Exploring Beyond: Kari Wong Sheds Light on Metabolon's Strategic Collaboration with SITraN

Shots:

Following the strategic collaboration with the Sheffield Institute for Translational Neuroscience (SITraN), Metabolon’s scientific strategic director Kari Wong, engages in an illuminating conversation with PharmaShots
The collaboration aims to enhance the understanding of ALS and motor neuron disease (MND) by integrating a comprehensive biomarker approach to provide better diagnostics and therapeutics for these challenging conditions
While highlighting Metabolon’s expertise in contributing to the advanced research of ALS, Kari talks about other collaborations that are aimed at expanding Metabolon’s portfolio of neurological diseases

Saurabh: Congratulations on the partnership with the Sheffield Institute for Translational Neuroscience (SITraN) and A Multicentre Biomarker Resource Strategy in ALS (AMBRoSIA). Please brief us about this strategic collaboration. 

Kari: Thank you, we are very excited to launch this new partnership with SITraN and the AMBRoSIA cohort. This partnership will undoubtedly provide insights into ALS pathology. Motor neuron diseases (MND), which include ALS, are a devasting group of diseases with limited therapeutic options. By combining Dame Pamela Shaw’s experience in the genetic underpinnings of ALS and Metabolon’s expertise in metabolomics, our goal is to understand the gene-environment interactions that shape disease status. The primary objective of this initial project is to profile the plasma and cerebrospinal fluid (CSF) of 100 patients at the baseline. These individuals have undergone genetic profiling and have been thoroughly characterized clinically. Furthermore, we have the opportunity to compare their data with that of non-affected controls. This study design enables us to delve into the metabolic profiles within the framework of the patients' genes and clinical presentation. The integration of these diverse data streams facilitates a comprehensive approach to the analysis. As the AMBRoSIA cohort is set up for longitudinal collections, we hope that this is the first step in a longer partnership to explore the metabolome of ALS patients.

Saurabh: Tell us about the objectives that you have in mind to achieve with this collaboration.

Kari: The progression of ALS is a step-wise process that likely involves both genetic and environmental cues. In this cohort of patients, genetics alone provided clinically actionable insights in ~21% of the patients. By layering metabolomic data on top of the current genomic data, we hope to increase this number. While the majority of ALS cases are considered sporadic, there is evidence that variants of unknown significance (VUS) also influence the disease. In addition to providing tools based on currently available treatments, we hope to explore the functional impact of these VUSs.

Saurabh: Metabolon mentioned a comprehensive biomarker approach., would you like to tell our readers about this comprehensive biomarker approach? 

Kari: We will be profiling these samples using Metabolon’s Global Discovery Platform.  Our platform can detect and measure an extremely diverse set of small molecules across multiple nodes of biology. This unbiased approach allows us to avoid preconceived notions about ALS facilitating the identification of novel ALS biomarkers.  Our Global Discovery Platform detects metabolites across all major superpathways, including amino acids, peptides, carbohydrates, energy, lipids, vitamins and cofactors, nucleotides, and xenobiotics. Our library of over 5,400 metabolites consists of endogenous metabolites, those that are generated by the patient, as well as exogenous metabolites, those that are derived from the environment (i.e. diet, microbiome).

Saurabh: How do you think this comprehensive biomarker approach will contribute to the understanding of ALS and Motor neuron diseases (MND)? 

Kari: ALS is a complex disease that is the result of both genetic and non-genetic influences, which makes it challenging to develop effective treatments. Metabolic profiling enables us to observe the combined effects of these influencers. By understanding how the environment and genes interact, we will be able to stratify patient populations to better understand the disease pathogenesis. As the functional readout of genes, the metabolic profile may also link genes to specific pathways that may be developed as therapeutic targets.

Saurabh: How does Metabolon's expertise in metabolomics contribute to advancing ALS research at the Sheffield Institute for Translational Neuroscience? 

Kari: Metabolon has over 20 years of experience in measuring and interpreting metabolomics studies. We understand how these small molecules are connected and their relationships, which facilitates the distilling of complex data into understandable and actionable insights. Over the last 20 years, our data has been used to understand a spectrum of disease pathologies. For example, metabolomics was integral in elucidating how a genetic variant in the SLCO1B1 influenced blood pressure and therefore cardiovascular health. By building on the tools for multi-omic integration, we will be able to apply these tactics to this collaboration.

Saurabh: According to you, what could be the possible challenges to be addressed with this approach?

Kari: ALS is a heterogenous disease which makes identifying a panacea for all patients challenging. Metabolomics will be helpful in disentangling the metabolic perturbations observed in these patients, potentially stratifying the patient population by identifying ALS metabotypes. These metabotypes may be used in directing clinical care as well as developing personalized strategies to treat ALS patients. The challenge will be to validate these findings in additional ALS cohorts. The data from this initial project will lay the groundwork for future studies in this area.

Saurabh: You talked about neurological disease. Are there other therapy areas in your portfolio that you focus on?

Kari: In recent years, Metabolon has been expanding its portfolio to focus on neurodegenerative diseases. This involves collaborating with various cohorts such as BioFinder2 for Alzheimer's, and ProBand and Oxford PD for Parkinson's Disease. All these diseases share a common characteristic: the influence of gene-environment interactions. As mentioned earlier, metabolomics plays a crucial role in uncovering the pathways that connect these disease influencers.

The literature is filled with unvalidated signatures linking metabolic patterns to neurological diseases, hindered by variations in methods and approaches. By bringing these cohorts together on Metabolon's high-quality platform, we can comprehensively approach neurological diseases, examining both shared and unique pathways. This approach enables the creation of a comprehensive atlas connecting neurological diseases, metabolomics, and clinical presentation. 

Image Source: Canva

About the Author:

Kari Wong

Dr. Kari Wong is a Scientific Strategy Director and has been at Metabolon for almost eight years.  She currently develops partnerships and scientific strategies that support sustained company growth by working with collaborators to understand how metabolomics can be integrated into research and development pipelines.  Previously, she headed the Population Health group, working with large cohorts from around the world.  Dr. Wong has also collaborated with industry stakeholders to understand the application of metabolomics in their drug discovery and development strategies.

Prior to Metabolon, Dr. Wong served as a research scientist and postdoctoral fellow at the Duke Molecular Physiology Institute where she began working with metabolomics datasets.  Her research focused on the importance of fuel utilization pathways in pre-clinical models of diet and exercise-induced weight change. In her 10+ years as a biochemist working with metabolomics datasets, she has presented at international meetings as well as contributed to numerous publications and poster presentations.