Mechanism and Therapeutic Prospect of miRNAs in Neurodegenerative Diseases

Table 2

Clinical trials of miRNAs in neurodegenerative diseases.

Study name (study date)	Current state	Study type	Subjects (age)	Purpose	Design	Interventions		Outcome measures	Research results
NCT02253732 (09/2015-03/2018)	Completed	Interventional	MCI AD PD HV (60-85)	Prevention	Open label	Exercise	30	miRNA myokines; Cognitive function; Motoric function	Exercise improved MDS-UPDRS, balance, walking speed, bradykinesia, REE, and glucose metabolism and increased the expression of AMPK and the expression of PRKAA1, MGF, Sirt1, Cox7a1, MyHC2, MyHC7, and other related genes increased [208].
NCT02045056 (05/2014-06/2019)	Completed	Interventional	AD (65-90)	Prevention	Double-blind placebo controlled parallel design	Gemfibrozil placebo	72	A E miRNA-107; Aβ1-40/1-42; FCSRT PAL	Not yet released
NCT03388242 (11/2017-03/2020)	Unknown	Observational	MCI (30-80)	Prevention	Open label	No intervention	120	(1) Fold changes of microRNAs in the blood of patients with MCI over control people. (2) Fold changes of proteins in the blood of patients with MCI over control people	Not yet released
NCT04137926 (03/2020-11/2022)	Recruiting	Interventional	AD HV (50-85)	Diagnostic	Double blind	miRNA battery	360	(1) miRNA battery for diagnostic of MCI due to AD. (2) miRNAs for intervene of MCI due to AD	Not yet released
NCT01819545 (01/2012-11/2015)	Unknown	Observational	AD (60-90)	Diagnostic	Open label	No intervention	300	Plasma and CSF press of miRNA 107 and BACE1 mRNA	(1) The overall classification accuracy of miRNA107 to discriminate between patients with amnestic mild cognitive impairment and healthy controls was 91.9%, with sensitivity of 98.3% and specificity of 82.7% [204]. (2) Alterations in key left brain regions associated with memory, language, and emotion in aMCI that were significantly correlated with plasma expression of miRNA107 and BACE1 mRNA [203]
NCT04120493 (10/2019-1/2021)	Recruiting	Interventional	HD (25-65)	Treatment	Double blind	Intrastriatal rAAV5-miHTT imitation (sham) surgery	26	AE AMT-130 fM; UHDRS Q-Motor; HD-CAB MRI; HADS Neuro-QoL	Not yet released
NCT01992029 (06/2014-10/2015)	Terminated	Observational	Amyotrophic lateral sclerosis ALS (45-70)	Diagnostic	Open label	Clinical evaluation; Muscular biopsy; Lumbar puncture; Blood sampling Neurological assessments; Neuromuscular biopsy and lumbar puncture; Blood sample; Cervical spinal cord and brain MRI	5	miRNA expression	Not yet released
NCT03466723 (02/2019-06/2022)	Completed	Observational	PD (30+)	Diagnostic	Open label	Genetic: biomarker identification in Parkinson’s disease	1000	Identification of novel circulating miRNAs as biomarkers for PD	Not yet released
NCT05055310 (10/2016-11/2019)	Completed	Observational	AD (60-90)	Diagnostic	Open label	Diagnostic test: miRNA test	1000	miRNA diagnosis validation for aMCI	Not yet released
NCT03217396 (11/2017-09/2027)	Recruiting	Observational	MS PD ALS AD (18-65)	Diagnostic	Open label	Procedure: lumbar puncture	300	Concentrations of CSF (neurofilaments, beta-amyloid, tau protein, inflammatory cytokines, and microRNAs)	In a large sample of MS patients that let-7b-5p levels in the cerebrospinal fluid (CSF) were highly correlated with a number of microRNAs implicated in MS, as well as with a variety of inflammation-related protein factors, showing specific expression patterns coherent with let-7b-5p-mediated regulation [209]

Aβ: amyloid-beta; AD: Alzheimer’s disease; MCI: mild cognitive impairment; PD: Parkinson; HV: healthy volunteers; HD: Huntington’s disease; AE: adverse events; FCSRT: free and cued selective reminding test; PAL: paired associate learning; BACE1: beta-site APP cleaving enzyme1; fM: CSF mutant protein; CSF: cerebrospinal fluid; UHDRS: Unified Huntington’s Disease Rating Scale; Q-Motor: quantitative motor; HD-CAB: Huntington’s Disease Cognitive Assessment Battery; MRI: magnetic resonance imaging; HADS: Hospital Anxiety and Depression Scale; MDS-UPDRS: clinical disability score; REE: resting energy expenditure; MGF: mechanogrowth factor.