Method for diagnosing Hereditary Hemorrhagic Telangiectasia (HHT)

HHT is a rare disease (estimated prevalence is 1-5/10.000) with autosomal dominant inheritance that results in arteriovenous dilatations in skin, mucous membranes and internal organs, with propensity to hemorrhagic episodes.

The current diagnosis is clinical, but the diagnosis is often delayed due to the gradual onset of symptom. Thus, having a clinical suspicion, the confirmation test available is a mutational genetic analysis. However, the mutational study in the target genes described so far also fails to diagnose all patients (predominance of new mutations in affected individuals and difficulties in the detection of mutations in heterozygosis and in non-coding regions of DNA).

Given this problem, the present invention provides the use of new diagnostic biomarkers, based on the quantification of 8 microRNAs carried by plasma exosomes. These miRNAs provide useful data for the diagnosis of HHT and allow us to classify the disease in two subtypes: HHT1 and HHT2.

Another object of this invention is a kit to assess the expression level of miRNAs through different molecular biology techniques.

ADVANTAGES AND BENEFITS

• Early diagnosis.The current diagnosis of HHT depends on the onset of the symptoms. This new method would allow an early diagnosis, providing a better quality of life for patients and a reduction of healthcare costs.
• Diagnosis independent of genetic mutations.This approach solves the inconvenience of diagnosing a small percentage of patients who do not carry the mutations in the candidate target genes.
• It allows us to classify the disease in two variants, HHT1 and HHT2.
• Suitability of the biological sample analyzed:
  • The biological sample analyzed is easily accessible: liquid biopsy (blood extraction).
  • Plasma exosomes have a high bioavailability and are relatively easy to obtain.
• Simple and efficient analysis of disease.
  • The fact that the present invention uses miRNAs (very short and well-defined RNAs) as diagnostic biomarkers has the advantage of allowing an easy and reliable detection; unlike the current genetic test, which requires the complete sequencing of several genes.
  • Furthermore, the present invention uses optimized probes for miRNAs, thus increasing the limit of detection and specificity.
• The necessary equipment is common and accessible in regular laboratories.One of the possible ways to quantify the expression of miRNAs uses real-time PCR (qPCR). This technique is very popular nowadays and has evolved enormously, and its costs, consequently, have been significantly reduced, especially in the required instruments.

Current development status

Experimental technologies

Applications

Diagnosis

Desired business relationship

Patent licensing

Technology development

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Attachment CC: Herbert L. Fred, MD and Hendrik A. van Dijk [Attribution]