Validation of a salivary miRNA diagnostic test for autism spectrum disorder

自闭症谱系障碍唾液 miRNA 诊断测试的验证

• 批准号: 10001004
• 负责人: Qian Du
• 金额: $ 62.2万
• 依托单位: QUADRANT BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001004
• 关键词: 3 year old; Adaptive Behaviors; Adopted; Affect; Age; Algorithms; American; Anoxic Encephalopathy; Autopsy; Behavior; Biological Markers; Biological Process; Biological Sciences; Blood; Brain; Cells; Characteristics; Child; Clinical; Clinical Trials; Collection; Communication; Communities; Consumption; DNA Sequence Alteration; Data; Detection; Development; Developmental Delay Disorders; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Early Intervention; Early treatment; Elements; Enrollment; Ensure; Environmental Risk Factor; Epigenetic Process; Etiology; Exhibits; Family; Future; Gene Expression; Genes; Genetic; Genetic Materials; Genetic Risk; Genetic Transcription; Genomics; Geography; Goals; Grant; Heterogeneity; Hormonal; Human; Human Microbiome; Incidence; Individual; Knowledge; Lead; Learning; Leukocytes; Link; Measurement; Measures; Medical; Methodology; Methods; MicroRNAs; Microbe; Mitochondria; Modeling; Monitor; Neuraxis; Neurodevelopmental Deficit; Neurologic; Neuropsychology; Only Child; Outcome; Oxidative Stress; Pain; Patient Care; Patient-Focused Outcomes; Patients; Performance; Peripheral; Pharmaceutical Preparations; Phase; Phenotype; Prevalence; Primary Care Physician; Process; Public Health; RNA; RNA Degradation; Research; Saliva; Salivary; Sampling; Screening procedure; Sensitivity and Specificity; Small Business Technology Transfer Research; Social Interaction; Socialization; Societies; Specialist; Specificity; Stimulus; Symptoms; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Toddler; Training; United States; Untranslated RNA; Validation; Work; accurate diagnosis; autism diagnostic observation schedule; autism spectrum disorder; autistic children; biomarker identification; brain tissue; clinical practice; cohort; combinatorial; commercialization; diagnostic accuracy; diagnostic biomarker; differential expression; endophenotype; exosome; extracellular; functional outcomes; improved; insight; interest; magnetic resonance imaging/electroencephalography; microbial community; microbiota; microvesicles; minimally invasive; multiple omics; neurodevelopment; next generation sequencing; peer; phase 1 study; phase 2 study; primary outcome; prognostic; programs; prospective; response; secondary outcome; standard of care; symptom management; tool; trait; treatment response; visual tracking

Autism spectrum disorder (ASD) is a continuum of neurodevelopmental characteristics that includes deficits in communication and social interaction, as well as restrictive, repetitive interests and behaviors. ASD is an increasing public health concern, with about 1 in 45 American children diagnosed with ASD in 2014, a 10-fold increase in prevalence over the past 40 years. The effect of ASD on both society and the economy is a large burden, estimated at more than $286 billion per year in the U.S. alone. While a single direct link to ASD diagnosis has not been determined, studies have identified genetic, epigenetic, neurological, hormonal, and environmental factors that affect outcomes for patients with ASD. In order to effectively treat patients with ASD, timely detection is crucial for implementation of early treatment options. Using knowledge of these preexisting factors for ASD, doctors can begin treatment while the patient is still young, even if the child has not begun to exhibit typical ASD symptoms. Studies suggest that earlier treatment results in better functional outcomes and reductions in symptoms of ASD. These models, medications and programs have proven to be effective in managing the symptoms of ASD, and may remove some patients from the ASD spectrum entirely. Unfortunately, current diagnostic methods for ASD are not very accurate for young children; the average age of diagnosing ASD is three years old, and about half of those are false positives. Development of accurate diagnostic biomarkers for ASD would thus represent a valuable addition to patient care. Quadrant Biosciences is developing an approach to diagnose ASD by measuring brain-related and other ribonucleic acids (micro, circular, and bacterial) in saliva. Extracellular transport of miRNA via exosomes and other microvesicles is an established epigenetic mechanism for cells to alter gene expression in nearby cells. This has enabled Quadrant to measure genetic material that may have originated from the central nervous system simply by collecting saliva. This method minimizes many of the limitations associated with analysis of post-mortem brain tissue (e.g., anoxic brain injury, RNA degradation, post-mortem interval, agonal state), or peripheral leukocytes (relevance of expression changes, painful blood draws) employed in previous studies. Alterations in the human microbiome (i.e., microbial communities) have also been shown to correlate with ASD. Thus, extracellular RNA quantification in saliva provides an attractive and minimally invasive technique for biomarker identification in children with ASD. This Phase II study will test the hypothesis that a pre-defined panel of human and non- human RNAs will accurately determine ASD status in a cohort of 1600 children ages 18 months to 6 years. Using prospective clinical trial methodology, with input from FDA, the project will provide data essential to the commercialization of Quadrant’s ASD diagnostic technology, further testing the algorithm with the inclusion of additional children and following children who are flagged with the currently utilized ASD to determine their ultimate diagnosis.

自闭症谱系障碍（ASD）是一个连续的神经发育特征，包括在

项目成果

Evidence-based use of scalable biomarkers to increase diagnostic efficiency and decrease the lifetime costs of autism.

• DOI: 10.1002/aur.2498
• 发表时间: 2021-06
• 期刊: Autism research : official journal of the International Society for Autism Research
• 作者: Frazier TW;Coury DL;Sohl K;Wagner KE;Uhlig R;Hicks SD;Middleton FA
• 通讯作者: Middleton FA

Longitudinal stability of salivary microRNA biomarkers in children and adolescents with autism spectrum disorder.

• DOI: 10.1016/j.rasd.2021.101788
• 发表时间: 2021-07
• 期刊: Research in autism spectrum disorders
• 影响因子: 2.5
• 作者: David Levitskiy;A. Confair;Kayla E Wagner;Samantha DeVita;N. Shea;E. McKernan;J. Kopec;N. Russo;F. Middleton;S. Hicks

A Comparative Review of microRNA Expression Patterns in Autism Spectrum Disorder.

• DOI: 10.3389/fpsyt.2016.00176
• 发表时间: 2016
• 期刊: Frontiers in psychiatry
• 影响因子: 4.7
• 作者: Hicks SD;Middleton FA
• 通讯作者: Middleton FA

Saliva RNA Biomarkers of Gastrointestinal Dysfunction in Children With Autism and Neurodevelopmental Disorders: Potential Implications for Precision Medicine.

• DOI: 10.3389/fpsyt.2021.824933
• 发表时间: 2021
• 期刊: Frontiers in psychiatry
• 影响因子: 4.7
• 作者: Beversdorf DQ;Sohl K;Levitskiy D;Tennant P;Goin-Kochel RP;Shaffer RC;Confair A;Middleton FA;Hicks SD
• 通讯作者: Hicks SD