Team:Hong Kong HKU/Description
What is Huntington's disease?
Huntington’s disease (HD) is an inherited neurodegenerative disorder that results in the death of brain cells. Genetic mutations, namely the trinucleotide repeats in the Huntingtin gene (HTT) located on Chromosome 4, lead to the development of HD [1] . Though the disease is incurable, early diagnosis can help to better relieve symptoms by allowing treatments to start sooner. In the early stages of HD, only subtle changes in personality, cognitive and physical abilities can be identified.
Early Diagnosis of Huntington's disease
Diagnosis of HD (in cases where the parents do not have HD) is usually carried out only after symptoms are identified and the patient approaches the medical professionals. As the early symptoms are generally not severe enough to be recognized as HD symptoms on their own, the treatment is usually delayed. Although commercially available RT-PCR arrays for Huntington’s disease gene targets do exist, they tend to be time-consuming and require a level of lab expertise[2] (Figure 2) According to the interviews conducted with the medical workers using various diagnostics tools, their primary concerns were the accuracy of the test and the ease of use. We hope to allow prompt treatment with our non-invasive and highly accessible diagnostic method.
DNA nanostructures and miRNAs as biomarkers
Compared to its antibody based counterparts, DNA based diagnostic device are more stable and do not require a cold-chain, the maintenance of proteins at cool temperature to avoid degradation[3]. DNA has emerged as a promising material that allows researchers to construct novel designs as its structure could be predicted easily and accurately[4]. Examples of DNA nanostructures include nano-tweezers to detect norovirus and a DNA ‘Nano-Claw’ (Figure 4) to detect membrane markers of cancer cells [5,6]
Figure: Nano-Claw
DNA Boolean logic gates have been constructed to produce signals in the presence of multiple targets, such as OR-gate and AND-gate DNA tetrahedra that generate fluorescence resonance energy transfer (FRET) signal when multiple inputs hybridize with the probe[7].
Figure: Protein hybridization process.
As for the targets to be detected, different microRNAs (miRNAs) have been identified to be associated with cancers. For example, miR-15b-5p, miR-338-5p, and miR-764 found in plasma are potential biomarkers for detecting hepatocellular carcinoma cancer (HCC), a common type of liver cancer[8]. It has already been reported that it is promising to use these biomarkers - miRNAs to detect cancers[9].
Figure: Plasma levels of miR-15b-5p, miR-338-5p, and miR-764
For Huntington’s disease, Hsa-miR-34b can be used as a biomarker. This miRNA is stable in the plasma, allowing diagnosis to be carried out just by extracting small amounts of the patient’s blood. The miRNA is also elevated in pre-manifest Huntington’s Disease, which allows HD to be detected at the earliest stage possible, before the surfacing of symptoms[10].
