MicroRNAs (miRNAs) are small RNAs that regulate gene expression predominantly by inhibiting translation or promoting degradation of the target RNAs.
Many dysregulated miRNAs are implicated in pathogenesis of various diseases. Such miRNAs have become a new hot topic in drug discovery and diagnostics. Several specific characteristics of miRNAs in combination with compelling therapeutic efficacy data have triggered the exploration of miRNAs as therapeutic entities.
CHI’s “MicroRNA as Biomarkers and Diagnostics,” a conference scheduled to take place next month in Boston, will cover the latest developments in the use of miRNAs in the early detection and monitoring of disease progression, as well as the potential for personalized medicine based on miRNA profiles. Selected presentations from the conference will highlight the translation of miRNA bench discoveries to therapeutically useful modalities.
Parkinson’s disease (PD) is believed to reach a relatively advanced stage by the time it is clinically diagnosed. By then, more than half of patient’s dopaminergic neurons may be lost because of neurodegeneration. Despite unification and standardization of clinical assessments, the accuracy of diagnosis is still subjective.
“Unlike cancer, PD does not afford an opportunity for tissue biopsy. Our best hope is to find presymptomatic, sensitive, and quantifiable biomarkers in body fluids,” says Sok Kean Khoo, Ph.D., distinguished associate professor of molecular genomics at Grand Valley State University. “Such biomarkers would undoubtedly help with early disease diagnosis and potentially stop or slow down disease progression.” A number of blood and cerebrospinal fluid biomarkers have been studied, but none has yielded a biomarker possessing the ideal features.
Dr. Khoo’s team focuses on the modulating role miRNAs may play in PD. In one investigation, the team used microarrays to perform global miRNA expression profiling on blood samples of 32 PD patients with matching controls from Mercy Health Saint Mary’s.
The data was analyzed by integrating two statistical algorithms. One of the algorithms identified 13 miRNAs predominantly overexpressed in PD. Another algorithm identified nine miRNA pairs calculated by statistical probabilities of each miRNA in a pair being present or absent in PD. Each miRNA pair becomes an independent predictor of PD; several such pairs constitute a PD signature.
The miRNAs were further validated using quantitative RT-PCR, narrowing it down to just three individual miRNAs and five miRNA pairs. “We were able to access a validation sample set from Umea University Hospital in Sweden,” recalls Dr. Khoo. “This set contained 30 patients with treated or untreated PD, but also has samples from patients with multiple system atrophy and progressive supranuclear palsy, as well as healthy controls. Initially one miRNA was undetectable, but with a nonbias amplification method, we are now able to replicate all our findings.”
Encouraged by these results, Dr. Khoo together with the Michael J. Fox Foundation will use the miR panel to follow the PD progression. The miRNA signatures may help researchers understand the differences between PD fast and slow progressors. At the same time, Dr. Khoo continues to dive deeper into the biology of the miRNA biomarkers. “We have yet to understand the biological functions of some of the strongest PD predictors in our signature set,” remarks Dr. Khoo.