NetraMark Holdings Inc. announced the presentation of new data demonstrating the ability of its proprietary NetraAI clinical trial solution to untangle the intricate web of factors contributing to PD, offering insights applicable to other neurodegenerative disorders, including AD. Application of NetraAI to a dataset of 588 individuals provided by the Michael J. Fox Foundation identified multiple markers associated with PD pathogenesis, including several that are closely linked to the immune system and immune responses. The data was presented in a poster at AD/PD??

2024, which took place March 5-9 in Lisbon, Portugal. The poster, titled "Using NetraAI to Discover Parkinson's Disease Subtypes: Generative AI Reveals Transcriptomic Personas Linking Mitochondrial, Microbiome, and Immune Signaling," reports the results of an analysis in which NetraAI was used to identify genetic drivers within specific PD patient subpopulations and uncover pivotal disease pathways. A transcriptomic data set assembled from 397 patients with PD and 191 controls was analyzed using NetraMark's AttractorAI algorithms to identify variables (called hypotheses) explaining specific subpopulations within the data set.

Transcriptomic data comprises RNA transcripts and reflects which genes are expressed in each subpopulation. Each Netra-Perspective within this analysis divides the patient population into explainable and unexplainable subsets of patients according to a set of variables and is designed to capture different aspects of complex diseases like PD. Combining different NetraPerspectives provides a holistic view of the patient population, and integration of the various hypotheses reveals significant variables and pathways linked to PD.

Key findings from this analysis include: One Netra-Perspective identified two unexplainable and three explainable subpopulations using defined criteria and the statistical significance of the variables. Within the explainable subpopulations, NetraAI identified an increased number of RNA transcripts for GPATCH2L (which is involved in metabolism of macromolecules), Rbbp (which regulates transcription), and EphA1 (which improves inflammatory responses and neuropathological changes in a model of PD). Evaluation of these genes in a protein-protein interaction network further identified links to two proteins that are closely linked to immune-mediated functions: CLECB1 (which regulates cytotoxicity and cytokine secretion), and IRAK3 (a negative regulatory marker of inflammation).

A different Netra-Perspective strongly implicated the gene BPI (upregulated in PD), which is involved in protecting against gram-negative bacteria. These variables are primarily associated with immune signaling, particularly the innate immune system's response to microbial pathogens, which may involve interactions with the microbiome. Other Netra-Perspectives identified more of a mitochondrial and microbiome role.

These findings lead to the hypothesis that BPI is overexpressed in some PD patients as a protective immune response to gut microbiome abnormalities that impact brain health.