The Need HD is a dominantly inherited neurodegenerative disorder caused by a mutant Huntington gene Diagnosis of HD is determined by genetic testing but clinical stage and age of onset must be defined by its symptoms Diverse disease landmarks precede the onset and define the premanifest stage P ID: 1045179
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1. METHOD FOR THE DIAGNOSIS OR PROGNOSIS OF HUNTINGTON DISEASEThe NeedHD is a dominantly inherited neurodegenerative disorder caused by a mutant Huntington gene. Diagnosis of HD is determined by genetic testing but clinical stage and age of onset must be defined by its symptoms. Diverse disease landmarks precede the onset and define the premanifest stage (P-HD). The plasma neurofilament light chain (NfL) has high prognostic value but it is not disease specific. Small RNAs (sRNAs) may have a role in HD pathogenesis, being responsible for transcriptomic deregulation occurring during the disease. Understanding sRNA expression dynamics should provide clues about its role in P-HD and about the progression of the disease.The SolutionWe have patented P-HD specific biomarkers sensitive enough to stratify patients and/or to monitor changes prior to clinical decision.The extracellular sRNAs transcriptome from plasma was explored in healthy volunteers’ samples and in HD patients, for the last, either using an enriched plasma subfraction of extracellular vesicles or not.The inventors observed that most extracellular sRNAs are downregulated in HD and that early deregulation of specific extracellular sRNAs correlate with premanifest alterations. They have identified specific extracellular sRNAs with great diagnostic accuracy at premanifest stages.Innovative AspectsEight RNA sequences have been analysed both individually and in combination, showing statistical value to discriminate between P-HD and control samples.Best statistical results achieved were of AUC 0,943 and p-value 0,0001 for the combination of the biomarkers with NfL.The sequences showing higher relevant results both individually or in combination with other biomarkers are tRNAs fragments that comprises the 5’ end of tRNAGlu/CTC and tRNAGly/GCC The in vitro method involves assessing the level of expression of a tRNA fragment that comprises the 5’ end of tRNAGlu/CTC and tRNAGly/GCC or the use of a tRNAGlu/CTC and tRNAGly/GCC or of a kit comprising reagents for the detection of these tRNAs. After processing the expression level values, a risk score is obtained, which when differing from the reference value is an indicative that the subject is suffering from HD or has a poor prognosis. Stage of Development: TRL 3. Proof of concept.Intellectual Property:Spanish patent application filed (February, 23rd 2023) Contact detailsA research group from CIBER, Universitat de Barcelona and Fundació Institut de Recerca de l’Hospital de la Santa Creu I Sant Pau has developed an in vitro method for the diagnosis or prognosis of Huntington’s disease (HD) preferably for the early diagnosis or prognosis of HD.Centro de Investigación Biomédica en Red (CIBER)isabel.perez@ciberisciii.esotc@ciberisciii.eshttps://www.ciberisciii.es/enAimsLooking for a partner interested in a license and/or a collaboration agreement to develop and exploit this asset.Technology OfferVenn Diagram of differentially expressed sRNAs-clusters between P-HD vs control (CTL) and M-HD vs CTL, showing the number of overlapped dysregulated sRNAs-clusters between both comparisons.Schematic representation of the workflow followed in EV fraction and Non-EV fraction isolated from P-HD, MHD and control (CTL) plasma.