Valganciclovir

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history

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