Novel Method for Diagnosis of Neurodegenerative Diseases Based on Saliva Biochemical Profiling
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 242
- 试验地点
- 5
- 主要终点
- Salivary Raman fingerprint of AD, PD, AtPD, prodromal PD and MCI
研究概览
简要总结
Early diagnosis of Neurodegenerative diseases (NDDs) and accurate patient profiling are key goals needed to tailor prompt personalized therapeutic strategies that can significantly impact disease progression and patients' quality of life. The project will validate a novel, cost-effective and quick biophotonic-based method for early and differential diagnosis of NDDs (Parkinson's disease, atypical parkinsonisms, Alzheimer's disease) and for routine clinical monitoring of NDD progression (longitudinal study). Raman spectroscopy (RS) will be applied to biochemically profile saliva and salivaderived Extracellular Vesicles (sEVs) and to identify a spectroscopic biomarker for NDDs. Optimized protocols for RS will be used to concomitantly evaluate saliva and sEVs from people with NDDs and to detect salivary changes in the biochemical profile, with special focus on EV-associated components. The accuracy of the method in discriminating NDDs at different disease stages and during disease progression will be verified. A nanotechnology-based biomolecular characterization of saliva and sEV will clarify the involvement of specific pathological molecules in NDDs progression.
详细描述
BACKGROUND: Neurodegenerative diseases (NDDs) are a miscellaneous group of disorders that variably affect individuals, with many subtle distinctions and different speeds across individuals and syndromes. The evolution of NDDs involves cognition, behavior and motor domains of clinical assessment that result in lifelong functional and social impairments with high economic and social costs. The biochemical pathophysiological drivers occur far earlier than symptoms appearance making the identification of subjects with preclinical disease the basis for early diagnosis, needed for an effective therapy.
The clinical definition of NDDs is basically insufficient, but the molecular signals from the brain can lead to the identification of a biomarker that can be measured periodically in a non-invasive way. Therefore, a disease-specific biomarker is needed.
The possibility of identifying specific markers for NDDs within saliva has recently emerged. Saliva and salivary Extracelluler Vesicles (sEVs) are vehicles for molecules associated with neuronal damage and neuroinflammation. Their isolation allows an enrichment of the molecules involved in the pathogenetic mechanisms of NDDs, improving their quantification.
Raman spectroscopy (RS) is a method useful for the exhaustive biochemical characterization of saliva and its vesicular component, without staining and labeling procedures, highly informative, rapid and sustainable. In a rapid, sensitive and non-destructive way, RS provides with a spectrum that can be used as a highly specific "fingerprint" for the selected sample (e.g. saliva, blood, EV) representing the diagnostic biomarker itself.
The RS study of saliva has already demonstrated the possibility of profiling patients with progressive pathologies with good accuracy and, specifically, of distinguishing subjects suffering from NDDs, with no further investigation of the ability to distinguish the NDDs at an early stage, the verification of the possibility to monitor its progression, nor the investigation of the biomolecular moieties involved in the observed differences.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •AD: standard criteria for dementia due to AD with AD neurochemical demonstration.
- •PD: MDS Criteria; modified Hoehn&Yahr stages; stable pharmacological treatment (last 4 weeks).
- •AtP: current consensus diagnostic criteria for progressive supranuclear palsy; corticobasal degeneration and multiple system atrophy.
- •prodromic PD: according to diagnostic criteria by Berg;
- •MCI: according to diagnostic criteria by Dubois and Albert.
排除标准
- •For all the experimental groups considered, subjects with concomitant chronic and / or inflammatory diseases of the oral cavity, other systemic diseases, oncological or infectious diseases will be excluded.
- •Patients not able to provide written informed consent autonomously will be excluded.
- •For PD patients: Vascular, familiar and drug- induced parkinsonism, other known or suspected causes (metabolic, brain tumor etc) or any suggestive features of AtP; dementia with MoCA Test Correct Score<15
结局指标
主要结局
Salivary Raman fingerprint of AD, PD, AtPD, prodromal PD and MCI
时间窗: From the enrollment to the follow up evaluation and second sample collection at 12 months
Differences in the Raman spectra of saliva of patients with AD, PD, AtPD, prodromal PD and MCI in the spectral range 400-1800 cm-1
次要结局
- Raman fingerprint of salivary EV of AD, PD, AtPD, prodromal PD and MCI(From the enrollment to the follow up evaluation and second sample collection at 12 months)
- Salivary NDD biomarkers(From enrollment to follow up evaluation and second sample collection at 12 months)
- Salivary Raman fingerprint of patients after 1 year(From enrollment to follow up and second sample collection at 12 months)
- Salivary EV Raman fingerprint of patients after 1 year(From enrollment to follow up and second sample collection at 12 months)
- Correlation of Raman data with clinical assessment(From enrollment to follow up at 12 months)
- Correlation of Raman data with biomolecular data(From enrollment to follow up at 12 months)