Seminars in Nuclear Medicine, Год журнала: 2025, Номер unknown
Опубликована: Апрель 1, 2025
Язык: Английский
Alzheimer s & Dementia, Год журнала: 2024, Номер 20(11), С. 8129 - 8152
Опубликована: Сен. 24, 2024
The tauopathies are defined by pathological tau protein aggregates within a spectrum of clinically heterogeneous neurodegenerative diseases. primary meet the definition rare diseases in United States. There is no approved treatment for tauopathies. In this context, designing most efficient development programs to translate promising targets and treatments from preclinical studies early-phase clinical trials vital. September 2022, Rainwater Charitable Foundation convened an international expert workshop focused on translation tauopathy therapeutics through trials. Our report recommends framework principled drug companion lexicon facilitate communication focusing reproducibility achieving common elements. Topics include selection targets, drugs, biomarkers, participants, study designs. maturation pharmacodynamic biomarkers demonstrate target engagement surrogate disease crucial unmet need. HIGHLIGHTS: Experts provided (discovery trials). "5 Rights" (target, drug, biomarker, trial). Current research frontotemporal degeneration, progressive supranuclear palsy, corticobasal syndrome includes 32 (37% biologics) Tau being tested Alzheimer's disease; have large
Язык: Английский
Процитировано
6
Journal of Parkinson s Disease, Год журнала: 2025, Номер unknown
Опубликована: Фев. 2, 2025
Cognitive impairment is a common non-motor symptom in people with Parkinson's disease (PD) and associated to poor clinical outcomes. Currently, rivastigmine the only approved medication for PD dementia, there are no treatments available mild cognitive impairment. To advance pharmacological management of PD, it essential optimize trial design. This includes refining outcome measures, ensuring longer study durations, incorporating PD-specific assessments. Biomarkers offer valuable opportunities screening, stratification, enrichment, monitoring trials, increasing likelihood detecting treatment effects. Additionally, adopting patient-centered approaches that prioritize inclusivity can enhance validity address current lack diversity studies. Digital assessments promising tool improving participation enabling longitudinal monitoring, especially underrepresented mobility-challenged populations. By tackling these challenges, this review outlines strategies advancing PD. It emphasizes need precise, inclusive, biomarker-driven trials accelerate drug development.
Язык: Английский
Процитировано
0
ChemMedChem, Год журнала: 2025, Номер unknown
Опубликована: Март 27, 2025
Abstract Progressive Supranuclear Palsy (PSP) is a rare neurodegenerative disorder characterized by abnormal tau protein accumulation. This perspective article explores AZP2006 (INN: Ezeprogind), novel small molecule targeting the Progranulin (PGRN) and Prosaposin (PSAP) axis to enhance lysosomal health in PSP treatment. stabilizes PGRN‐PSAP complex, improving function reducing pathology. Preclinical studies tauopathy models demonstrated AZP2006′s ability decrease hyperphosphorylation, neuronal survival, mitigate neuroinflammation promote synaptogenesis. Clinical trials have shown be well‐tolerated healthy volunteers patients. A Phase 2a study met its primary endpoints, as it provided valuable safety data even encouraged further investigation of efficacy larger clinical study. An upcoming 2b/3 trial aims assess long‐term cohort. mechanism action strongly suggests potential applications other tauopathies, including Alzheimer's Parkinson's diseases. By addressing dysfunction pathology, represents promising disease‐modifying approach for disorders.
Язык: Английский
Процитировано
0
Biology, Год журнала: 2025, Номер 14(4), С. 349 - 349
Опубликована: Март 27, 2025
The Constrained Disorder Principle (CDP) offers a new framework for understanding how biological systems use and manage noise to maintain optimal functionality. This review explores the relationship between at various scales, including genetic, cellular, organ levels, its implications system malfunctions. According CDP, all require an range of function appropriately, disease states can arise when these levels are disrupted. presents evidence supporting this principle across different contexts, such as genetic variability, cellular behavior, brain functions, human aging, evolution, drug administration. For accurate clinical assessments, it is essential distinguish technical variability intrinsic variability. When adequately constrained, serves fundamental mechanism adaptation functioning rather than simply source disruption. These findings have important developing more effective therapeutic strategies systems’ dynamics. CDP-based second-generation artificial intelligence help regulate address improved outcomes in conditions by incorporating controlled randomness. Understanding patterns has significant diagnosis, treatment monitoring, development medical conditions.
Язык: Английский
Процитировано
0
Nature Reviews Drug Discovery, Год журнала: 2025, Номер unknown
Опубликована: Апрель 4, 2025
Язык: Английский
Процитировано
0
Seminars in Nuclear Medicine, Год журнала: 2025, Номер unknown
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0