Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Where will the drugs come from?, by Peter L Toogood, Daniel J Clau, Sameer Phadke, DavidHoffman in Pharmacological Research [doi.org/10.1016/j.phrs.2021.105465] 30 January 2021
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating disease characterized by severe and disabling fatigue that fails to improve with rest; it is commonly accompanied by multifocal pain, as well as sleep disruption, and cognitive dysfunction. Even mild exertion can exacerbate symptoms.
The prevalence of ME/CFS in the U.S. is estimated to be 0.5-1.5% and is higher among females. Viral infection is an established trigger for the onset of ME/CFS symptoms, raising the possibility of an increase in ME/CFS prevalence resulting from the ongoing COVID-19 pandemic.
Current treatments are largely palliative and limited to alleviating symptoms and addressing the psychological sequelae associated with long-term disability. While ME/CFS is characterized by broad heterogeneity, common features include immune dysregulation and mitochondrial dysfunction. However, the underlying mechanistic basis of the disease remains poorly understood.
Herein, we review the current understanding, diagnosis and treatment of ME/CFS and summarize past clinical studies aimed at identifying effective therapies. We describe the current status of mechanistic studies, including the identification of multiple targets for potential pharmacological intervention, and ongoing efforts towards the discovery of new medicines for ME/CFS treatment.
While ME/CFS remains a poorly understood disease, there is a growing understanding of its mechanistic roots. New research directions are emerging with the potential to generate better diagnostic tools, biomarkers and pharmacological treatments. Approaches to therapy under investigation are directed at specific molecular or cellular irregularities associated with ME/CFS such as autoantibodies, immune dysregulation (e.g. NK cell function) or mitochondrial dysfunction. Recent discoveries suggest the possibility of target-based drug discovery programs directed against specific proteins implicated in either the initiation or propagation of ME/CFS symptoms (e.g. PDHK).
These developments are occurring at the same time as advances in the diagnosis and detection of ME/CFS. Investments in patient profiling and tool generation are starting to yield fruit, and we anticipate the availability of reliable clinical diagnostic tools in the near future.
Despite its significant human cost and economic impact, ME/CFS research has yet to attract major financial support.
Recognizing this deficiency, the U.S. National Institutes of Health (NIH) have established a Trans-NIH ME/CFS working group to coordinate a multi-institute effort to learn about and treat this disease. Nonetheless with an overall budget of ∼$42Bn, NIH’s spend on ME/CFS research in 2019 amounted to only ∼$15 M compared to $111 M on multiple sclerosis and $94 M on rheumatoid arthritis, both conditions for which there are multiple drugs already on the market.
Various private foundations and patient groups have been established to help support research and to advocate for increased government support, and these continue to play an essential role in increasing awareness and funding for the ME/CFS field (see for example Solve M.E. and ME Action).
However, at the current time, interest among pharmaceutical companies and biotech/venture investors appears to be almost non-existent. It is to be hoped that increased awareness of the basis and impact of ME/CFS will stimulate the investment in research that will be necessary for development of effective new therapies.