Shots:

• Karl spoke on Metabolon’s partnership with the University of Oxford Parkinson’s Disease Centre (OPDC) to identify new metabolomic biomarkers for the advancement of Parkinson’s research 
• Karl also talked about the metabolomic changes which occur in Parkinson’s disease and how Metabolon will support OPDC's mission to improve research and understanding of the biology of early Parkinson's to manage its proactive symptoms
• The interview focuses on how metabolomics is emerging as a tool for biomarker identification of various diseases

Smriti: Put some light on your partnership with the University of Oxford Parkinson’s Disease Centre (OPDC)

Karl Bradshaw: What attracted us to the Oxford Parkinson’s Disease Centre (OPDC) is the quality of the biological samples and the associated data that has been collected from their patients. The OPDC is a leading Parkinson’s disease cohort and among the most deeply phenotyped and genotyped Parkinson’s cohorts in the world. This combined with the longitudinal sampling of patients across both blood and cerebrospinal fluid (CSF) will enable Metabolon and Oxford to gain insights into the metabolomic changes occurring during Parkinson’s disease progression over many years and could reveal new findings to help patients with this devastating disease.

Smriti: Discuss the specifications of the metabolomic changes that occur during the progression of Parkinson’s disease.

Karl Bradshaw: Parkinson’s disease is multi-faceted, encompassing a myriad of biological processes (inflammation, oxidative stress, mitochondrial dysfunction), and global metabolomic profiling offers the opportunity to systematically survey these processes in a single sample. Metabolomics can be applied to a variety of matrices including CSF and plasma.  CSF is of particular interest due to its proximity to the disease source.  For example, dopamine and its associated metabolites have been shown to be altered in Parkinson’s patients.  Blood-based metabolomics has also demonstrated differing metabolomic profiles between Parkinson’s and non-Parkinson’s disease patients, including differences in tryptophan metabolites. More recently, the relationship between gut microbiota and Parkinson’s disease has come to light. Metabolomic profiling offers the opportunity to identify the functional output of microbial activity and understand how this influences disease etiology, an under-explored, but exciting and extremely promising area of Parkinson’s disease research.

Smriti: How will this collaboration with The Oxford Parkinson's Disease Centre (OPDC) help you to detect new therapeutic targets?

Karl Bradshaw: Metabolomics measures metabolites, the small-molecule end-products in biological systems. Our biochemical composition, the type, and the quantity of small-molecule metabolites circulating in our bodies are central to our phenotype, offering a snapshot of our current state of health. Many factors, including genes, diet, lifestyle, environment, and the microbiome, exert their influence by subtly changing our biochemical composition, known as the metabolome. Therefore, measuring changes in the metabolome over time is crucial to our understanding of the factors that influence health and disease.

The longitudinal study design of the OPDC cohort, combined with the spectrum of disease stages (including REM sleep behavior disorder) will allow us to track metabolic changes with Parkinson’s disease progression.  Additionally, the ability to profile matched CSF and serum from the same patients provides us with a holistic metabolomic view. By measuring the correlation of these metabolomic biomarkers against detailed clinical and phenotypic measurements collected by the OPDC study, we hope to identify biological patterns that may predict disease progression and link this back to proteins that may be responsible for the observed pathogenesis, thereby representing strong candidates as potential therapeutic targets.          

Smriti: Tell us how biomarker identification can be beneficial for the development of new therapies in neuroscience.

Karl Bradshaw: Metabolomics is unique in its phylogenetic conservation across species, lending itself well to translation of non-human preclinical biological insights to human disease in the early stages of clinical investigations.  Metabolite biomarkers can therefore be used across the drug development process from early de-risking of the drug target (by determining the mechanism of action), through the drug candidate development program (by providing insights for pharmacokinetic and pharmacodynamic modeling, dose selection, and off-target effects), and in demonstrating clinical utility (by informing patient selection, disease stratification, and safety and efficacy assessment). Ultimately these metabolite profiles of safety and efficacy could eventually become biomarkers for a companion diagnostic to sit alongside a new therapy.

Smriti: Give our readers some insights on Metabolomics and how it helps researchers to identify the genetic variation of individuals.

Karl Bradshaw: Metabolites represent the downstream products resulting from interactions between genes, transcripts, and proteins, making metabolomics an ideal tool to assist with the integration of multi-omics data sets. Metabolites mediate many of the inhibitory and activation mechanisms influencing the genome, transcriptome, and proteome. By contributing to epigenetic regulatory mechanisms as direct substrates, cofactors, or coenzymes and by acting as ligands for nuclear receptors, metabolites directly or indirectly affect gene expression. Metabolomics serves as a first-line phenotyping tool to track alterations in metabolite levels and map them to the appropriate biochemical pathways providing a linkage from genotype to phenotype. This linkage supports the interpretation of other ‘omics' data that, when considered alone, may not translate into the observed phenotypes, resulting in misinterpretation. Through its synergism with other ‘omics approaches, metabolomics sheds new light on gene-metabolite networks, mechanisms of diseases, and drug actions.

Smriti: Are you looking for more collaborations to advance metabolomic biomarkers?

Karl Bradshaw: Yes, we are always looking for more collaborations such as the one with OPDC. We have signed around eight of these types of collaborations to date and are in discussion with many more researchers all over the world where there is a shared interest in the utility of metabolomics to provide biomarkers to further the understanding, diagnosis, and discovery of new treatments for difficult to treat diseases.

Smriti: Share your long-term goals in biomarker identification through metabolomics in neuroscience.

Karl Bradshaw: Ultimately, I would like to see metabolomics play a central role in the clinical management of multiple neurodegenerative diseases such as Parkinson’s, Alzheimer’s and other dementias, as well as Multiple Sclerosis and ALS. This would include metabolomics playing a key role in early diagnosis, treatment guidance, and treatment response tracking. 

Source: Canva

About the Author:

Karl Bradshaw is the Vice President of Corporate Development at Metabolon. He is responsible for driving the company’s growth strategy through the identification, evaluation, and execution of partnering opportunities that align with the company’s strategic goals and technical expertise. Karl has a deep understanding of global healthcare sector trends for drugs, diagnostics, tools, and devices, along with extensive experience in financial analysis. Karl earned his Ph.D. in Neuroscience from University College London (UCL) and holds an MPhil in Bioscience Enterprise from Cambridge University. 
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