BDNF as a Biomarker for Spinocerebellar Ataxia

Spinocerebellar ataxia (SCA) is a devastating neurodegenerative disease characterized by cerebellar and spinal cord degeneration. It affects approximately 1 to 5 individuals per 100,000 worldwide.¹ Around 50 different subtypes of SCA have been identified,² with spinocerebellar ataxia Type 1 (SCA1) being one of the most common.

While these subtypes are distinct, they often share clinical attributes. Notably, there has been significant progress in understanding the disease biology of SCA1.³ This knowledge not only sheds light on SCA1 but also provides insights into potential biomarkers and disease mechanisms relevant to other SCA subtypes.

The identification of biomarkers is crucial in SCA research. Biomarkers provide key insights into the state and progression of a disease, in addition to patient response to treatments. As such, biomarkers can improve the success rates of drug development, accelerating the availability of new therapeutics. Here we present a use case to identify potential biomarkers of SCA1 using Causaly.

Causaly can machine-read the literature to extract a list of potential biomarkers of SCA1, uncovering ataxin-1 as the most studied. Mutations in the ATXN1 gene (which encodes for ataxin-1) are strongly implicated in SCA1 pathology, affecting key functions including gene expression and signal transduction.⁴ Recent studies reported that disruption in ATXN1-related protein-protein or protein-DNA interactions play a key role in the development and progression of this disease.⁵

Over 400 biomarkers in preclinical models were identified. Delving deeper into those reported since 2022 revealed around 70 specific biomarkers for SCA1. Among the presented biomarkers, brain-derived neurotrophic factor (BDNF) was identified as an emerging biomarker for SCA1 studied in preclinical models.

BDNF is a protein that plays a vital role in the growth and survival of neurons in the brain. Crucially, this protein participates in neuronal plasticity – a function essential for learning and memory⁶ – and has been implicated in major brain disorders included Alzheimer’s and Parkinson’s diseases.⁷

Leveraging Causaly, a downregulated relationship between SCA1 and BDNF was identified. A 2023 study reported lower levels of BDNF were associated with early SCA1 pathology in different regions of the brain, namely the hippocampus and cerebellum.⁸ Complementary to this, a study reported that post-symptomatic delivery of extrinsic human BDNF improved SCA1 pathogenesis in a transgenic mouse model of SCA.⁹

In this Causaly use case, we identified BDNF as a potential biomarker of interest for SCA1. These findings emphasize the potential of BDNF protein in developing effective SCA1 treatments, affirming its value in neurodegenerative disease research.

To find out more about how you can use Causaly to accelerate your research, request a demo here!