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Seed Amplification Immunoassay (SAIA) for Synucleinopathies

Abstract

Synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are characterized by the accumulation of α-synuclein aggregates. Early and accurate diagnosis remains a critical challenge in managing these disorders. The Seed Amplification Immunoassay (SAIA) is a highly sensitive and specific diagnostic platform capable of detecting α-synuclein aggregates at attogram levels in various biofluids and tissue samples.

Our work on the SAIA highlights its remarkable utility in diagnosing synucleinopathies across diverse clinical and research applications. By leveraging its exceptional specificity, SAIA reliably differentiates synucleinopathies such as Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy from other neurodegenerative conditions.

The assay’s high sensitivity enables the detection of α-synuclein aggregates at early stages of disease progression in cerebrospinal fluid and tissue samples, including brain and skin homogenates. Its application in prodromal cases, such as REM sleep behavior disorder (RBD), underscores its potential for identifying disease before the onset of motor symptoms. Furthermore, SAIA’s adaptability to skin biopsies expands its diagnostic versatility, offering a minimally invasive option for clinical settings.

These findings establish SAIA as a transformative tool for the early diagnosis and monitoring of synucleinopathies, paving the way for timely interventions and personalized therapeutic strategies to improve patient outcomes.

Key Performance Indicators

91.5%

Sensitivity

90.2%

Specificity

0.96

AUC

Conclusion

The SAIA assay represents a significant advancement in the diagnosis of synucleinopathies:

  • High sensitivity and specificity for α-syn aggregates
  • Early detection of trace amounts of aggregates in prodromal cases, supporting early diagnosis and timely intervention.
  • Clear differentiation between synucleinopathies and other neurodegenerative disorders.
  • Potential for monitoring disease progression and treatment efficacy in clinical trials.

These features position SAIA as a powerful tool in the fight against neurodegenerative diseases, offering new hope for early intervention and improved patient outcomes.

Our Development Pipeline

Plasma-Based SAIA Assay Development

Current Stage

Adaptation and validation of the Seed Amplification Immunoassay (SAIA) for use in plasma samples.

Next Steps

  • Complete optimization of plasma-based assay sensitivity and specificity.
  • Conduct validation studies in patient cohorts to ensure clinical utility.

Goal

Launch the plasma-based SAIA assay as a non-invasive, accessible diagnostic tool for early detection and differentiation of synucleinopathies.

Development of Novel Blood Assays

Current Stage

QABY is in the advanced stages of developing three innovative ELISA tests utilizing proprietary antibodies. These assays have shown promising preliminary results in detecting biomarkers in biological samples, such as blood, from patients with PD, DLB, and MSA. However, further validation and optimization are ongoing to ensure robustness and reliability.

Next Steps

  • Conduct comprehensive analytical and clinical validation of the ELISA tests.
  • Investigate scalability and adaptability for widespread clinical use.

Goal

Develop a reliable suite of blood-based diagnostic tools that provide accurate and minimally invasive options for detecting synucleinopathies, enhancing diagnostic capabilities for clinical and research applications.

Preclinical Development of Nanobody Therapeutics

Current Stage

Preclinical studies of nanobody therapies targeting alpha-synuclein aggregates are ongoing using animal models.

Next Steps

  • Finalize preclinical efficacy and safety testing in animal models.
  • Optimize nanobody formulation for maximum intracellular delivery and stability.

Goal

Transition to Phase 1 clinical trials, focusing on disease-modifying therapies for Parkinson's disease and other synucleinopathies.

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