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Olav Mella
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[[File:Olav Mella.png|200px|right|Source:ResearchGate]] '''Olav Mella''' is an Adjunct Professor in the [[ME/CFS]] research group at the Department of Oncology and Medical Physics at the University of Bergen, Haukeland University Hospital, Bergen, Norway.He works with Dr. [[Øystein Fluge]] in the Norwegian [[Rituximab]] and [[cyclophosphamide]] trials for the depletion of [[B cell]] [[lymphocytes]] in [[ME/CFS]] patients. Dr. Mella is a member of the Working Group which offers their expertise and resources to the [[ME/CFS Collaborative Research Center at Stanford University]].<ref>{{Cite web|url=https://bos.etapestry.com/prod/viewEmailAsPage.do?erRef=773.0.423082047&databaseId=OMF&mailingId=34274682&jobRef=773.0.506425459&key=b6b9237b3ebd1e462a5d11dbc5c4dae&personaRef=773.0.423082048&memberId=1348639685 | title = OMF grants $1.2M to Ramp Up Collaborative Research Center at Stanford University|website=bos.etapestry.com|access-date=2020-05-06}}</ref> ==Rituximab work in ME/CFS== [[Øystein Fluge]]'s and Olav Mella's discovery was found by accident, in that 3 [[ME/CFS]] patients who had [[B cell|B-cell]] lymphoma improved remarkably following treatment with [[Rituximab]].Not only had their lymphomas improved, but all symptoms of their ME/CFS diminished with the treatment.The positive responses were delayed for up to 6-12 weeks, despite their B cells being eliminated by the drug in 2 weeks.Since that accidental discovery, a larger study has been undertaken. Initial reports are promising in that there is a positive response in 67% of the patients receiving Rituximab vs a 13% improvement in the placebo group. After the effects wore off, there was a decline in the numbers who responded to the second and subsequent infusions.<ref>{{Cite web|url=http://www.investinme.org/IIMEC7.shtml | title = Invest in ME Research - IIMEC7 International ME Conference 2012 | last = Invest in ME Research | first = | authorlink = Invest in ME | date = |website=[[Invest in ME Research]]|archive-url=|archive-date=|url-status=|access-date=2020-05-06}}</ref> The clinical trial, named [[RituxME]], is now a multicenter, phase III study. It is randomized, double-blind and placebo controlled, with 152 participants, of which half will receive treatments with rituximab and the other half will be treated with placebo (saline). Results will be published in 2018.<ref>http://www.helse-bergen.no/en/OmOss/Avdelinger/kreft/forsking-fagutvikling/Sider/RituxME.aspx</ref> On Nov 21, 2017, Drs. [[Øystein Fluge]] and Olav Mella announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of [[ME/CFS]] patients with an immune profile that would be responsive to Rituximab. The Drs. will publish a paper next year with the specifics of the failed trial.<ref>{{Cite web|url=http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/ | title = Norwegian Rituximab Chronic Fatigue Syndrome (ME/CFS) Trial Fails | last = Simmaron Research | first = | authorlink = Simmaron Research | date = 2017-11-26 | website = Simmaron Research|language=en-US|archive-url=|archive-date=|url-status=|access-date=2020-05-06}}</ref> The discovery of ME/CFS patients responding positively to an autoimmunity drug has radically changed how many have viewed ME/CFS, to the point that Bjørn Guldvog, the Deputy Director General of Norwegian Directorate of Health, has apologized for the way in which ME patients in Norway have been treated: "I think that we have not cared for people with ME to a great enough extent. I think it is correct to say that we have not established proper health care services for these people, and I regret that." The European ME Alliance believes that such a public apology from a governmental health agency has never occurred before.<ref>{{Cite web|url=http://www.euro-me.org/news-Q42011-003.htm | title = Norway's Directorate of Health Apologises to ME Patients for Poor Treatment | last = European ME Alliance | first = | authorlink = European ME Alliance | date = | website = euro-me.org|archive-url=|archive-date=|url-status=|access-date=2020-05-06}}</ref> In 2015, a second clinical trial for ME/CFS by the same group headed by Fluge and Mella, was started using the chemotherapy drug, cyclophosphamide. Called [[CycloME]] part A, this study will involve 40 patients with moderate and severe ME/CFS and will be ongoing until January 2017. If the results indicate a clinically relevant response, i.e., an improvement in symptoms, in a minimum of 40% of the patients, the trial will move into CycloME part B and may be extended to include patients with very severe ME.<ref>http://www.helse-bergen.no/en/OmOss/Avdelinger/kreft/forsking-fagutvikling/Sider/CycloME.aspx</ref> ==Talks and interviews== *2011, [http://me-pedia.org/wiki/Invest_in_ME_Conference 6th Invest in ME International ME Conference 2011 - B-cell Depletion Therapy Using Rituximab in ME/CFS - Part I] *2012, [http://me-pedia.org/wiki/Invest_in_ME_Conference 7th Invest in ME International ME Conference 2012 - B-cell Depletion Therapy Using Rituximab in ME/CFS - Part I] *2013, [http://me-pedia.org/wiki/Invest_in_ME_Conference 8th Invest in ME International ME Conference 2012 - B-cell Depletion Therapy Using Rituximab in ME/CFS - Part I] *2014, [https://www.youtube.com/watch?v=Yw7VIyFNH50 Olav Mella speaks about the Rituximab study and ME/CFS future] *2015, [http://www.thenakedscientists.com/HTML/interviews/interview/1001217/ The Naked Scientists Podcast -"Is ME an autoimmune disease?"] *2015, [http://www.investinme.org/IIMEC10.shtml 10th Invest in ME International ME Conference 2015 - no speech title given] *2 Jun 2017, Speaker at the 12th [[Invest in ME International ME Conference]] on "Update on the clinical trials [[RituxME]] and [[CycloME]]"<ref>{{Cite web|url=http://www.investinme.org/iimec12.shtml | title = IIMEC12 International ME Conference 2017 | last = Invest in ME Research | first = | authorlink = Invest in ME | date = |website=[[Invest in ME Research]]|archive-url=|archive-date=|url-status=|access-date=2020-05-06}}</ref> [http://www.investinme.org/iimec12.shtml DVD available] ==Notable ME/CFS Studies== *2011, Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study<ref name="Fluge, 2011">{{Cite journal | last1 = Fluge | first1 = Øystein | authorlink1 = Øystein Fluge | last2 = Bruland | first2 = Ove | authorlink2 =| last3 = Risa | first3 = Kristin | authorlink3 = | last4 = Storstein | first4 = Anette| authorlink4 = | last5 = Kristoffersen | first5 = Einar Klæboe| authorlink5 =| last6 = Sapkota | first6 = Dipak | authorlink6 =| last7 = Næss | first7 = Halvor| authorlink7 =| last8 =Dahl | first8 = Olav| authorlink8 = | last9 = Nyland | first9 = Harald Inge | authorlink9 = | last10 = Mella | first10 = Olav | authorlink10 = Olav Mella | title = Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study. | journal = PLoS One| volume = 6 | issue = 10 | page = e26358 | date = 2011 | pmid =| pmc = | doi= 10.1371/journal.pone.0026358}}</ref> - [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026358 (Full Text)] *2015, [[B cell|B-lymphocyte]] depletion in myalgic encephalopathy/chronic fatigue syndrome. An open-label phase II study with [[rituximab]] maintenance treatment<ref name="Fluge2015-II">Fluge, Ø ; Risa, K ; Lunde, S; Alme, K ; Rekeland, IG; Sapkota, D; Kristoffersen, EK; Sørland, K; Bruland, O; Dahl, O; Mella, O. 2015. B-lymphocyte depletion in myalgic encephalopathy/chronic fatigue syndrome. An open-label phase II study with rituximab maintenance treatment. ''PLoS One,10''(7):e0129898. doi: 10.1371/journal.pone.0129898</ref> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488509/ (Full Text)] *2016, Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome<ref name="Fluge, 2016">{{Cite journal | last1 = Fluge | first1 = Øystein | authorlink1 = Øystein Fluge | last2 = Mella | first2 = Olav| authorlink2 = Olav Mella | last3 = Bruland | first3 = Ove | authorlink3 = | last4 = Risa | first4 = Kristin | authorlink4 = | last5 = Dyrstad | first5 = Sissel E. | authorlink5 =| last6 = Alme | first6 = Kine| authorlink6 =| last7 = Rekeland | first7 = Ingrid G. | authorlink7 =| last8 =Sapkota | first8 = Dipak | authorlink8 = | last9 = Røsland | first9 = Gro V. | authorlink9 = | last10 = Fosså | first10 = Alexander | authorlink10 = | last11 = Ktoridou-Valen | first11 = Irini | authorlink11 = | last12 = Lunde | first12 = Sigrid | authorlink12 = | last13 = Sørland | first13 = Kari | authorlink13 = | last14 =Lien | first14 = Katarina| authorlink14 = | last15 = Herder | first15 = Ingrid | authorlink15 = | last16 = Thürmer | first16 = Hanne| authorlink16 = | last17 = Gotaas | first17 = Merete E. | authorlink17 = | last18 = Baranowska | first18 = Katarzyna A. | authorlink18 = | last19 = Bohnen | first19 = Louis M.L.J. | authorlink19 = | last20 = Schäfer | first20 = Christoph | authorlink20 = | last21 = McCann | first21 = Adrian | authorlink21 = | last22 = Sommerfelt | first22 = Kristian | authorlink22 = | last23 = Helgeland | first23 = Lars | authorlink23 = | last24 = Ueland | first24 = Per M. | authorlink24 = | last25 = Dahl | first25 = Olav | authorlink25 = | last26 = Tronstad | first26 = Karl J. | authorlink26 = Karl Tronstad| title = Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome| journal = JCI Insight | volume = 1 | issue =21| pages = | date = 2016 | pmid = | doi= 10.1172/jci.insight.89376 | url=https://doi.org/10.1172/jci.insight.89376 | page = }}</ref> [https://insight.jci.org/articles/view/89376 (Full Text)] *2016, Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome.<ref name="Lunde2016">[https://doi.org/10.1371/journal.pone.0161226 Lunde S, Kristoffersen EK, Sapkota D, Risa K, Dahl O, Bruland O, et al. (2016) Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome. PLoS ONE 11(8): e0161226. doi:10.1371/journal.pone.0161226]</ref> *2016, Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome<ref name="Loebel2016">{{Cite journal | last1 = Loebel | first1 = M | authorlink1 = Madlen Loebel | last2 = Grabowski | first2 = P | authorlink2 = Patricia Grabowski | last3 = Heidecke | first3 = H | authorlink3 = | last4 = Bauer | first4 = S | authorlink4 = | last5 = Hanitsch | first5 = LG | authorlink5 =| last6 = Wittke | first6 = K | authorlink6 =| last7 = Meisel | first7 = C | authorlink7 =| last8 =Reinke | first8 = P | authorlink8 = | last9 = Volk | first9 = H | authorlink9 = | last10 = Fluge | first10 = Ø| authorlink10 = Øystein Fluge | last11 = Mella | first11 = O | authorlink11 = Olav Mella | last12 = Scheibenbogen | first12 = C | authorlink12 = Carmen Scheibenbogen| title = Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome | url = https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-015-0628-4| journal = Brain, behavior, and immunity | volume = 52 | issue = | pages = 32-39 | pmid = 26399744 | date = 2016 | doi= 10.1016/j.bbi.2015.09.013}}</ref> - [https://www.sciencedirect.com/science/article/pii/S0889159115300209?via%3Dihub (Full Text)] *2018, Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref>{{Cite journal | last = Günther | first = Oliver P. | last2 = Gardy | first2 = Jennifer L. | last3 = Stafford | first3 = Phillip | authorlink3 = Phillip Stafford | last4 = Fluge | first4 = Øystein | authorlink4 = Øystein Fluge | last5 = Mella | first5 = Olav | authorlink5 = Olav Mella | last6 = Tang | first6 = Patrick | last7 = Miller | first7 = Ruth R. | last8 = Parker | first8 = Shoshana M. | last9 = Johnston | first9 = Stephen A. | date = 2018-10-08 | title = Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://link.springer.com/article/10.1007%2Fs12035-018-1354-8|journal=Molecular Neurobiology|language=en|volume=|pages=|doi=10.1007/s12035-018-1354-8|issn=0893-7648|via=}}</ref> [https://link.springer.com/article/10.1007/s12035-018-1354-8 (Full text)] *2018, Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome<ref>{{Cite journal | last = Schjøtt | first = Jan | authorlink = | last2 = Vries | first2 = Annick de | authorlink2 = | last3 = Mella | first3 = Olav | authorlink3 = Olav Mella | last4 = Sørland | first4 = Kari | authorlink4 = | last5 = Risa | first5 = Kristin | authorlink5 = | last6 = Alme | first6 = Kine | last7 = Fluge | first7 = Øystein | authorlink7 = Øystein Fluge | last8 = Rekeland | first8 = Ingrid G. | date = 2018-11-28 | title = Rituximab Serum Concentrations and Anti-Rituximab Antibodies During B-Cell Depletion Therapy for Myalgic Encephalopathy/Chronic Fatigue Syndrome|url=https://www.clinicaltherapeutics.com/article/S0149-2918(18)30514-9/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|pages=|doi=10.1016/j.clinthera.2018.10.019|issn=1879-114X|pmid=30502905|quote=|via=}}</ref> [https://www.sciencedirect.com/science/article/abs/pii/S0149291818305149 (Abstract)] *2019, B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial<ref>{{Cite journal | last = Fluge | first = Øystein | authorlink = Øystein Fluge | last2 = Rekeland | first2 = Ingrid G. | last3 = Lien | first3 = Katarina | last4 = Thürmer | first4 = Hanne | last5 = Borchgrevink | first5 = Pette C. | last6 = Schäfer | first6 = Christoph | last7 = Sørland | first7 = Kari | last8 = Aßmus | first8 = Jörg | last9 = Ktoridou-Valen | first9 = Irini | last10 = Mella | first10 = Olav | authorlink10 = Olav Mella | date = 2019-04-02 | title = B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial|url=http://annals.org/article.aspx?doi=10.7326/M18-1451|journal=Annals of Internal Medicine|language=en|doi=10.7326/M18-1451|issn=0003-4819}}</ref> *2020, Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref name="Asgeir2020">{{Cite journal | last = Lande | first = Asgeir | authorlink = Asgeir Lande | last2 = Fluge | first2 = Øystein | authorlink2 = Øystein Fluge | last3 = Strand | first3 = Elin B. | authorlink3 = Elin Strand | last4 = Flåm | first4 = Siri T. | authorlink4=Siri Flåm | last5 = Sosa | first5 = Daysi D. | authorlink5 = Daysi Sosa | last6 = Mella | first6 = Olav | authorlink6 = Olav Mella | last7 = Egeland | first7 = Torstein | authorlink7 = | last8 = Saugstad | first8 = Ola D. | authorlink8 = | last9 = Lie | first9 = Benedicte A. | authorlink9 = | date = 2020-03-24 | title = Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=https://www.nature.com/articles/s41598-020-62157-x|journal=Scientific Reports|language=en|volume=10|issue=1|pages=1–8|doi=10.1038/s41598-020-62157-x|issn=2045-2322|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://www.nature.com/articles/s41598-020-62157-x (Full text)] * 2020, Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study<ref name="Rekeland2020">{{Cite journal | last = Rekeland | first = Ingrid G. | authorlink = Ingrid Rekeland | last2 = Fosså | first2 = Alexander | authorlink2 = | last3 = Lande | first3 = Asgeir | authorlink3 = | last4 = Ktoridou-Valen | first4 = Irini | authorlink4 = | last5 = Sørland | first5 = Kari | authorlink5 = | last6 = Holsen | first6 = Mari | authorlink6 = | last7 = Tronstad | first7 = Karl J. | authorlink7 = Karl Tronstad | last8 = Risa | first8 = Kristin | authorlink8 = | last9 = Alme | first9 = Kine | authorlink9 = | date = 2020 | title=Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study|url=https://www.frontiersin.org/articles/10.3389/fmed.2020.00162/full|journal=Frontiers in Medicine|language=English|volume=7|issue=|pages=162|pmc=PMC7201056|pmid=32411717|doi=10.3389/fmed.2020.00162|issn=2296-858X|quote=|via= | last10 = Viken | first10 = Marte K. | authorlink10 = | last11 = Lie | first11 = Benedicte K. | authorlink11 = | last12 = Dahl | first12 = Olav | authorlink12 = | last13 = Mella | first13 = Olav | authorlink13 = Olav Mella | first14 = Øystein | last14 = Fluge | author-link14 = Øystein Fluge}}</ref> - [https://www.frontiersin.org/articles/10.3389/fmed.2020.00162/full? (Full text)] *2021, Fine mapping of the major histocompatibility complex (MHC) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggests involvement of both HLA class I and class II loci<ref name="Hajdarevic2021">{{Cite journal | last = Hajdarevic | first = Riad | authorlink = Riad Hajdarevic | last2 = Lande | first2 = Asgeir | authorlink2 = Asgeir Lande | last3 = Rekeland | first3 = Ingrid | authorlink3 = Ingrid Rekeland | last4 = Rydland | first4 = Anne | authorlink4 = Anne Rydland | last5 = Strand | first5 = Elin B. | authorlink5 = | last6 = Sosa | first6 = Daisy D. | authorlink6 = | last7 = Creary | first7 = Lisa E | last8 = Mella | first8 = Olav | authorlink8 = Olav Mella | last9 = Egeland | first9 = Torstein | authorlink9 = Egeland Torstein | date = 2021-11-01 | title = Fine mapping of the major histocompatibility complex (MHC) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suggests involvement of both HLA class I and class II loci|url=https://www.sciencedirect.com/science/article/pii/S0889159121005092|journal=Brain, Behavior, and Immunity|language=en|volume=98|issue=|pages=101–109|doi=10.1016/j.bbi.2021.08.219|issn=0889-1591|pmc=|pmid=|access-date=|quote=|via=}}</ref>[https://doi.org/10.1016/j.bbi.2021.08.219 (Full text)] ==Learn more== *2015 [http://phoenixrising.me/archives/26930 Fluge & Mella’s pre-trial study highlights life-changing potential of rituximab] ==See also== *[[Øystein Fluge]] *[[CycloME]] *[[RituxME]] ==References== {{Reflist}} [[Category:Researchers]] [[Category:Norway researchers]] [[Category:Norwegian clinicians]]
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