- |||||||||| dexpramipexole (KNS-760704) / Areteia Therapeutics
Trial completion date, Trial primary completion date: EXHALE-5: Phase III Long-Term Extension Study With Dexpramipexole (clinicaltrials.gov) - Jun 12, 2025 P3, N=1600, Enrolling by invitation, Trial completion date: Jul 2026 --> May 2027 | Trial primary completion date: Jun 2026 --> Mar 2027 Trial completion date: Jun 2027 --> May 2028 | Trial primary completion date: Jun 2027 --> Mar 2028
- |||||||||| dexpramipexole (KNS-760704) / Areteia Therapeutics, belnacasan (VX-765) / Vertex
Review, Journal: Research progress on sepsis-associated encephalopathy by inhibiting pyroptosis. (Pubmed Central) - May 25, 2025 Therefore, they have significant importance in terms of brain protection. Moreover, we review the relevant literature published in recent years and summarize the research status and development prospects in this field to provide a basis for subsequent related research.
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Enrollment closed, Trial completion date, Trial primary completion date: SUSPIRE-1: A Study to Assess the Effects of Dexpramipexole in Participants With Eosinophilic COPD (clinicaltrials.gov) - May 14, 2025 P2, N=30, Active, not recruiting, Moreover, we review the relevant literature published in recent years and summarize the research status and development prospects in this field to provide a basis for subsequent related research. Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Apr 2025 --> Oct 2025
- |||||||||| dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen
Parkinson (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_12484; Finally, we show that small molecules previously shown to improve mitochondrial efficiency, such as honokiol and dexpramipexole, are protective against 6-OHDA and MPP+, respectively...This study demonstrates that cellular stressors have unique effects on axonal release sites, not all of which involve direct oxidative stress mechanisms. These discoveries enhance our comprehension of the mechanism of action of cellular stressors commonly used to model PD pathology and provide new insights into the development of neuroprotective agents through the optimization of bioenergetics and underscore the importance of considering the specificity of these cellular stressors.
- |||||||||| dexpramipexole (KNS-760704) / Areteia Therapeutics
Trial completion date, Trial primary completion date: A Study to Assess the Effect of Dexpramipexole in Adolescents and Adults With Severe Eosinophilic Asthma (EXHALE-3) (clinicaltrials.gov) - Feb 15, 2024 P3, N=930, Recruiting, These discoveries enhance our comprehension of the mechanism of action of cellular stressors commonly used to model PD pathology and provide new insights into the development of neuroprotective agents through the optimization of bioenergetics and underscore the importance of considering the specificity of these cellular stressors. Trial completion date: Dec 2025 --> Jul 2026 | Trial primary completion date: Nov 2025 --> Jun 2026
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A Novel Mitochondrial Target as a Therapeutic Approach to Bipolar Disorder (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_3303; We found that BD cortical organoid mitoplasts have larger peak conductances than those of HCs. Lithium, which is a long-term treatment for episodes of mania and depression, blocks ACLC in both BD and HC cortical organoid mitoplasts and appears to work synergistically with the known ATP synthase pharmacological modulator, dexpramipexole (Dex).
- |||||||||| dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen
FDA event, Preclinical, Journal, Immune cell: The clinically-approved compounds, pramipexole and dexpramipexole, reverse chronic allodynia from sciatic nerve damage in mice, and alter IL-1? and IL-10 expression from immune cell culture. (Pubmed Central) - Sep 25, 2023 protein production from stimulated human monocytes and dexpramipexole induced elevated IL-10 mRNA expression from rat splenocytes. The data support that clinically-approved compounds like pramipexole and dexpramipexole support their application as anti-inflammatory agents to mitigate chronic neuropathy, and provide a blueprint for future, multifaceted approaches for opioid-independent neuropathic pain treatment.
- |||||||||| dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen, Yale University
From abnormal metabolism to behavioral deficits-early postnatal intervention in Fragile X mice. (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_1413; We discovered that in Fragile X syndrome the pharmacological inhibition of ACLC by the ATP synthase modulator Dexpramipexole (Dex) normalizes the elevated protein translation rates and attenuates autistic behaviors, which raises the spectrum of new possibilities for therapeutic intervention...We hypothesize that modulation of ACLC at this time speeds metabolic development of the synapse with effects on specific protein synthesis, synaptic structure and connectivity, and this may normalize circuitry and produce behavioral benefits into adulthood. We are now testing this hypothesis.
- |||||||||| dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen, Yale University, Nucala (mepolizumab) / GSK, Fasenra (benralizumab) / AstraZeneca
Journal: Urine eosinophil-derived neurotoxin: a potential marker of activity in select eosinophilic disorders. (Pubmed Central) - Aug 18, 2022 Measurement of EGP in urine is non-invasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.
- |||||||||| dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen, Yale University
The Oral Eosinophil-lowering Drug Dexpramipexole Improves FEV1 Largely Thorough its Effect on FVC () - Feb 4, 2022 - Abstract #AAAAI2022AAAAI_1781; Dexpramipexole improves FEV1 measures of airflow obstruction in asthma largely through its effect on FVC and correlated to its effect on decreasing blood and airway eosinophils. These improvements in airflow obstruction suggest that eosinophils act luminally to promote air trapping, which can be overcome by decreasing eosinophils with dexpramipexole, possibly by diminishing airway mucus plugging.
- |||||||||| dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen
Biomarker, Enrollment change: AS201: Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma (clinicaltrials.gov) - Dec 22, 2021 P2, N=534, Completed, These improvements in airflow obstruction suggest that eosinophils act luminally to promote air trapping, which can be overcome by decreasing eosinophils with dexpramipexole, possibly by diminishing airway mucus plugging. N=103 --> 534
- |||||||||| dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen, Yale University
Mitochondrial inefficiency: from abnormal metabolism to behavioral deficits in Fragile X (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_306; We showed in Fragile X syndrome that pharmacological inhibition of ACLC by the ATP synthase modulator Dexpramipexole (Dex) normalizes the elevated protein translation rates, induces synaptic maturation, and attenuates autistic behaviors, which raises the spectrum of new possibilities for therapeutic intervention in FX...We find preliminarily that Dex alters the proximity of specific ATP synthase mRNAs to mitochondria, which could contribute to changes in ATP synthase stoichiometry by inducing assembly of ATP synthase and eliminating free c-subunit in the inner mitochondrial membrane. This stoichiometric alteration provides for a long-term change in the efficiency of ATP synthesis that may be required for normalization of behavioral abnormalities in Fragile X mice.; Grant Support: NIH: NS112706
- |||||||||| Journal: Advances in disease-modifying pharmacotherapies for the treatment of amyotrophic lateral sclerosis. (Pubmed Central) - Jul 29, 2020
To date, riluzole and edaravone are the only two drugs that have successfully passed clinical trials for the treatment of Amyotrophic Lateral Sclerosis (ALS)...To evolve toward more efficient therapies, we must conduct clinical trials with optimal stratification based on rapid/slow progressors and cognitive decline. Pharmaco-metabolomics should allow for the identification of biomarkers that are adapted for a given drug.
- |||||||||| dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen
Journal: Parkinson's disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth. (Pubmed Central) - Jul 19, 2020 This was ameliorated by a pharmacological reagent, dexpramipexole, that binds to ATP synthase, closing a mitochondrial inner membrane leak and enhancing ATP synthase efficiency...We found that ATP synthase β subunit protein level in the DJ-1 KO neurons was approximately half that found in their wild-type counterparts, comprising a severe defect in ATP synthase stoichiometry and unmasking c-subunit. We suggest that DJ-1 enhances dopaminergic cell metabolism and growth by its regulation of ATP synthase protein components.
- |||||||||| dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen
Review, Journal: Therapeutic strategies for eosinophilic dermatoses. (Pubmed Central) - Jun 26, 2020 Dexpramipexole and tyrosine kinase inhibitors have been shown to reduce eosinophil numbers in patients with hypereosinophilia...A further approach is to target cells and cytokines acting on or mediators released by eosinophils, for example, CD52, IL-13, IL-31, TSLP, and eotaxins. This review summarizes current therapeutic strategies, including novel agents affecting eosinophils directly that are under clinical investigation.
- |||||||||| dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen
Clinical, Journal: Increasing the efficiency of clinical trials in neurodegenerative disorders using group sequential trial designs. (Pubmed Central) - Sep 11, 2019 This review summarizes current therapeutic strategies, including novel agents affecting eosinophils directly that are under clinical investigation. Group sequential trials can result in important reductions in the trial duration, which could make clinical trials more ethical by reducing the patients' exposure to non-effective treatments or by limiting their time on placebo.
- |||||||||| dexpramipexole (KNS-760704) / Knopp Biosciences, Biogen
Biomarker, Enrollment open: AS201: Dexpramipexole Dose-Ranging Biomarker Study in Subjects With Eosinophilic Asthma (clinicaltrials.gov) - Aug 14, 2019 P2, N=100, Recruiting, Group sequential trials can result in important reductions in the trial duration, which could make clinical trials more ethical by reducing the patients' exposure to non-effective treatments or by limiting their time on placebo. Not yet recruiting --> Recruiting
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