Metabolomics: The Next Step in Precision Medicine

Ali Tinazli, PhD, joined Lifespin in Germany as CEO in summer 2021. He has deep knowledge of the science and business of biomedicine and health care, as well as the convergence of digital/consumer technologies and health care. Ali received his PhD in biochemistry from J.W. Goethe University in Germany and studied business at UC, Berkeley’s Haas School of Business and MIT’s Sloan School of Management. Ali was in strategic and operational roles in building new businesses at Fortune 100 companies like Sony and HP. In addition, Ali has significant entrepreneurial and hands-on knowledge of biosciences start-ups and serves as a board member and angel investor for numerous start-ups ranging from cybersecurity to oncology.

Personalized medicine may be the most important megatrend in health care, emerging as an outgrowth of the genomic and IT revolution that began more than 30 years ago. Today, using recent advanced technologies, clinicians are increasingly able to deliver early diagnostics for some disease states—often before the onset of symptoms or even of disease. This progress is making it possible to personalize treatment options based on an individual patient’s unique genetic profile, phenotype, lifestyle, and other characteristics. This will enable clinicians to precisely characterize the disease, stratify patients, and select the right treatments adapted to a disease and patient’s condition.

Currently, the use of genomics modalities, such as circulating tumor DNA (ctDNA), is quickly finding its way into normal clinical practice. The analysis of ctDNA is a rapidly advancing field in oncology and is used for disease monitoring, early detection, and genomic biomarker analysis, hastened by the need for an accurate, rapid, and predictive test that can inform treatment decisions for cancer patients. To identify early-stage cancers, it ctDNA is now being validated in clinical trials as an effective diagnostic platform.

The promise of genomics, however, is not without technical challenges: While ctDNA enables real-time genomic profiling without the need for invasive tumor biopsies, it is hindered by the low proportion of ctDNA in biofluids and the sequencing requirements needed for its accurate detection. Whole genome sequencing at a depth needed for detection is still prohibitively expensive for routine monitoring at a population level. In addition, the blood volumes required for detection are not trivial and can require up to 10 mL of blood per draw. As these technologies improve, ctDNA detection and use is expected to improve and become more cost effective.

In the meantime, a window of opportunity exists for alternative clinical approaches to detect and monitor not just cancer, but also numerous other diseases. For example, neurological or metabolic diseases cannot be addressed by genomics technologies and require other clinical modalities for testing and monitoring.

The time is ripe for new tools to complement genomics. And one of the most important and promising fields is metabolomics, which provides researchers the opportunity to get even closer to measuring the actual physiological state of an individual and potentially provide a new array of health insights.

What is metabolomics?

Essentially, metabolomics is the study of interactions that exist between myriads of continuous chemical reactions in all living beings, for instance when a human, or other living creature, converts food into energy. The chemicals, i.e., metabolic products needed to accomplish vital tasks such as moving, thinking, and growing, are called metabolites. The complete set of metabolites found within a biological sample is known as the metabolome.

At the center of metabolomics is the concept that a person’s metabolic state provides a close representation of that individual’s overall health status. This metabolic state reflects what has been encoded by the genome and modified by diet and environmental factors. Diseases distinctively impact metabolism causing specific changes in metabolic relationships, i.e., in the presence and quantity of metabolites. In the field of metabolomics, the metabolic profile of an individual is converted using advanced technology into a quantifiable readout of the biochemical state, revealing a range of variation, from normal physiology to diverse pathophysiologies, that may help identify early cancer states along with neurological diseases in a manner that is often not obvious from genomic analyses.

As clinical scientists, technologists, and clinicians continue to join together to explore and leverage the power of metabolomics as an early diagnostics and wellness tool, the potential for precision medicine may be unprecedented.