NEW YORK (GenomeWeb) – A study of participants from the University of Iowa-led PREDICT-HD prospective observational study suggests a handful of microRNAs are found at enhanced levels in cerebrospinal fluid (CSF) samples from individuals who go on to develop Huntington disease (HD).
As they reported in Neurology last week, the researchers profiled miRNA levels in CSF from 30 not-yet-diagnosed individuals carrying the type of huntingtin gene expansions linked to the neurodegenerative condition. By looking at levels of more than 2,000 miRNAs patterns and comparing them with those in CSF samples from 15 individuals previously diagnosed with HD and 15 unaffected controls, they searched for telltale miRNAs with ties to eventual HD development.
In particular, the team noted that half a dozen miRNAs appeared to be present at higher-than-usual levels in CSF samples from those with preclinical HD, known as the prodromal stage of disease. Those miRNAs — miR-520f-3p, miR-135b-3p, miR-4317, miR-3928-5p, miR-8082, and miR-140-5p — appeared to ramp up with increasing HD risk, the group noted, suggesting they may warrant follow up as potential biomarkers for HD prior to symptom development.
"Importantly, miRNAs were detected in the prodromal HD groups furthest from diagnosis where treatments are likely to be most consequential and meaningful," corresponding author Richard Myers, a neurology researcher and director of Boston University's Genome Science Institute, and his colleagues wrote.
The team turned to HTG Molecular Diagnostics' HTG EdgeSeq approach to assess miRNA levels in CSF from 30 prodromal individuals, 15 established HD cases, and 15 healthy controls, focusing on differential expression at 2,081 miRNA probes in the 56 samples that met the group's quality control criteria.
From the 25 miRNAs that appeared to have enhanced CSF levels in the prodromal HD cases, the researchers whittled the set down to six miRNAs significantly associated with disease development. And in their subsequent analyses of miRNAs alongside HD risk levels, they noted that CSF representation of the miRNAs notched up with rising HD risk.
Though the authors cautioned that "the sample size of 60 studied here may not have sufficient power to detect all of the miRNAs that are altered in diagnosed or prodromal HD relative to controls," they noted that it may be possible to tap the miRNA set for CSF-based markers of HD to inform future trials focused on finding new HD treatments.
"[T]he levels of the microRNAs begin to increase many years before the individual shows symptoms and continue to increase as disease onset approaches," Myers said in a statement. "Clinical trials for new HD treatments that may reduce the levels of the microRNAs suggest that these treatments may postpone the onset of the disease."