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Valganciclovir
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'''Valganciclovir''' (brand name '''Valcyte''') is an [[antiviral]] medication mostly used to treat [[cytomegalovirus]] [[infection]]s. It is active against a number of [[herpesvirus]]es. ==Chronic fatigue syndrome== 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 [[Jose Montoya|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 [[Epstein-Barr virus|EBV]].<ref name="Montoya, 2013" /> Valganciclovir may improve systems by via its broad spectrum antiviral activity against latent [[herpesvirus]]es, 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 [[microglia]]l activation;<ref>{{Cite journal | last =Ding | first = Zhaoqing | authorlink = Zhaoqing Ding | last2 = Mathur | first2=Vidhu | authorlink2 = Vidhu Mathur | last3=Ho | first3 = Peggy P. | author-link3 = Peggy Ho | last4 = James | first4=Michelle L. | authorlink4 = Michelle James | last5 = Lucin | first5 = Kurt M. | authorlink5 = Kurt Lucin | last6 = Hoehne | first6 = Aileen | last7 = Alabsi | first7 = Haitham | last8 = Gambhir | first8 = Sanjiv S. | last9 = Steinman | first9 = Lawrence | date = 2014-02-10 | title = Antiviral drug ganciclovir is a potent inhibitor of microglial proliferation and neuroinflammation|url=https://www.ncbi.nlm.nih.gov/pubmed/24493798|journal=The Journal of Experimental Medicine|volume=211|issue=2|pages=189–198|doi=10.1084/jem.20120696|issn=1540-9538|pmc=3920559|pmid=24493798|quote=|via= | authorlink6 = Aileen Hoehne | authorlink7 = Haitham Alabsi | authorlink8 = Sanjiv Gambhir | authorlink9 = Lawrence Steinman}}</ref> [[ME/CFS]] patients have been shown to have chronic activation of microglia.<ref name="nakatomi2014" /> However follow-up mice studies and [[In vitro studies|in vitro research]] found [[gancyclovir]] did not reduce [[microglia]]l activation.<ref>{{Cite journal | last =Skripuletz | first = Thomas | authorlink = Thomas Skripuletz | last2 = Salinas Tejedor | first2 = Laura | authorlink2 = Laura Salinas Tejedor | last3=Prajeeth | first3 = Chittappen K. | author-link3 = Chittappen Prajeeth | last4 = Hansmann | first4=Florian | authorlink4 = Florian Hansmann | last5 = Chhatbar | first5 = Chintan | authorlink5 = Chintan Chhatbar | last6 = Kucman | first6 = Valeria | last7 = Zhang | first7 = Ning | last8 = Raddatz | first8 = Barbara B. | last9 = Detje | first9 = Claudia N. | date = 2015-10-08 | title = The antiviral drug ganciclovir does not inhibit microglial proliferation and activation|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597339/|journal=Scientific Reports|volume=5|issue=|pages=|doi=10.1038/srep14935|issn=2045-2322|pmc=4597339|pmid=26447351|quote=|via= | authorlink6 = Valeria Kucman | authorlink7 = Ning Zhang | authorlink8 = Barbara Raddatz | authorlink9 = Claudia Detje}}</ref> The authors of the 2014 paper later published a follow-up paper (2017) based on in vitro and [[In vivo studies|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-[[Neuroinflammation|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."<ref>{{Cite journal | last =Mathur | first=Vidhu | author-link = Vidhu Mathur | last2=Burai | first2 = Ritwik | authorlink2 = Ritwik Burai | last3 = Vest | first3=Ryan T. | author-link3 = Ryan Vest | last4 = Bonanno | first4 = Liana N. | authorlink4 = Liana Bonanno | last5 = Lehallier | first5 = Benoit | author-link5 = Benoit Lehallier | last6 = Zardeneta | first6 = Macy | authorlink6 = Macy Zardeneta | last7 = Mistry | first7 = Karishma N. | authorlink7 = Karishma Mistry | last8 = Do | first8 = Danny | authorlink8 = Danny Do | last9 = Marsh | first9 = Samuel E. | authorlink9 = Samuel Marsh | date = 2017-12-20 | title = Activation of the STING-dependent type I interferon response reduces microglial reactivity and neuroinflammation|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806703/|journal=Neuron|volume=96|issue=6|pages=1290–1302.e6|doi=10.1016/j.neuron.2017.11.032|issn=0896-6273|pmc=5806703|pmid=29268096|quote=|via=}}</ref> ==Notable studies== *2012, Response to valganciclovir in [[chronic fatigue syndrome]] patients with human [[HHV-6|herpesvirus 6]] and [[EBV|Epstein-Barr virus]] IgG antibody titers.<ref name="Watt, 2012" /> [https://deepblue.lib.umich.edu/bitstream/handle/2027.42/94236/23411_ftp.pdf?sequence=1&isAllowed=y (Full text)] *2013, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Valganciclovir in a Subset of Patients With [[Chronic Fatigue Syndrome]]<ref name="Montoya, 2013" /> [https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.23713 (Full text)] ==Learn more== *2016, [https://cfsremission.wordpress.com/2016/04/07/valganciclovir-antiviral-and-cfs/ Valganciclovir antiviral and CFS] ==References== <references> <ref name="Watt, 2012">{{Citation | last1 = Watt | first1 = T | authorlink1 = Tess Watt | last2 = Oberfoell | first2 = S | authorlink2 = Stephanie Oberfoell | last3 = Balise | first3 = R | authorlink3 = Raymond Balise | last4 = Lunn | first4 = Mitchell R | authorlink4 = Mitchell Lunn | last5 = Kar | first5 = Aroop K | authorlink5 = Aroop Kar | last6 = Merrihew | first6 = LE | authorlink6 = Lindsey Merrihew | last7 = Bhangoo | first7 = MS | authorlink7 = Munveer Bhangoo | last8 = Montoya | first8 = JG | authorlink8 = Jose Montoya | title = Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers | journal = Journal of Medical Virology | volume = 84 | issue = 12 | page = 1967-1974 | date = 2012 | pmid = 23080504 | doi = 10.1002/jmv.23411 | url = https://deepblue.lib.umich.edu/bitstream/handle/2027.42/94236/23411_ftp.pdf?sequence=1&isAllowed=y }}</ref> <ref name="Montoya, 2013">{{Citation | last1 = Montoya | first1 = Jose G | authorlink1 = Jose Montoya | last2 = Kogelnik | first2 = Andreas M | authorlink2 = Andreas Kogelnik | last3 = Bhangoo | first3 = Munveer | authorlink3 = Munveer Bhangoo | last4 = Lunn | first4 = Mitchell R | authorlink4 = Mitchell Lunn | last5 = Flamand | first5 = Louis | authorlink5 = Louis Flamand | last6 = Merrihew | first6 = Lindsey E | authorlink6 = Lindsey Merrihew | last7 = Watt | first7 = Tessa | authorlink7 = Tess Watt | last8 = Kubo | first8 = Jessica T | authorlink8 = Jessica Kubo | last9 = Paik | first9 = Jane | authorlink9 = Jane Paik | last10 = Desai | first10 = Manisha | authorlink10 = Manisha Desai | title = Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. | journal = Journal of Medical Virology | volume = 85 | issue = 12 | page = 2101-9 | date = 2013 | pmid = 23959519 | doi = 10.1002/jmv.23713 }}</ref> <ref name="nakatomi2014">{{Citation| doi = 10.2967/jnumed.113.131045| issn = 1535-5667| volume = 55 | issue = 6| pages = 945–950| last1 = Nakatomi | first1 = Yasuhito| authorlink1 =Yasuhito Nakatomi | last2 = Mizuno | first2 = Kei | authorlink2 = | last3 = Ishii | first3 = Akira| authorlink3 = | last4 = Wada | first4 = Yasuhiro| authorlink4 = | last5 = Tanaka | first5 = Masaaki | authorlink5 = | last6 = Tazawa | first6 = Shusaku| authorlink6 = | last7 = Onoe | first7 = Kayo| authorlink7 = | last8 = Fukuda | first8 = Sanae| authorlink8 = | last9 = Kawabe | first9 = Joji | authorlink9 = | last10 = Takahashi | first10 = Kazuhiro| authorlink10 = | last11 = Kataoka | first11 = Yosky| authorlink11 = | last12 = Shiomi | first12 = Susumu| authorlink12 = | last13 = Yamaguti | first13 = Kouzi | authorlink13 = | last14 = Inaba | first14 = Masaaki | authorlink14 = | last15 = Kuratsune | first15 = Hirohiko| authorlink15 =| last16 = Watanabe | first16 = Yasuyoshi | authorlink16 = | title = Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study| journal = Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine | date = June 2014 | pmid = 24665088}}</ref> </references> [[Category:Potential treatments]] [[Category:Antivirals]]
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