Latest news with #CIAS
BBC News
13 hours ago
- Climate
- BBC News
Channel Island search and rescue issues summer warning
Channel Islands Air Search (CIAS) is urging people to take extra care on the coast as people experience the hot voluntary airborne search and rescue service, which operates in Channel Island waters, has taken to social media to warn to of the dangers the sea can hold for unsuspecting sunseekers. CIAS said it wanted to make sure everyone followed a few basic, but important tips - whether they were swimming, paddleboarding, boating or simply enjoying the views."It's essential to stay safe while soaking up the sun because we don't want your summer adventures to end in distress," said a spokesperson. The advice to swimmers included staying visible in the water by wearing bright swim caps or floats to be visible to potential were advised to check that their vessel was seaworthy and fully equipped before setting off across the waves, while telling someone your route beforehand would limit the potential search area should anyone get lost. Staying hydrated and avoiding overexposure to the sun, especially during physical activity, was another good way of ensuring a day out does not end in disaster. CIAS said it received callouts all year round at any time of day and responded to a record number last to incidents across 4,000 sq miles (6,437 sq km) of water, the team also revealed in its recent annual report that it had become twice as busy generally in one callout every 11.4 days, its missions ranged from locating missing people inland to overdue vessels at sea.
Ottawa Citizen
28-04-2025
- Health
- Ottawa Citizen
Alto Neuroscience Presents New Data at the Society of Biological Psychiatry Annual Meeting Underscoring Precision Psychiatry Approach
Article content – Identified and prospectively replicated an EEG-based biomarker for placebo response in MDD – Article content Article content – New data strengthen the mechanistic link between ALTO-300 and the EEG biomarker being used for patient selection; biomarker signature induced by activating 5-HT2C or depleting dopamine directly – Article content – Preclinical ALTO-101 rescue study underscores the therapeutic potential of this novel PDE4 inhibitor, and validates EEG theta response as a robust translational biomarker for CIAS – Article content Article content MOUNTAIN VIEW, Calif. — Alto Neuroscience, Inc. ('Alto') (NYSE: ANRO) a clinical-stage biopharmaceutical company focused on the development of novel precision medicines for neuropsychiatric disorders, today announced multiple presentations at the Society of Biological Psychiatry (SOBP) Annual Meeting, in Toronto, Canada, held April 24-26, 2025. Article content 'The biological and clinical insights we presented at SOBP support our precision psychiatry pipeline and mark important advancements for the field,' said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. 'To address the longstanding challenge of high placebo response in neuropsychiatric clinical development, we have successfully identified and prospectively replicated an EEG biomarker that captures placebo response patterns in patients with major depressive disorder. We believe this biomarker has the potential to reduce noise and improve the detection of true therapeutic effect.' Article content Dr. Etkin continued, 'We enhanced our understanding of the mechanistic link between ALTO-300 and the machine-learning derived, EEG biomarker used to identify patients who are more likely to respond to treatment. We showed that increasing 5-HT2C activity or directly depleting dopamine—both the opposite mechanistic effect of ALTO-300—resulted in greater EEG irregularity, consistent with a biomarker positive profile. Additionally, in a preclinical rescue study we demonstrated that ALTO-101 increased theta response, demonstrating its robustness as a translational biomarker for cognitive impairment associated with schizophrenia and potential pro-cognitive drug effect. We look forward to leveraging these findings to drive meaningful innovation in psychiatry and enhance clinical outcomes for patients.' Article content Background and Rationale: High placebo response is a major challenge in clinical trials for patients with major depressive disorder (MDD), yet no validated biomarker exists for reliably identifying high placebo responders. A shared predictor across diverse established antidepressant treatments was hypothesized to approximate a placebo response. Prospective replication was conducted in two randomized trials, including placebo and active arms. Within the two randomized trials, the ability to increase drug-placebo effect size was evaluated by incorporating placebo response predictions as sample weights. Key Takeaways: An EEG-based biomarker capable of predicting non-specific treatment response across multiple interventions and independent datasets was developed and validated. The placebo biomarker yielded significant predictions for the open-label ALTO-100 and sertraline treatment response, both analyzed prospectively. Additional prospective analyses in two randomized-controlled MDD studies were conducted to further validate the previously identified EEG-based placebo biomarker (ALTO-100 Phase 2b trial and the EMBARC sertraline trial) on both placebo response and drug-placebo differences. In the ALTO-100 placebo arm, the biomarker significantly predicted MADRS score change across all weeks with correlation ranging from 0.29 to 0.19 (p=0.001 to p=0.029; Cohen's d=0.49 to d=0.41) at weeks 2 and 6 respectively. In the EMBARC placebo arm, the biomarker significantly predicted HAMD score change, with a partial correlation ranging from 0.24 to 0.31 (p=0.009 to p=0.001) at weeks 6 and 8 respectively. Drug-placebo treatment effect sizes were enhanced across diverse drug mechanisms when accounting for individual differences in predicted placebo response, as demonstrated by both the Phase 2b trial of ALTO-100 and EMBARC trial of sertraline. This biomarker has the potential to enable more precise identification of high placebo responders in MDD trials, reduce trial variability, and enhance detection of treatment effects. Intellectual Property: Alto has patent protection covering the use of EEG biomarkers to predict placebo response. Article content Background and Rationale: ALTO-300 is an oral, small molecule designed to act as a melatonin agonist and 5-HT2C antagonist. ALTO-300 has been shown to enhance dopaminergic and noradrenergic input to the frontal cortex and rescue anhedonia-like behavioral deficits. Greater gamma sample entropy (SE), or EEG irregularity, was previously shown to predict antidepressant response to ALTO-300 in MDD. Increasing 5-HT2C activity or directly depleting dopamine (both the opposite mechanism of ALTO-300) was hypothesized to increase gamma SE and create a more biomarker positive EEG pattern. Key Takeaways: Administered two different 5-HT2C agonists (R0-0175 and YM348) in independent preclinical studies and revealed a dose-related increase in SE. 5-HT2C agonism also led to an anhedonic phenotype as demonstrated by a sucrose preference test. In a double-blind, placebo-controlled, cross-over study, healthy participants consumed a nutritionally balanced amino acid mixture (placebo) and a mixture deficient in the dopamine precursors tyrosine and phenylalanine (APTD) in a counterbalanced order. SE was significantly larger in the APTD condition compared to the placebo condition (p<0.01, Cohen's d=0.94), indicating that dopamine depletion drives a biomarker positive EEG pattern. The ALTO-300 biomarker signal likely reflects increased neural noise due to elevated 5-HT2C tone and reduced dopaminergic activity. The mechanism of action of ALTO-300 involves an increase in dopamine in part through 5-HT2C antagonism. These findings therefore provide a direct link between ALTO-300 and the EEG biomarker used to identify MDD patients who are more likely to be responders to treatment. Article content Background and Rationale: Cognitive Impairment Associated with Schizophrenia (CIAS) remains a high unmet need, with no approved treatments specifically targeting these deficits. Theta EEG response, measured by inter-trial coherence (ITC), is reproducibly disrupted in patients with schizophrenia and was previously identified as a promising marker for CIAS. Theta response strongly correlated with cognitive deficits in patients in multiple datasets. N-methyl-D-aspartate receptor (NMDAR) hypofunction plays a key role in CIAS pathophysiology. A rodent model was used to evaluate the effects of ALTO-101 on theta response following administration of MK-801, an NMDAR antagonist. Key Takeaways: Administration of MK-801 reduced theta response, modeling neural and behavioral abnormalities in schizophrenia. Administration of ALTO-101 led to a dose-dependent rescue of the theta response abnormality induced by MK-801 and was statistically significant at the highest dose of 0.1 mg/kg (p<0.001). Results are consistent with the completed Phase 1 trial in healthy volunteers, where ALTO-101 demonstrated robust, dose-dependent effects on theta response and cognitive test performance. The effects on these two measures were also correlated. Taken together, results validate theta response as a robust translational biomarker and underscore the potential cognitive benefits of ALTO-101 for patients with CIAS.
National Post
28-04-2025
- Health
- National Post
Alto Neuroscience Presents New Data at the Society of Biological Psychiatry Annual Meeting Underscoring Precision Psychiatry Approach
Article content – Identified and prospectively replicated an EEG-based biomarker for placebo response in MDD – Article content Article content – New data strengthen the mechanistic link between ALTO-300 and the EEG biomarker being used for patient selection; biomarker signature induced by activating 5-HT2C or depleting dopamine directly – Article content – Preclinical ALTO-101 rescue study underscores the therapeutic potential of this novel PDE4 inhibitor, and validates EEG theta response as a robust translational biomarker for CIAS – Article content Article content MOUNTAIN VIEW, Calif. — Alto Neuroscience, Inc. ('Alto') (NYSE: ANRO) a clinical-stage biopharmaceutical company focused on the development of novel precision medicines for neuropsychiatric disorders, today announced multiple presentations at the Society of Biological Psychiatry (SOBP) Annual Meeting, in Toronto, Canada, held April 24-26, 2025. Article content 'The biological and clinical insights we presented at SOBP support our precision psychiatry pipeline and mark important advancements for the field,' said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. 'To address the longstanding challenge of high placebo response in neuropsychiatric clinical development, we have successfully identified and prospectively replicated an EEG biomarker that captures placebo response patterns in patients with major depressive disorder. We believe this biomarker has the potential to reduce noise and improve the detection of true therapeutic effect.' Article content Dr. Etkin continued, 'We enhanced our understanding of the mechanistic link between ALTO-300 and the machine-learning derived, EEG biomarker used to identify patients who are more likely to respond to treatment. We showed that increasing 5-HT2C activity or directly depleting dopamine—both the opposite mechanistic effect of ALTO-300—resulted in greater EEG irregularity, consistent with a biomarker positive profile. Additionally, in a preclinical rescue study we demonstrated that ALTO-101 increased theta response, demonstrating its robustness as a translational biomarker for cognitive impairment associated with schizophrenia and potential pro-cognitive drug effect. We look forward to leveraging these findings to drive meaningful innovation in psychiatry and enhance clinical outcomes for patients.' Article content Background and Rationale: High placebo response is a major challenge in clinical trials for patients with major depressive disorder (MDD), yet no validated biomarker exists for reliably identifying high placebo responders. A shared predictor across diverse established antidepressant treatments was hypothesized to approximate a placebo response. Prospective replication was conducted in two randomized trials, including placebo and active arms. Within the two randomized trials, the ability to increase drug-placebo effect size was evaluated by incorporating placebo response predictions as sample weights. Key Takeaways: An EEG-based biomarker capable of predicting non-specific treatment response across multiple interventions and independent datasets was developed and validated. The placebo biomarker yielded significant predictions for the open-label ALTO-100 and sertraline treatment response, both analyzed prospectively. Additional prospective analyses in two randomized-controlled MDD studies were conducted to further validate the previously identified EEG-based placebo biomarker (ALTO-100 Phase 2b trial and the EMBARC sertraline trial) on both placebo response and drug-placebo differences. In the ALTO-100 placebo arm, the biomarker significantly predicted MADRS score change across all weeks with correlation ranging from 0.29 to 0.19 (p=0.001 to p=0.029; Cohen's d=0.49 to d=0.41) at weeks 2 and 6 respectively. In the EMBARC placebo arm, the biomarker significantly predicted HAMD score change, with a partial correlation ranging from 0.24 to 0.31 (p=0.009 to p=0.001) at weeks 6 and 8 respectively. Drug-placebo treatment effect sizes were enhanced across diverse drug mechanisms when accounting for individual differences in predicted placebo response, as demonstrated by both the Phase 2b trial of ALTO-100 and EMBARC trial of sertraline. This biomarker has the potential to enable more precise identification of high placebo responders in MDD trials, reduce trial variability, and enhance detection of treatment effects. Intellectual Property: Alto has patent protection covering the use of EEG biomarkers to predict placebo response. Article content Background and Rationale: ALTO-300 is an oral, small molecule designed to act as a melatonin agonist and 5-HT2C antagonist. ALTO-300 has been shown to enhance dopaminergic and noradrenergic input to the frontal cortex and rescue anhedonia-like behavioral deficits. Greater gamma sample entropy (SE), or EEG irregularity, was previously shown to predict antidepressant response to ALTO-300 in MDD. Increasing 5-HT2C activity or directly depleting dopamine (both the opposite mechanism of ALTO-300) was hypothesized to increase gamma SE and create a more biomarker positive EEG pattern. Key Takeaways: Administered two different 5-HT2C agonists (R0-0175 and YM348) in independent preclinical studies and revealed a dose-related increase in SE. 5-HT2C agonism also led to an anhedonic phenotype as demonstrated by a sucrose preference test. In a double-blind, placebo-controlled, cross-over study, healthy participants consumed a nutritionally balanced amino acid mixture (placebo) and a mixture deficient in the dopamine precursors tyrosine and phenylalanine (APTD) in a counterbalanced order. SE was significantly larger in the APTD condition compared to the placebo condition (p<0.01, Cohen's d=0.94), indicating that dopamine depletion drives a biomarker positive EEG pattern. The ALTO-300 biomarker signal likely reflects increased neural noise due to elevated 5-HT2C tone and reduced dopaminergic activity. The mechanism of action of ALTO-300 involves an increase in dopamine in part through 5-HT2C antagonism. These findings therefore provide a direct link between ALTO-300 and the EEG biomarker used to identify MDD patients who are more likely to be responders to treatment. Article content Background and Rationale: Cognitive Impairment Associated with Schizophrenia (CIAS) remains a high unmet need, with no approved treatments specifically targeting these deficits. Theta EEG response, measured by inter-trial coherence (ITC), is reproducibly disrupted in patients with schizophrenia and was previously identified as a promising marker for CIAS. Theta response strongly correlated with cognitive deficits in patients in multiple datasets. N-methyl-D-aspartate receptor (NMDAR) hypofunction plays a key role in CIAS pathophysiology. A rodent model was used to evaluate the effects of ALTO-101 on theta response following administration of MK-801, an NMDAR antagonist. Key Takeaways: Administration of MK-801 reduced theta response, modeling neural and behavioral abnormalities in schizophrenia. Administration of ALTO-101 led to a dose-dependent rescue of the theta response abnormality induced by MK-801 and was statistically significant at the highest dose of 0.1 mg/kg (p<0.001). Results are consistent with the completed Phase 1 trial in healthy volunteers, where ALTO-101 demonstrated robust, dose-dependent effects on theta response and cognitive test performance. The effects on these two measures were also correlated. Taken together, results validate theta response as a robust translational biomarker and underscore the potential cognitive benefits of ALTO-101 for patients with CIAS.
