Valganciclovir

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Valganciclovir (brand name Valcyte) is an antiviral medication mostly used to treat cytomegalovirus infections. It is active against a number of herpesviruses.

Chronic fatigue syndrome[edit | edit source]

Valganciclovir is used off-label to treat patients with ME/CFS. Studies have shown mixed evidence of efficacy.[citation needed] In a 2013 study by Montoya, et al, some improvement using valganciclovir was reported in a subset of ME/CFS patients with elevated IgG antibody titers against Human herpesvirus 6 and EBV.[1]

Valganciclovir may improve systems by via its broad spectrum antiviral activity against latent herpesviruses, which may reactivate in immunocompromised patients, including ME/CFS patients.[citation needed]

Valganciclovir became of additional interest as a potential ME/CFS treatment, particularly as an anti-inflammatory, when a 2014 study in mice suggested gancyclovir (the compound that valganciclovir converts to) reduced microglial activation;[2] ME/CFS patients have been shown to have chronic activation of microglia.[3] However follow-up mice studies and in vitro research found gancyclovir did not reduce microglial activation.[4]

The authors of the 2014 paper later published a follow-up paper (2017) based on in vitro and in vivo experiments using ganciclovir. This time they found a potentially pro-inflammatory response, specifically that ganciclovir, in sufficient doses, might stimulate a type-I interferon response in microglia. The authors attributed this response to a DNA-sensing protein called STING. While this result might appear to contradict their earlier anti-neuroinflammatory finding, they suggest it could indicate ganciclovir (GCV) "can exhibit dual function in microglia [...]: in naïve state, GCV induces microglia to be 'primed'; on the other hand, GCV reduces inflammation in active microglia."[5]

Notable studies[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. ↑ 1.0 1.1 Montoya, Jose G; Kogelnik, Andreas M; Bhangoo, Munveer; Lunn, Mitchell R; Flamand, Louis; Merrihew, Lindsey E; Watt, Tessa; Kubo, Jessica T; Paik, Jane; Desai, Manisha (2013), "Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome.", Journal of Medical Virology, 85 (12): 2101-9, doi:10.1002/jmv.23713, PMID 23959519
  2. ↑ Ding, Zhaoqing; Mathur, Vidhu; Ho, Peggy P.; James, Michelle L.; Lucin, Kurt M.; Hoehne, Aileen; Alabsi, Haitham; Gambhir, Sanjiv S.; Steinman, Lawrence (February 10, 2014). "Antiviral drug ganciclovir is a potent inhibitor of microglial proliferation and neuroinflammation". The Journal of Experimental Medicine. 211 (2): 189–198. doi:10.1084/jem.20120696. ISSN 1540-9538. PMC 3920559. PMID 24493798.
  3. ↑ Nakatomi, Yasuhito; Mizuno, Kei; Ishii, Akira; Wada, Yasuhiro; Tanaka, Masaaki; Tazawa, Shusaku; Onoe, Kayo; Fukuda, Sanae; Kawabe, Joji; Takahashi, Kazuhiro; Kataoka, Yosky; Shiomi, Susumu; Yamaguti, Kouzi; Inaba, Masaaki; Kuratsune, Hirohiko; Watanabe, Yasuyoshi (June 2014), "Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study", Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 55 (6): 945–950, doi:10.2967/jnumed.113.131045, ISSN 1535-5667, PMID 24665088
  4. ↑ Skripuletz, Thomas; Salinas Tejedor, Laura; Prajeeth, Chittappen K.; Hansmann, Florian; Chhatbar, Chintan; Kucman, Valeria; Zhang, Ning; Raddatz, Barbara B.; Detje, Claudia N. (October 8, 2015). "The antiviral drug ganciclovir does not inhibit microglial proliferation and activation". Scientific Reports. 5. doi:10.1038/srep14935. ISSN 2045-2322. PMC 4597339. PMID 26447351.
  5. ↑ Mathur, Vidhu; Burai, Ritwik; Vest, Ryan T.; Bonanno, Liana N.; Lehallier, Benoit; Zardeneta, Macy; Mistry, Karishma N.; Do, Danny; Marsh, Samuel E. (December 20, 2017). "Activation of the STING-dependent type I interferon response reduces microglial reactivity and neuroinflammation". Neuron. 96 (6): 1290–1302.e6. doi:10.1016/j.neuron.2017.11.032. ISSN 0896-6273. PMC 5806703. PMID 29268096.
  6. ↑ Watt, T; Oberfoell, S; Balise, R; Lunn, Mitchell R; Kar, Aroop K; Merrihew, LE; Bhangoo, MS; Montoya, JG (2012), "Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers" (PDF), Journal of Medical Virology, 84 (12): 1967-1974, doi:10.1002/jmv.23411, PMID 23080504

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

microglia A type of immune cell, called a macrophage, that lives in the brain. For historical reasons, macrophages have different names based on the part of the body that they normally live in. Macrophages that normally live in the blood are called monocytes. Macrophages that normally live in the skin are called Langerhans cells. Macrophages that normally live in the liver are called Kupffer cells. And macrophages that normally live in the central nervous system are called microglia. Microglia were originally classified as glial cells, under the assumption that the cells had a merely structural function, before it was realized that the cells were in fact immune cells. As the "sentinel cells" of the central nervous system, microglia survey their environment for abnormalities such as infection or tissue damage, and then initiate an immune response to fight the infection or repair the tissue damage.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

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