Updated: Apr 29
Scientific advancements have drastically improved our understanding of chronic diseases. Unfortunately, many patients suffering from chronic diseases remain unsatisfied because most therapeutic advances have focused on symptom management, rather than towards addressing a potential root cause of the disease.
Virios Therapeutics (Nasdaq: VIRI) is a development-stage biotechnology company focused on advancing novel antiviral therapies to treat debilitating chronic diseases, such as fibromyalgia (“FM”). Immune responses in response to the activation of tissue resident herpes virus have been postulated as a potential root cause triggering and/or sustaining chronic illnesses such as FM, irritable bowel disease (“IBS”), and chronic fatigue syndrome (ME/CFS), all of which are characterized by waxing and waning symptoms with no obvious etiology.
Evidence is accumulating that implicates viral infection in chronic diseases
It has been suspected for many years that tissue resident virus may play a role in a number of these chronic conditions. Data that have emerged over the last decade support the idea that chronic diseases may emerge, at least in part, due to activation of a previously dormant viral infection. Specifically, researchers have hypothesized that following initial infection, viruses that remain dormant for months or years can become reactivated in response to stress when the immune system may be less effective at suppressing resident virus. The activated virus and/or the immune response to the activated infection, may contribute to chronic diseases.[1–4]
Viruses in the herpes family have the ability to remain latent, in a dormant state, after the initial infection. An example is the Herpes varicella virus (HHV-3) that causes common “chicken pox”, which becomes latent after the initial infection but if reactivated by stress or certain environmental conditions will cause shingles. This characteristic of herpes viruses portend their potential involvement in the development of chronic diseases and or as a catalyst for symptoms or sequelae associated with several chronic disease.
Human herpesvirus 4 (HHV-4), or Epstein-Barr virus (EBV), is increasingly being investigated as having a potential role in multiple chronic diseases including certain cancer types, multiple sclerosis, lupus, and chronic fatigue syndrome. Additionally, the presence of herpes simplex virus type 1 (HSV-1) in the brain has led to other important discoveries, including that HSV-1-seropositivity increases the risk for Alzheimer’s disease and cognitive dysfunction even in those who do not develop dementia.7 Another member of the herpes family - human herpes virus-6 (HHV-6) - can lead to nerve damage, which may underlie common disease symptoms.
Antiviral medications are showing promise for treating chronic diseases
Based on the research suggesting that activated viral infections may lead to chronic disease, scientists have begun testing whether antiviral treatments may impact both the symptoms and course of relevant diseases. Fibromyalgia is one area where there is evidence that suppressive antiviral therapy may hold clinical promise. The cause of FM has thus far largely eluded scientists. Scientists and clinicians can agree that FM patients exhibit a problem with central pain processing- that is how the brain handles sensory input. The exact nature of the heightened pain sensitivity in fibromyalgia patients is poorly understood; nonetheless, it is generally believed that the central sensitization is secondary to some combination of genetic and environmental factors that predisposes the patient. Though the drugs currently approved to manage fibromyalgia target pain transmission or inhibition, they leave many patients without adequate relief and/or are not well tolerated.[5,9–12]
Virios Therapeutics’ lead development candidate (“IMC-1”) is a novel, proprietary, fixed dose combination of famciclovir and celecoxib, designed to synergistically suppress herpes virus replication, with the end goal of reducing virally promoted disease sequelae. IMC-1 has been granted fast track designation by the FDA and is currently being tested in a multi-center, randomized, double-blind, placebo-controlled Phase 2b trial (“FORTRESS”) of over 400 patients designed to set the stage for registrational studies. Evidence of IMC-1’s efficacy on a broad spectrum of FM outcome measures was previously demonstrated in a Phase 2a clinical trial.
Recent clinical trial data, presented at the European Congress of Rheumatology EULAR Congress and the IASP World Congress on Pain last year, have shown that treating FM patients with IMC-1 significantly reduced fibromyalgia symptoms, including not only pain but also fatigue, stiffness, depression, anxiety, memory problems, and sleep disturbances.[5,13,14] Importantly, IMC-1 treated patients also exhibited a lower drop-out rate due to adverse events, when compared to placebo treated patients.
Emerging data are helping to address pressing questions, including some related to COVID-19
Equipped with a deeper understanding of the potential connection between viral infection and chronic disease symptoms, researchers can now apply these principles to address novel and timely challenges such as those we are facing with COVID-19. During the pandemic, research into the etiology of long-COVID has revealed that rather than a direct result of SARS-CoV-2, long-COVID may instead result from Herpes virus reactivation that occurs secondary to COVID-19 infection.16 It is thought that the reactivation may occur due to the acute depletion of T-cells that can occur with COVID-19 and that antiviral therapy may therefore benefit those suffering from long-COVID.[16,17]
Virios Therapeutics is pursuing a second development candidate, IMC-2 (valacyclovir and celecoxib), as a potential treatment for managing the fatigue, sleep, attention, pain, autonomic function and anxiety associated with Long COVID, otherwise known as Post-Acute Sequelae of COVID-19 (PASC). The Company has provided Bateman Horne Center (“BHC”) with an unrestricted grant to conduct this study. BHC is a non-profit, interdisciplinary Center of Excellence advancing the diagnosis and treatment of ME/CFS, FM, post-viral syndromes, and related comorbidities.
It is becoming increasingly recognized that viral infection may be associated with chronic disease development, and new research is helping to elucidate the specific relationships between individual viruses and particular chronic diseases. Ongoing clinical trials are also helping to determine what combinations of antiviral treatments we can effectively deploy to interrupt the ability of these viruses to cause long-term harm and chronic symptoms in those who have been previously infected.
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2. Kaufman HE, Azcuy AM, Varnell ED, Sloop GD, Thompson HW, Hill JM. HSV-1 DNA in tears and saliva of normal adults. Invest Ophthalmol Vis Sci. 2005;46(1):241-247. doi:10.1167/IOVS.04-0614
3. Vere Hodge RA, Cheng YC. The mode of action of penciclovir: http://dx.doi.org/101177/09563202930040S601. 2016;4(1):13-24. doi:10.1177/09563202930040S601
4. Bond PA. A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders. Medical Hypotheses. 1993;40(5):301-308. doi:10.1016/0306-9877(93)90010-N
5. Pridgen WL, Duffy C, Gendreau JF, Gendreau RM. A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia. J Pain Res. 2017;10:451-460. doi:10.2147/JPR.S127288
6. Can we vaccinate against Epstein-Barr, the virus you didn’t know you had? | Science | The Guardian. Accessed March 27, 2022. https://www.theguardian.com/science/2022/mar/20/can-we-vaccinate-against-epstein-barr-virus-multiple-sclerosis-cancer
7. Itzhaki RF. Corroboration of a major role for herpes simplex virus type 1 in Alzheimer’s disease. Front Aging Neurosci. 2018;10(OCT). doi:10.3389/FNAGI.2018.00324
8. Krumina A, Chapenko S, Kenina V, et al. The role of HHV-6 and HHV-7 infections in the development of fibromyalgia. J Neurovirol. 2019;25(2):194-207. doi:10.1007/S13365-018-0703-8
9. Chinn S, Caldwell W, Gritsenko K. Fibromyalgia pathogenesis and treatment options update. Curr Pain Headache Rep. 2016;20(4):1-10. doi:10.1007/S11916-016-0556-X
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11. Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014;311(15):1547-1555. doi:10.1001/JAMA.2014.3266
12. Bellato E, Marini E, Castoldi F, et al. Fibromyalgia Syndrome: Etiology, pathogenesis, diagnosis, and treatment. Pain Research and Treatment. 2012;2012:17. doi:10.1155/2012/426130
13. Pridgen W, Duffy C, Gendreau J, Gendreau R. IMC-1, a fixed dose combination of famciclovir and celecoxib, improves common symptoms associated with fibromyalgia in addition to pain: Post hoc analysis of a phase 2a trial. In: European Congress of Rheumatology EULAR Congress. ; 2021.
14. Pridgen W, Duffy C, Gendreau J, Gendreau R. The safety of IMC-1 in patients with fibromyalgia: Phase 2a study results. In: IASP World Congress on Pain. ; 2021.
15. Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science (1979). 2022;375(6578):296-301. doi:10.1126/SCIENCE.ABJ8222/SUPPL_FILE/SCIENCE.ABJ8222_MDAR_REPRODUCIBILITY_CHECKLIST.PDF
16. Gold JE, Okyay RA, Licht WE, Hurley DJ. Investigation of long COVID prevalence and its relationship to Epstein-Barr Virus reactivation. Pathogens. 2021;10(6). doi:10.3390/PATHOGENS10060763
17. Groff D, Sun A, Ssentongo AE, et al. Short-term and long-term rates of postacute sequelae of SARS-CoV-2 infection: A systematic review. JAMA Netw Open. 2021;4(10). doi:10.1001/JAMANETWORKOPEN.2021.28568