Novel Dynamic Proteomics Approaches to Investigate the Systems Level Pathology of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)
Abstract
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an extremely disabling condition, associated with prolonged bouts of fatigue often present for greater than 6 months. This can affect the ability to perform normal tasks, severely impacting on quality of life and independence. In addition, any form of physical (mild exercise) or mental (concentrating on work) exertion can lead to a worsening of symptoms. Few outside of those that have, or know someone that has CFS/ME, will be aware of this devastating condition. This is despite current estimates that CFS/ME is as common as more well-known conditions such as rheumatoid arthritis, affecting up to 2.5 million Americans. Not only this, it is becoming increasingly evident that large numbers of past and current military veterans are presenting with symptoms associated with the condition, following return from active duty. With such a high prevalence in both civilian and former service personnel, and the extensive impact of CFS/ME on the US economy as a result (estimated at $24 billion a year), there is a clear need to understand the complex causes which lead to the development of this condition. Yet even with large amounts of research into CFS/ME over recent years, we are no nearer to understanding the causes, making clinical diagnosis very difficult and the search for an effective treatment even more challenging. The main question here therefore is why are we no closer to understanding what causes CFS/ME? This issue relates to two common factors: i) CFS/ME is a complex condition affecting a number of different systems/tissues/organs in the body, and ii) in many cases of CFS/ME, the onset is sudden with someone going from fit and healthy to bed bound in a matter of days. With complexities surrounding the condition clear, a new and novel approach is needed in researching the underlying causes. In recent years, an analytical technique called proteomics has provided good promise in other clinical conditions for identifying potentially unknown factors that may be contributing to the onset of disease. Proteomics works by measuring the levels of several hundred to thousands of proteins (the compounds that make up and help control the function of our cells, enzymes, and hormones) within a sample (blood or tissue) simultaneously. By looking at the differences between the levels of these proteins in someone with the disease and a healthy control, we can potentially identify which proteins, and hence which pathways/tissues in the body, may be important in the development of the disease. However, what these proteomics techniques fail to take into account is that the metabolic processes in our body are constantly changing; a single measure at one point may completely miss key changes important to the disease cause, i.e., old proteins are getting broken down and new proteins being built to replace them, all at set rates that differ dependent on function. These systems are extremely sensitive to change and therefore disease will have a considerable impact on this carefully regulated system. If we can measure the impact a disease is having on these processes over time, we may be able to uncover previously unknown facets of the disease, which could be vital to the cause. This is possible by including something called a stable isotope tracer. These tracers are a form of naturally occurring compounds, in this case amino acids, which are the building blocks of proteins, that contain a chemically modified label. These labelled amino acids can be introduced into the human body, and we can trace where they go in the body and how quickly they are used to build different types of proteins by collecting regular samples of blood or tissue over hours, days, or weeks. If we then combine these tracers with proteomics (dynamic proteomics), we are able to measure the rate at which several hundred to thousands of proteins across multiple tissues are being built up and broken down over time, and which a
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110535
Entities
People
- Daniel Wilkinson
Organizations
- United States Army