BIOTECH HORIZONS No.2

Does analyzing your tears give you hints about your diseases?

A recent study published in the Journal of Movement Disorders has uncovered a game-changing insight: mutant huntingtin protein (mHTT)—the pathological hallmark of Huntington’s disease—can be detected in tear fluid using ultra-sensitive bioanalytical technologies.

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#HuntingtonsDisease #Neurodegeneration #Biomarkers #TearFluidDiagnostics #NonInvasiveDiagnostics #PrecisionMedicine #Bioanalytics #SingleMoleculeCounting #Simoa #ClinicalTrials #TranslationalResearch #GLP #GCP #RareDiseases #DigitalHealth #NeuroscienceInnovation #FemtoSensitivity #MolecularDiagnostics #PersonalizedMedicine #Imperacer #MSD

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Tears as a Biomarker Source: New Perspectives for Non-Invasive Diagnostics of Neurodegenerative Diseases

Does analyzing your tears give you hints about your diseases?

A Molecular Breakthrough With Clinical Potential

The search for sensitive, non-invasive biomarkers for neurodegenerative diseases has made remarkable progress: A recent study demonstrates that mutant huntingtin protein (mHTT)—the pathological driver of Huntington’s disease—can be detected in tear fluid. The findings, published in the Journal of Movement Disorders, open new avenues for early diagnosis and disease monitoring.

Tears as a Diagnostic Window Into the CNS

The study analyzed tear samples from 20 symptomatic and 13 pre-symptomatic Huntington’s mutation carriers, as well as 20 healthy controls. Using the ultra-sensitive SMCxPRO technology, significantly elevated mHTT concentrations were detected in mutation carriers—with average levels of 67,223 fM (symptomatic) and 55,561 fM (pre-symptomatic), compared to just 1,622 fM in controls.

The correlation with clinical parameters such as CAG repeat length, estimated time to diagnosis, and Unified Huntington’s Disease Rating Scale (UHDRS) scores underscores the diagnostic relevance. Particularly noteworthy: mHTT levels in tears showed high diagnostic accuracy, with AUC values of 0.975 (symptomatic vs. control) and 0.985 (pre-symptomatic vs. control).

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Bioanalytical Implications for Drug Development

These findings are significant not only for basic research but also for the preclinical and clinical development of therapeutics. The ability to quantify pathological proteins in minimally invasive matrices like tear fluid opens new possibilities for longitudinal monitoring, patient selection, and therapy response analysis—especially in rare diseases with limited sample availability.

However, implementing these analyses requires highly sensitive platforms capable of delivering valid results even at extremely low concentrations (in the femtomolar range). Technologies such as Single Molecule Counting (SMC), Simoa®, MSD™, or immuno-PCR (e.g., Imperacer®) are essential. Their ability to generate robust data from minimal sample volumes makes them indispensable tools in modern bioanalytics.

Regulatory Requirements and Assay Validation

For the translational application of such biomarkers—whether in clinical trials or drug approval processes—validation according to GLP/GCP standards is essential. Developing customized assays, validating them fit-for-purpose, and transferring them into regulated environments places high demands on bioanalytical partners. Only precise, reproducible data can overcome regulatory hurdles and support sound clinical decision-making.

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Future Outlook: From Tear to Treatment Decision

The detection of mHTT in tear fluid is more than a scientific milestone—it is proof that innovative bioanalytics can unlock new diagnostic horizons. In an environment where time, sensitivity, and regulatory compliance are critical, the ability to reliably analyze even rare matrices becomes a strategic advantage.

Integrating such biomarkers into clinical trials—as surrogate endpoints or for patient selection could accelerate the development of huntingtin-lowering therapies and enable personalized treatment strategies. This requires close integration of scientific expertise, technological excellence, and regulatory experience.

Source:
Titel: High Levels of Mutant Huntingtin Protein in Tear Fluid From Huntington’s Disease Gene Expansion Carriers Authors: Marlies Gijs et al. Reference: Journal of Movement Disorders, 2024;17(2):181–188 DOI: 10.14802/jmd.24014 Link: High Levels of Mutant Huntingtin Protein in Tear Fluid From Huntington’s Disease Gene Expansion Carriers