Mr. Swapan Kakumanu reports

NETRAMARK'S AI-BASED CLINICAL SOLUTION IDENTIFIES PARKINSON'S DISEASE SUBTYPES LINKED BY MITOCHONDRIAL, MICROBIOME AND IMMUNE SIGNALING

Netramark Holdings Inc. has presented 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 to 9 in Lisbon, Portugal.

"The results of this analysis not only advance our understanding of PD but also offer a scientific foundation for future investigations into the role of immune-related factors in neurodegenerative disorders. They also provide new opportunities for improving clinical trials through patient enrichment," said Dr. Joseph Geraci, PhD, founder and chief scientific officer of Netramark. "Our unique approach opens new avenues for the diagnosis and treatment of PD and has tremendous potential to accelerate development of urgently needed therapies for PD and other debilitating neurological conditions."

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 dataset 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 dataset. Transcriptomic data comprises RNA transcripts and reflects which genes are expressed in each subpopulation.

Each NetraPerspective 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 NetraPerspective 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 NetraPerspective 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 NetraPerspectives 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.

"These findings add to the growing body of data demonstrating the power of the AttractorAI technologies on which NetraAI is based to identify the variables and provide hypotheses that explain specific patient subpopulations, even in highly complex neurological and psychiatric diseases," added Dr. Geraci.

In February, 2024, Netramark reported data at the International Society for CNS Clinical Trials and Methodology (ISCTM) 20th annual meeting demonstrating the potential of NetraAI to enable more efficient clinical development of therapies to treat a variety of mental health disorders, including bipolar disorder, anxiety and schizophrenia.

About Netramark Holdings Inc.

Netramark is a company focused on being a leader in the development of generative artificial intelligence/machine learning (ML) solutions targeted at the pharmaceutical industry. Its product offering uses a novel topology-based algorithm that has the ability to parse patient datasets into subsets of people that are strongly related according to several variables simultaneously. This allows Netramark to use a variety of ML methods, depending on the character and size of the data, to transform the data into powerfully intelligent data that activates traditional AI/ML methods. The result is that Netramark can work with much smaller datasets and accurately segment diseases into different types, as well as accurately classify patients for sensitivity to drugs and/or efficacy of treatment.

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