Pharmaceutical Interventions in Chronic Fatigue Syndrome: A Literature-based Commentary, by  Spencer Richman, Matthew C Morris, Gordon Broderick, Travis JA Craddock, Nancy G Klimas, Mary Ann Fletcher in Clinical Therapeutics [Available online 11 March 2019]

Research abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by prolonged periods of fatigue, chronic pain, depression, and a complex constellation of other symptoms. Currently, ME/CFS has no known cause, nor are the mechanisms of illness well understood. Therefore, with few exceptions, attempts to treat ME/CFS have been directed mainly toward symptom management.

These treatments include antivirals, pain relievers, antidepressants, and oncologic agents as well as other single-intervention treatments. Results of these trials have been largely inconclusive and, in some cases, contradictory. Contributing factors include a lack of well-designed and -executed studies and the highly heterogeneous nature of ME/CFS, which has made a single etiology difficult to define.

Because the majority of single-intervention treatments have shown little efficacy, it may instead be beneficial to explore broader-acting combination therapies in which a more focused precision-medicine approach is supported by a systems-level analysis of endocrine and immune co-regulation.

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Excerpt from Discussion:

The current literature on the treatment of ME/CFS leans strongly toward a single conclusion that there is no single solution. The assumption that a single drug can successfully treat ME/CFS is likely incorrect.

The multifaceted, complex nature of ME/CFS may instead be more effectively treated with combination therapies, tailored to the specific causes and symptoms present in each individual patient. These potential therapies will be supported by advancements in 2 fields.

First, advancements in systems biology and systems-level analysis of the biological drivers behind ME/CFS will more clearly inform researchers as to which illness mechanisms are viable targets for treatment.  Systems biology approaches have already been undertaken to analyze gene coexpression networks, perform pathway analysis, and explore metabolic pathway perturbations in ME/CFS.  Generating robust tools for system-wide analysis of ME/CFS, at all of the conventional “-omics” levels, may prove invaluable for the discovery of a treatment or cure.

While systems biology approaches are needed to conduct basic research into the underlying causes of ME/CFS, personalized medicine and translational medicine are the necessary complements to such research. Personalized or precision medicine is a field that seeks to tailor treatments to individuals or narrow groups of individuals based on genetic or epigenetic makeup as well as a variety of other nongeneralizable patient characteristics. It has been promoted by some as the future of medicine, and it may prove invaluable in treating patients with ME/CFS.

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