Disruptive, Impulse Control, and Conduct Disorders

Ingelheim, Germany, Oxford and Belfast, UK, April 29, 2025 – Boehringer Ingelheim, the University of Oxford, and Cumulus Neuroscience are joining forces to provide insights into the day-to-day experiences of people living with psychiatric disorders, and how these experiences relate to their brain activity. The first-of-its-kind study will use novel technology to quantify brain activity, mood, and behavior at home in people who have been diagnosed with borderline personality disorder (BPD), an often neglected group of patients. The aims are to explore the acceptability of this technology in patients and gain quantitative, fine-grained, insights that could potentially guide the research and development of much-needed new therapies. Current clinical and lab-based assessments rely on retrospective recall of symptoms. They are thus limited by how accurately patients remember past events and only provide a snapshot in time of an individual’s clinical state. Moreover, self-reported questionnaires lack objectivity. This can lead to an incomplete or inaccurate picture of the overall experience of the individual and the failure of new medicines in clinical studies. This new study aims to change that. It will use Cumulus´ NeuLogiq® neuroassessment platform for the first time in people diagnosed with borderline personality disorder. This platform enables the tracking of brain function over time, both in the clinic, and from the comfort of a study participant’s home. Participants use a tablet to perform gamified versions of established objective behavioral tasks, while wearing the NeuLogiq headset which records EEG (electroencephalogram) brain waves that are precisely time-synced to the tasks. The intent is to capture data that will provide a more accurate picture of brain network activity.  In 2019, one in eight people worldwide were estimated to be living with a mental health condition, and half of the adult population can expect to experience a mental illness by age 75.i,ii*  People diagnosed with severe mental health conditions experience reduced life expectancy relative to the general population, with around 14 years of potential life lost,1 and the economic consequences of mental health conditions can be enormous.iii That’s why Boehringer Ingelheim is embracing ‘Precision Psychiatry’. This in-depth research approach delves into the neurobiology of symptoms with the goal of uncovering more targeted and holistic treatment solutions that address specific symptoms in people living serious mental illness to help them to live fulfilling lives. Kate Saunders, Associate Professor in the Department of Psychiatry of the University of Oxford says, “People diagnosed with borderline personality disorder experience a range of symptoms, including changeable mood, impulsivity, and associated difficulties in interpersonal relationships, all of which can have a significant impact on their lives. We're looking forward to exploring this new technology in people living with BPD, in collaboration with the scientists at Cumulus and Boehringer Ingelheim, to gain new insights into the mechanisms which underpin the symptoms people given this diagnosis experience.  This could open up pathways for the development of new therapies.” Dr. Hugh Marston, Senior Vice President and Global Head Neuroscience & Mental Health, Boehringer Ingelheim says, “Boehringer Ingelheim is committed to developing novel therapeutics to address the major unmet needs of people living with mental health disorders. If this platform is successfully validated in this patient population, it could be a game-changer for studies investigating novel precision psychiatry treatments. It could help us identify biomarkers for stratification and provide a rich dataset for reverse-translation.” “Many psychiatric conditions disrupt cognitive function, meaning that patients may find it harder to manage their daily life or continue to work effectively,” said Brian Murphy, PhD, Co-founder and Chief Scientific Officer of Cumulus. “These underappreciated symptoms can change from day to day, so frequent real-world measurement is important if we want to find new therapies that improve activities of daily living and quality of life. Today, we are fortunate that wearable technologies and AI are enabling a new era of drug development where we can understand objectively how a drug affects cognitive function and the underlying brain mechanisms that drive it.”  The study will be conducted by the Department of Psychiatry of the University of Oxford at the Warneford Hospital. It will frequently collect EEG and behavioral assessments, alongside remote measures of mood and activity. The main aims are to assess the feasibility of using the Cumulus platform in young adults aged 18-35 and to provide a rich dataset about brain activity and behavior in BPD for in-depth analysis.  Thirty participants who have been diagnosed with BPD and 20 participants with no diagnosed mental health disorder will be recruited. Dr. Lauren Atkinson, from the Department of Psychiatry who will be senior researcher on the study says, “We are looking forward to working with people diagnosed with borderline personality disorder and prioritising research important to them. One of the key features of a BPD diagnosis is affective dysregulation. By regularly capturing mood, alongside measures of brain activity and cognitive function over an extended period of time, we hope to better capture patient experience and use objective measures to understand more about what is happening at those key moments.” *The mental health conditions studied in this epidemiological research included: panic disorder and/or agoraphobia, generalized anxiety disorder, post-traumatic stress disorder, social phobia, specific phobia, major depressive disorder, bipolar disorder, alcohol abuse disorder, alcohol dependence disorder, drug abuse disorder, drug dependence disorder, attention deficit/hyperactivity disorder, and intermittent explosive disorder.About Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. Our approximately 54,500 employees serve over 130 markets to build a healthier and more sustainable tomorrow. Learn more at www.boehringer-ingelheim.com (global) or www.boehringer-ingelheim.com/uk (UK). About Cumulus Neuroscience Our mission is to generate the data and insights required to accelerate the diagnosis and management of central nervous system (CNS) disorders for millions of patients and caregivers around the world. At Cumulus Neuroscience we are advancing NeuLogiq®, an AI-based, multi-domain digital biomarker platform designed with 10 of the world's leading pharma companies. This novel platform provides the critical data and insights needed for faster, more robust and cost-effective decision-making in clinical trials and patient care. NeuLogiq enables study sponsors to capture large amounts of real-world clinical data repeatedly over time, across multiple behavioral and physiological domains, in the clinic and at home. Together with machine learning (ML) analytics, Cumulus simplifies and improves the robustness of CNS clinical trials, providing objective assessment of study inclusion and treatment outcomes. About Oxford University The University Department of Psychiatry’s mission is to conduct world-class research, teach psychiatry to medical students, develop future researchers in a graduate programme, teach doctors in training, promote excellence in clinical practice, and develop and provide innovative clinical services. It supports research in four key areas: neurobiology, psychological treatments, developmental psychiatry and social psychiatry. The Department is committed to the translation of scientific discovery into benefits for patients. www.psych.ox.ac.uk  Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the ninth year running, and ​number 3 in the QS World Rankings 2024. At the heart of this success are the twin-pillars of our ground-breaking research and innovation and our distinctive educational offer. Oxford is world-famous for research and teaching excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research alongside our personalised approach to teaching sparks imaginative and inventive insights and solutions. Through its research commercialisation arm, Oxford University Innovation, Oxford is the highest university patent filer in the UK and is ranked first in the UK for university spinouts, having created more than 300 new companies since 1988. Over a third of these companies have been created in the past five years. The university is a catalyst for prosperity in Oxfordshire and the United Kingdom, contributing £15.7 billion to the UK economy in 2018/19, and supports more than 28,000 full time jobs. Media Contacts  Boehringer Ingelheim: Dr. Reinhard Malin Boehringer Ingelheim Corporate Center GmbH  Innovation Unit/Bio Comms, Corp. Affairs  Media + PR  press@boehringer-ingelheim.com  Cumulus:Tina Sampath tina.sampath@cumulusneuro.com Oxford University: Lisa Jones Communications Manager Department of Psychiatry, University of Oxford, Warneford Hospital lisa.jones@psych.ox.ac.uk 

After coming up short in a phase 3 trial for the second time, Otsuka has discontinued development of AVP-786. The drug was under investigation as a therapy for agitation that can accompany Alzheimer's disease. Otsuka Pharmaceutical is packing up an Alzheimer’s disease med after a phase 3 study failed to move the needle on measures of agitation associated with dementia.   The results were originally issued in February, with Otsuka reporting that AVP-786 did not achieve the primary endpoint that measured a change in baseline on a rating scale of agitation compared with placebo. The therapy had been under development through Otsuka’s U.S. subsidiaries for agitation associated with dementia due to Alzheimer's. At the time, Otsuka did not have full details of the study to present. In announcing the termination of AVP-786 today, the Japanese pharma is still keeping those details under wraps. AVP-786 has traveled a bumpy path through the clinic, including failing a different phase 3 trial in 2019. That disappointment for the NMDA receptor antagonist came just months after Otsuka posted positive results for AVP-786 in a separate phase 3 trial. Otsuka acquired AVP-786 from CNS specialist Avanir Pharmaceuticals in a 2015 buyout worth $3.5 billion. Also coming in that deal was Nuedexta, a treatment approved in 2010 for pseudobulbar affect (PBA), a rare disorder that causes outbursts of laughing or crying that accompany some neurological conditions. Nuedexta uses the same chemical compound—dextromethorphan hydrobromide and quinidine sulfate—as AVP-786. Otsuka also investigated AVP-786 in early-stage trials for intermittent explosive disorder, schizophrenia and traumatic brain injury.

Pictured: Collage of a brain and stem cells/Taylor Tieden for BioSpace Could stem cell therapies make the Parkinsonian brain generate dopamine again? Some companies, including BlueRock Therapeutics and International Stem Cell Corporation, are banking on it. Parkinson’s disease is currently treated with dopamine replacement agents, but the efficacy of these drugs is limited and they come with challenging side effects. Some in the stem cell field say these new therapies, though early-stage, could ultimately be a better, safer option. In a March 2024 report, GlobalData touted the “early promise” of cell therapies to address the motor and non-motor symptoms of Parkinson’s disease with minimal adverse effects. ‘Resetting the Clock’ With more than 10 million people around the world living with Parkinson’s disease, the treatment market is currently valued at $5.56 billion and is expected to reach $6.63 billion by 2029. A progressive disease of the nervous system, Parkinson’s is characterized by the degradation of neurons in the part of the brain that controls movement. The loss of these neurons slows the production of dopamine, leading to a combination of motor symptoms, including writhing movements, resting tremors and muscle stiffness, which can be lessened with levodopa and dopamine-agonists—drugs that behave like dopamine. The disease also brings non-motor symptoms, including depression, hyposmia, dysphasia and psychosis. Levodopa is currently the “gold standard” treatment for Parkinson’s. Although it provides a dopamine kick, the drug is laden with severe adverse effects, including hallucinations, dyskinesia and loss of impulse control. These side effects can occur a dopamine response is stimulated in several parts of the brain through medication, Agnete Kirkeby, a stem cell scientist at Lund University and the University of Copenhagen, told BioSpace. Levodopa also provides only a small window of relief for patients, Kirkeby said. In an emailed statement to BioSpace, GlobalData analysts Lorraine Palmer and Christie Wong said early clinical trials of stem cell transplantation in Parkinson’s have shown a reduction in motor and non-motor symptoms. “However, the subject size of these clinical trials have been small and were not powered to measure statistical significance,” they said, adding that large-scale, pivotal trials will be required to investigate how safely and how well the therapies work. “Currently, there are no therapies which recover lost dopaminergic neurons so if cell therapies do end up meeting their hopes of replacing dopaminergic neurons,” they could be market changers, Palmer and Wong said. During her postdoctoral days at Lund, Kirkeby, along with her supervisor, designed a method to grow transplantable dopamine cells from embryonic stem cells. “When we transplant the cells, we transplant [them] to a very particular region of the brain that is involved in motor control,” she explained. Kirkeby is currently leading a preclinical study of STEM-PD sponsored by Lund, a stem-cell therapy intended to replace lost dopamine neurons in the brains of Parkinson’s patients. Cambridge, Mass.–based BlueRock Therapeutics, a Bayer subsidiary, is also developing a stem cell–based therapy, called bemdaneprocel. “You can think about it almost like you’re resetting the clock for those people who live with Parkinson’s disease by providing them cells, which have the potential to integrate and re-establish some of the neural networks and circuitry in that part of the brain,” Ahmed Enayetallah, head of development at BlueRock, told BioSpace. Cell Therapies for Parkinson’s in the Pipeline There are currently seven stem cell therapies for Parkinson’s disease in Phase I clinical trials or later. Three of these—sponsored by BlueRock, Celavie Biosciences and International Stem Cell Corporation—have completed and published results. In the Phase I trial of bemdaneprocel, neuronal progenitor stem cells derived from donors were transplanted into 12 patients, whose progress was monitored for 18 months. During the first year, the patients were treated with immunosuppressive drugs. The cells survived and bemdaneprocel was tolerated by patients throughout the trial period, Enayetallah said, even after immunosuppression was discontinued. The trial met multiple clinical endpoints and broadened the window at which the patients experienced relief from disease symptoms, he added. Unlike with current treatments, Enayetallah said, there were no reported cases of dyskinesia or other adverse events except gastrointestinal bleeding and seizure, which he attributed to the surgical procedure and not the therapy itself. Having a one-time treatment for Parkinson’s disease would be a paradigm shift, Enayetallah said. Another therapy, ISC-hpNSC, is in development by California-based International Stem Cell Corporation. Upon completion of a Phase I trial, patients’ ON-Time—a period where Parkinson’s medications like levodopa bring about good motor control—increased by 65% over two years, and OFF-Time decreased by 55% within the same period, the company reported in June 2021. The cells were well-tolerated with no serious adverse events. With therapies such as these, Kirkeby said it is possible that the cells could overgrow and generate too many cells in the brain, but so far, neither trials of STEM-PD nor bemdaneprocel have recorded this adverse effect. And while stem cell therapies are currently aimed at relieving the motor symptoms of Parkinson’s, Enayetallah said bemdaneprocel’s trial results hint at improved quality of life and psychiatric outcomes. Kirkeby also indicated that her lab is working on stem cell therapies that would target non-motor symptoms such as cognitive impairment. Enayetallah noted that therapeutic development in Parkinson’s is “incredibly challenging” and plagued with the highest failure rates in drug development. However, he said, the results of BlueRock’s Phase I trial are a significant step toward bringing a “transformational therapy” to patients. “Cell therapy in neurology is something that hasn’t been explored to that extent before. We’re paving the road here.” Patience Asanga is a Nigeria-based freelance science journalist who writes about the environment, biotechnology and life sciences.