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Serum Raman spectroscopy as a diagnostic tool in patients with Huntington's disease
Anna Huefner1,2, Wei-Li Kuan2, Sarah L Mason2
1Department of Chemistry , University of Cambridge , Lensfield Road , Cambridge , CB2 1WE , UK.
Insights
Researchers used Raman spectroscopy techniques to analyze serum from Huntington's disease (HD) patients. Surface-enhanced Raman spectroscopy (SERS) identified spectral biomarkers correlating with disease progression, offering potential for patient stratification and monitoring.
Area of Science:
- Neurodegenerative disease research
- Biomarker discovery
- Spectroscopic analysis
Background:
- Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder.
- Caused by CAG expansion in the huntingtin (HTT) gene.
- Current disease progression tracking lacks objective biomarkers.
Purpose of the Study:
- To explore spectral profiles of serum from HD patients and healthy individuals.
- To identify potential spectral biomarkers for HD progression using Raman spectroscopy (RS) and surface-enhanced Raman spectroscopy (SERS).
- To assess the utility of SERS and RS for patient stratification and disease monitoring.
Main Methods:
- Collected serum samples from healthy participants and HD patients across various disease stages.
- Utilized surface-enhanced Raman spectroscopy (SERS) and Raman spectroscopy (RS) to generate spectral profiles.
- Analyzed spectral data for genotype- and gender-specific segregation and correlations with disease progression.
Main Results:
- Both SERS and RS showed genotype- and gender-specific segregation in the spectral fingerprint region.
- SERS identified significant correlations between spectral intervals and HD progression.
- Serum molecules related to protein misfolding and nucleotide catabolism were associated with disease progression from pre-manifest to advanced HD.
Conclusions:
- Raman spectroscopy-based techniques show potential for stratifying HD patients.
- SERS can provide spectral biomarkers to track disease status in Huntington's disease.
- Findings suggest potential clinical applications for other diseases and therapeutic trials.
Abstract:
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an abnormal CAG expansion in exon 1 of the huntingtin (HTT) gene. Given its genetic basis it is possible to study patients both in the pre-manifest and manifest stages of the condition. While disease onset can be modelled using CAG repeat size, there are no easily accessible biomarkers that can objectively track disease progression. Here, we employed a holistic approach using spectral profiles generated using both surface-enhanced Raman spectroscopy (SERS) and Raman Spectroscopy (RS), on the serum of healthy participants and HD patients covering a wide spectrum of disease stages. We found that there was both genotype- and gender-specific segregation on using the full range in the fingerprint region with both SERS and RS. On a more detailed interrogation using specific spectral intervals, SERS revealed significant correlations with disease progression, in particular progression from pre-manifest through to advanced HD was associated with serum molecules related to protein misfolding and nucleotide catabolism. Thus, this study shows the potential of Raman spectroscopy-based techniques for stratification of patients and, of SERS, in particular, to track disease status through provision of 'spectral' biomarkers in HD, with clinical applications for other diseases and trials looking at disease modifying therapies.
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