million Americans have epilepsy, and 25-35% live with ongoing seizures despite treatment with approved drugs, illustrating a substantial unmet medical need in this community. MTLE is a common type of focal epilepsy in adults and primarily affects the internal structures of the temporal lobe, where seizures often begin in a structure called the hippocampus. For people with seizures resistant to anti-seizure drugs, epilepsy surgery - where the damaged temporal lobe is surgically removed or ablated by laser - can be an option. However, the current surgical options are not available or effective for all subjects, are tissue-destructive, and can have significant adverse effects. About Neurona’s Clinical Trial of NRTX-1001 for MTLEThe ongoing clinical study is designed to evaluate the safety and efficacy of a single administration of NRTX-1001 for drug-resistant MTLE. The first stage of the trial is an open-label dose-escalation study in up to 10 people with drug-resistant MTLE, with five subjects in the first cohort treated at a starting dose and five subjects in the second cohort to be treated at a higher dose. Subjects treated with a single infusion of NRTX-1001 cells will be monitored for safety and effects on their epilepsy disease symptoms. Subject recruitment is underway at epilepsy centers across the United States. For more information, please visit www.clinicaltrials.gov (NCT05135091). The first part of the clinical trial is supported by an $8.0 million grant from the California Institute for Regenerative Medicine (CIRM; CLIN2-13355). With $5.5 billion in funding and more than 150 active stem cell programs in its portfolio, CIRM is one of the world’s largest institutions dedicated to helping people by bringing the future of cellular medicine closer to reality. About Neurona TherapeuticsNeurona is focused on developing regenerative cell therapy candidates with single-dose curative potential. Neurona’s investigational allogeneic, off-the-shelf, cell therapy candidates are designed to provide long-term repair of dysfunctional neural networks for multiple neurological disorders. For more information about Neurona, visit www.neuronatherapeutics.com. Forward-Looking StatementsThis press release includes forward-looking statements that are subject to risks and uncertainties, including risks and uncertainties inherent in the clinical development of therapeutic candidates, risks that early clinical data collected from a small number of subjects may not be predictive of data when NRTX-1001 is tested in larger clinical trials, the possibility that timelines may change, and difficulties associated with obtaining sufficient data to demonstrate safety and efficacy to support regulatory approval. NRTX-1001 is an investigational candidate and is being evaluated in ongoing clinical trials. NRTX-1001 has not been approved by any regulatory authority for commercial use or deemed to be safe or effective for any indication. Investor Contacts: Sylvia WheelerWheelhouse LSAswheeler@wheelhouselsa.comElizabeth Wolffe, Ph.D.Wheelhouse LSAlwolffe@wheelhouselsa.comMedia Contact: Aljanae ReynoldsWheelhouse LSAareynolds@wheelhouselsa.com