Latest news with #NfL
Korea Herald
3 days ago
- Business
- Korea Herald
Neuronata-R® Stem Cell Therapy Shows Promise in ALS Phase 3 Subgroup Analysis, Moves Toward FDA Accelerated Approval
Meaningful efficacy observed in slow-progressor subgroup; NfL biomarker improvements support potential for accelerated regulatory pathway SEOUL, South Korea, May 29, 2025 /PRNewswire/ -- Neuronata-R®, an autologous bone marrow-derived mesenchymal stem cell (MSC) therapy for amyotrophic lateral sclerosis (ALS), has demonstrated meaningful efficacy signals in a subgroup of participants with slow disease progression in its recently completed Phase 3 trial. The therapy also showed consistent reductions in neurofilament light chain (NfL) levels — a biomarker that served as the basis for FDA accelerated approval in ALS, including the recent decision on Tofersen — supporting its potential to pursue a similar regulatory pathway. Developed by South Korean biotech company CorestemChemon (KOSDAQ: 166480), Neuronata-R® utilizes MSCs derived from a participant's own bone marrow to modulate inflammation, protect motor neurons, and alter the neurodegenerative microenvironment through paracrine signaling. ALS, a rare and fatal disease with no cure, remains one of the most urgent areas of unmet medical need. Neuronata-R® aims to address the disease's complex pathology by leveraging the therapeutic potential of autologous MSCs. In December 2024, CorestemChemon announced topline results from the ALSummit trial (NCT04745299), noting that the study did not meet its primary endpoint — a combined assessment of function and survival known as CAFS — in the overall patient population. However, a post hoc analysis conducted after the completion of the trial and full data collection revealed significant clinical improvements in a subgroup of patients with slower disease progression. To discuss these findings, the company plans to meet with the U.S. Food and Drug Administration (FDA) later this year to discuss these findings, with the aim of submitting a biologics license application by the end of 2025 and potentially securing accelerated approval by mid-2026. Subgroup Analysis Supports Targeted Efficacy The final Clinical Study Report (CSR) confirmed that Neuronata-R® demonstrated statistically significant improvements in key efficacy endpoints among participants with slow disease progression. Recognizing the potential efficacy of Neuronata-R® in early-stage ALS, CorestemChemon stratified participants into slow and fast progressors. Among slow progressors, Neuronata-R® showed statistically significant improvements across multiple measures — including the primary composite endpoint, CAFS (Combined Assessment of Function and Survival), functional outcomes assessed by ALSFRS-R scores, and respiratory function measured by slow vital capacity (SVC). Notably, the five-dose treatment arm (Group 2) demonstrated statistically significant improvement in ALSFRS-R scores beginning at Month 9 post-treatment — one month earlier than the two-dose arm (Group 1), which reached significance at Month 10. This final CSR also included full analyses of CAFS and SVC, which had not been previously disclosed. While CAFS served as the trial's primary efficacy endpoint, SVC is recognized as a clinically meaningful measure of respiratory decline in ALS. At Month 6, participants in Group 1 receiving Neuronata-R® showed a statistically significant improvement in CAFS (LS Mean 20.95 vs 13.66; 95% CI; p<0.024) compared with placebo. Group 2 also showed improvement (LS Mean 24.78 vs 17.92; 95% CI; p<0.041). In Group 2, significant divergence in SVC compared to the control group emerged from Month 8 post-treatment, suggesting a potential effect in delaying disease progression. NfL Biomarker Reduction Mirrors Regulatory Precedent CorestemChemon also highlighted the reduction in NfL levels — a biomarker that served as the basis for FDA accelerated approval in ALS, including the recent decision on Tofersen. In both the two-dose (Group 1) and five-dose (Group 2) arms, NfL levels consistently declined over time. Notably, in Group 2, NfL levels were significantly lower than placebo at both Month 4 and Month 10, suggesting a potential dose-dependent effect. The consistency between the company's internal analysis and validation by an independent CRO strengthens the reliability of the dataset, which has been incorporated into the final CSR. "This subgroup analysis lends strong support to a biomarker-driven approval strategy," a company official said. "The consistency of our internal analysis with external CRO validation adds credibility to the dataset and provides a concrete basis for regulatory discussions with the MFDS." Regulatory Pathway Toward Accelerated Approval The company views these findings as strategically significant, particularly in light of their alignment with the precedent set by Tofersen, where the FDA granted accelerated approval based on NfL reduction rather than survival benefit — a pathway CorestemChemon now seeks to pursue. The company plans to request a Pre-BLA or Type C meeting with the FDA in Q3 2025, with the goal of submitting a biologics license application by Q4 2025 and targeting regulatory approval by mid-2026. CorestemChemon will finalize its submission package in collaboration with a global CRO and actively engage with regulatory agencies to pursue worldwide market entry for Neuronata-R®. Innovative Stem Cell Therapy Neuronata-R® uniquely addresses the complex mechanisms of ALS by leveraging MSCs derived from the patient's own bone marrow. These cells exert anti-inflammatory and immunomodulatory effects, protect motor neurons, and, through paracrine signaling, secrete trophic factors, cytokines, and extracellular vesicles that modulate the microenvironment and reduce neuroinflammation. By targeting these underlying pathological processes, Neuronata-R ® is designed to interrupt the neurodegenerative cascade. About Neuronata-R® Neuronata-R® (Lenzumestrocel), developed and commercialized by CorestemChemon Inc. (KOSDAQ: 166480), is an autologous MSC therapy for ALS patients. The company began ALS research in 2002 and obtained MFDS approval for Neuronata-R® in 2014. To date, it has been administered to more than 400 commercial patients and 190 clinical trial participants with no treatment-related serious adverse events reported. Neuronata-R® holds Orphan Drug Designation from both the U.S. FDA (2018) and the EMA (2019). CorestemChemon completed a Phase 2 trial (NCT01363401) in 2014 and its Phase 3 trial (NCT04745299) in 2024; the final CSR has been submitted to the MFDS.
Yahoo
11-04-2025
- Health
- Yahoo
Brains of people with schizophrenia may age faster – how our research adds to the evidence
What causes schizophrenia? This severe mental illness, which affects over 20 million people worldwide and is characterised by recurrent hallucinations and delusions, often begins to emerge in the period from adolescence to early adulthood. It's a complex disorder that affects almost every area of life. Current theories about why schizophrenia develops suggest it may be linked to changes in brain development during this critical period of emerging adulthood. Schizophrenia is also thought to be similar to conditions such as dyslexia, autism and attention deficit hyperactivity disorder (ADHD), which are neurodevelopmental but usually manifest in childhood. However, our research suggests that accelerated brain ageing could be another potential driver in the development of schizophrenia – and this can be measured using a simple blood test. Our study is unique because we measured proteins in blood derived directly from brain neurons – the brain's nerve cells – in people suffering from schizophrenia. This protein, called neurofilament light protein (NfL), consists of long, thread-like structures that help maintain the size and shape of nerve cells. NfL is released into the blood and cerebrospinal fluid when brain neurons are damaged or undergo neurodegeneration. Its release when these cells are damaged makes it a useful biomarker for diagnosing and monitoring neurodegenerative diseases and neurological damage. Measuring the levels of NfL can also provide insight into the extent of neuronal injury. Get your news from actual experts, direct to your inbox. Sign up to our daily newsletter to receive all The Conversation UK's latest coverage of news and research, from politics and business to the arts and sciences. Join The Conversation for free today. Neuronal injury is damage or harm to neurons, the specialised cells in the nervous system essential for communication in the brain, spinal cord and peripheral nervous system. When neurons are injured, their ability to function properly is impaired, which can result in a range of neurological symptoms depending on the severity and location of the damage. Raised levels of NfL have been associated with a range of neurological conditions including Alzheimer's disease, multiple sclerosis, Parkinson's disease and frontotemporal dementia. But NfL levels also normally increase with age as these proteins lose the ability to repair themselves as effectively. This is due to a combination of factors including gradual wear-and-tear on neurons over time. While reductions in the brain's grey matter, white matter and connectivity are all part of normal, healthy ageing, these changes are usually gradual and not disabling. Grey matter contains most of the brain's neurons and is responsible for processing information, memory, decision-making, muscle control, and seeing and hearing. White matter is the long fibres that connect different brain regions, allowing them to communicate quickly and efficiently. Noticeable symptoms of normal, healthy brain ageing might include a bit more forgetfulness, slower reaction time, and difficulty juggling multiple tasks. Such changes are very different from the patterns seen in illnesses like schizophrenia where, our study shows, the decline is faster and more severe, indicating an older brain age than would be expected from the patient's chronological age. Our research found that, in people with schizophrenia, NfL levels appeared to increase more quickly with age, compared with the rate of increase in healthy people, indicating an acceleration of the brain ageing process. We also studied samples from people suffering from bipolar disorder, which did not show the same accelerated increase. Data from other methods, such as calculating 'brain age' from MRI scans, also points to accelerated brain ageing in people with schizophrenia. For people suffering from schizophrenia, accelerated ageing of the body is already a serious problem, as Christos Pantelis, a Melbourne psychiatrist and senior author of our study, explains: An important problem is that people with chronic schizophrenia are often exposed to an unhealthy lifestyle overall. They can experience isolation, unemployment, lack of physical activities, smoking – and many resort to illicit drug use that can make their condition worse. Currently, people diagnosed with schizophrenia have a life expectancy 20-30 years shorter than the average. This is mainly due to earlier development of common age-related diseases such as cancer and cardiovascular disease. Around half of people with schizophrenia have at least one other chronic medical condition, such as obesity, respiratory conditions, chronic pain and substance-use disorders. People with schizophrenia have a higher risk of substance-use disorders due to a combination of biological, psychological and environmental factors. These include self-medication for distressing symptoms, impaired cognitive function, social isolation, and difficulties with treatment adherence. While lifestyle is a factor in the accelerated ageing of the body for those living with schizophrenia, our study could prove another important step in understanding – and in time, treating – this distressing disease. This article is republished from The Conversation under a Creative Commons license. Read the original article. Alexander F Santillo primarily receives funding from the Swedish federal government under the ALF agreement. Cassandra Wannan receives funding from the National Health and Medical Research Council. Dhamidhu Eratne receives funding from the Australian National Health and Medical Research Council.
Yahoo
02-04-2025
- Health
- Yahoo
Iron in The Brain Might Help Explain Curious Link Between ADHD And Dementia
Older adults with ADHD are at higher risk of age-related dementias like Alzheimer's disease, and an international team of neuroscientists has found a lead on why this might be the case. Led by medical physicist Jatta Berberat from the University of Geneva, the team has discovered that iron is distributed similarly in the brains of people with these associated disorders, which may help to explain the link. There's good evidence that as the human brain ages, it continuously accumulates iron, in both the neocortex (which accounts for about 90 percent of our cerebral cortex) and in the quarter of our brain that sits below the cortex, including the hippocampus, the cerebellum, the amygdala and the basal ganglia. "Excess iron in certain regions of the brain is often observed [in neurodegenerative diseases] and is associated with increased oxidative stress that furthers neuronal degeneration," explains psychiatrist Paul Unschuld from Geneva University Hospitals. When iron levels build up in these regions, cognitive performance drops. Quite a few studies have found people with neurodegenerative diseases, including Huntington's, Parkinson's, and Alzheimer's, have noticeably high levels of brain iron, which, because of its magnetic properties, can quite easily be detected by MRI scanners. The team used this technique to map the layout of accumulated iron in the brains of 32 adults with ADHD, and 29 others without the condition. The team also took blood samples to measure neurofilament light chain protein (NfL) levels, a protein released when axons are damaged or degenerate. At high levels in blood, NfL indicates damage to the neuronal axons that carry information to neighbouring nerves, and is a potential biomarker for dementia. Finally, study participants answered questions related to ADHD symptoms and lifestyle factors. Each facet of this small study was designed to pick up on patterns that may distinguish an ADHD brain by its iron, and look for an association with neuronal axon damage signifying neurodegeneration to indicate whether scientists should pursue this track further. The MRI-based maps suggest this is no dead end. Participants with ADHD had a distinct distribution of brain iron, with particularly elevated levels in the precentral cortex and a number of other regions. The iron landscape of ADHD brains was different enough from the non-ADHD group to be considered significant. The researchers also found a significant association between raised iron levels in the precentral cortex of ADHD participants, and NfL levels in their blood. This could mean a build-up of brain iron deposits is creating a communication break-down in the area of the brain responsible for pulling the strings on the rest of the body. Of the ADHD participants, 19 were taking regular medication for the condition, either methylphenidate (Ritalin) or dexamphetamine. Some scientists suspect long-term use of psychostimulant medications like these could be behind the ADHD dementia link, because recreational stimulant drugs like MDMA and cocaine are known to affect brain iron levels. Other studies suggest ADHD medication may normalize brain iron in people with ADHD, but long-term effects remain unclear. Unfortunately, this particular study is too small (and was not designed) to tell us if ADHD medications are actively involved in the tangle of associations, or if they're just innocent bystanders trying to help. Nonetheless, Unschuld hopes the findings will lead to targeted dementia risk reduction strategies for people diagnosed with ADHD later in life. "This is especially important since there is a well-known correlation between lifestyle and altered iron levels in the brain," he says. "To achieve this, additional longitudinal studies are required in order to determine if a reduction of iron levels in the brain is a potential treatment pathway for preventing dementia at an advanced age in persons with ADHD." This research was published in Psychiatry and Clinical Neurosciences. Measles Devastates Your Body in a Variety of Ways. Here's What's at Risk. Vitamin D Could Be an Effective Way to Slow Progress of MS Protein That Calms Waking Hair Follicles Could Lead to Alopecia Treatment
