Editing Progressive multifocal leukoencephalopathy (section)

==Treatment==
No drugs effectively inhibit or cure the virus infection without toxicity. Therefore, treatment aims at reversing the immune deficiency to slow or stop the disease progress. In patients on immunosuppression, this means stopping the drugs or using plasma exchange to accelerate the removal of the biologic agent that put the person at risk for PML.<ref name=NIH/>

In HIV-infected people, this may mean starting [[antiretroviral drug|highly active antiretroviral therapy]] (HAART). AIDS patients starting HAART after being diagnosed with PML tend to have a slightly longer survival time than patients who were already on HAART and then develop PML.<ref>{{cite journal | year = 2004 | title = Progressive multifocal leukencephalopathy in patients on highly active antiretroviral therapy: survival and risk factors of death | journal = Journal of Acquired Immune Deficiency Syndromes | volume = 37 | issue = 2| pages = 1263–1268 | pmid = 15385733 | doi = 10.1097/01.qai.0000136093.47316.f3 | last1 = Wyen | first1 = Christoph | last2 = Hoffmann | first2 = Christian | last3 = Schmeier | first3 = Norbert | last4 = Hoffmann | first4 = Andrej | last5 = Qurishi | first5 = Nazifa | last6 = Rockstroh | first6 = Jürgen | last7 = Esser | first7 = Stefan | last8 = Rieke | first8 = Ansgar | last9 = Ross | first9 = Birgit | last10 = Lorenzen | first10 = Thore | last11 = Schmitz | first11 = Karina | last12 = Stenzel | first12 = Werner | last13 = Salzberger | first13 = Bernd | last14 = Fätkenheuer | first14 = Gerd | s2cid = 23613081 | doi-access = free }}</ref> Some AIDS patients with PML have been able to survive for several years, with HAART.<ref>{{cite journal |last1=Gray |first1=Françoise |last2=Salmon |first2=Dominique |last3=Thiebault |first3=Jean Baptiste |last4=Gasnault |first4=Jacques |last5=Bienvenu |first5=Boris |last6=Vendrely |first6=Aurélie |s2cid=23865244 |title=Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy |journal=Acta Neuropathologica |volume=109 |issue=4 |pages=449–455 |ref=21|doi=10.1007/s00401-005-0983-y |pmid=15739098 |year=2005 }}</ref> A rare complication of effective HAART is [[immune reconstitution inflammatory syndrome]] (IRIS), in which increased immune system activity actually increases the damage caused by the JCV infection; although IRIS can often be managed with medication, it is extremely dangerous in PML.<ref>{{cite journal |title=Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy |journal=Acta Neuropathol. |volume=109 |issue=4 |pages=449–55 |date=April 2005 |pmid=15739098 |doi=10.1007/s00401-005-0983-y |last1=Vendrely  |first1=Aurélie  |last2=Bienvenu  |first2=Boris  |last3=Gasnault  |first3=Jacques  |last4=Thiebault  |first4=Jean Baptiste  |last5=Salmon  |first5=Dominique  |last6=Gray  |first6=Françoise|s2cid=23865244 }}</ref>

[[Cidofovir]] was studied as possible treatment for PML<ref name="pmid11408993">{{cite journal |title=Use of cidofovir in progressive multifocal leukoencephalopathy |journal=Ann Pharmacother |volume=35 |issue=6 |pages=741–4 |date=June 2001 |pmid=11408993 |doi=10.1345/aph.10338 |url=http://www.theannals.com/cgi/pmidlookup?view=long&pmid=11408993 |last1=Segarra-Newnham |first1=Marisel |last2=Vodolo |first2=Kristen M |s2cid=32026770 }}{{dead link|date=April 2018 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> and has been used on a case-by-case basis, working in some, but not others.

[[Cytarabine]] (also known as ARA-C), a chemotherapy drug used to treat certain cancers, has been prescribed on an experimental basis for a small number of non-AIDS PML patients, and stabilized the neurological condition of a minority of these patients.<ref>{{cite journal |title=Treatment of non-AIDS progressive multifocal leukoencephalopathy with cytosine arabinoside |journal=J. Neurovirol. |volume=7 |issue=4 |pages=386–90 |date=August 2001 |pmid=11517422 |doi= 10.1080/13550280152537292|last1=Aksamit |first1=A J|s2cid=12159275 }}</ref>  One patient regained some cognitive function lost as a result of PML.<ref>{{cite journal  |title=Progressive multifocal leukoencephalopathy in a patient treated with natalizumab |journal=N. Engl. J. Med. |volume=353 |issue=4 |pages=375–81 |date=July 2005 |pmid=15947078 |doi=10.1056/NEJMoa051847 |last1=Langer-Gould  |first1=Annette  |last2=Atlas  |first2=Scott W.  |last3=Green  |first3=Ari J.  |last4=Bollen  |first4=Andrew W.  |last5=Pelletier  |first5=Daniel|doi-access=free}}</ref>

In June 2010, the first [[case report]] appeared of a PML patient being successfully treated with the antimalarial drug [[mefloquine]] with activity against the JC virus. The patient cleared the virus and had no further neurological deterioration.<ref>{{cite journal |title=Mefloquine in the treatment of progressive multifocal leukoencephalopathy |journal= J Neurol Neurosurg Psychiatry |volume= 82|issue= 4|pages= 452–455|date=June 2010 |pmid= 20562463|doi= 10.1136/jnnp.2009.190652|url=http://jnnp.bmj.com/content/early/2010/06/19/jnnp.2009.190652.full |last1=Gofton |first1=T. E. |last2=Al-Khotani |first2=A. |last3=O'Farrell |first3=B. |last4=Ang |first4=L. C. |last5=McLachlan |first5=R. S.|s2cid= 19877728 }}</ref> Two case reports of using [[interleukin-2]] successfully have been published.<ref>{{cite journal|author1=Buckanovich RJ1, Liu G, Stricker C|s2cid=24949477|title=Nonmyeloablative allogeneic stem cell transplantation for refractory Hodgkin's lymphoma complicated by interleukin-2 responsive progressive multifocal leukoencephalopathy.|journal=Ann Hematol|date=July 2002|volume=81|issue=7|pages=410–3|pmid=12185517|doi=10.1007/s00277-002-0481-4|display-authors=etal}}</ref> Some success have been reported with [[mirtazapine]], but this has not been demonstrated in clinical trials.<ref>{{cite journal|last1=Jamilloux|first1=Y|last2=Kerever|first2=S|last3=Ferry|first3=T|last4=Broussolle|first4=C|last5=Honnorat|first5=J|last6=Sève|first6=P|s2cid=34008609|title=Treatment of Progressive Multifocal Leukoencephalopathy With Mirtazapine.|journal=Clinical Drug Investigation|date=October 2016|volume=36|issue=10|pages=783–9|pmid=27401779|doi=10.1007/s40261-016-0433-8}}</ref>
A number of drugs work against JC virus in [[cell culture]], but no proven, effective therapy is known in humans.<ref>{{cite journal |title=Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. |journal=Clin. Microbiol. Rev. |volume=25 |issue=3 |pages=471–506 |date=July 2012 |pmid=22763635 |doi= 10.1128/CMR.05031-11|last1=Ferenczy |first1=MW | last2 = Marshall | first2 = LJ | last3 = Nelson | first3 = CD | last4 = Atwood | first4 = WJ | last5 = Nath | first5 = A | last6 = Khalili | first6 = K | last7 = Major | first7 = EO | pmc=3416490}}</ref>
For example, [[Brincidofovir]] (1-O-hexadecyloxypropyl-cidofovir /CMX001) available as Tembexa, suppresses JCV,<ref>{{cite journal |title=CMX001 (1-O-hexadecyloxypropyl-cidofovir) inhibits polyomavirus JC replication in human brain progenitor-derived astrocytes. |journal=Antimicrob. Agents Chemother. |volume=55 |issue=5 |pages=2129–36 |date=May 2011 |pmid= 21402853 |doi=10.1128/AAC.00046-11|last1 = Gosert | first1 = R | last2 = Rinaldo | first2 = C.H. | last3 = Wernil | first3 = M | last4 = Major | first4 = EO| last5 = Hirsch | first5 = HH | pmc=3088264}}</ref> but has been found to have toxicity at therapeutic dosage.<ref>{{cite journal |last1=Rainer |first1=Gosert |last2=Rinaldo |first2=Christine |last3=Wernli |first3=Marion |last4=Major |first4=Eugene |last5=Hirsch |first5=Hans |title=CMX001 (1-O-Hexadecyloxypropyl-Cidofovir) Inhibits Polyomavirus JC Replication in Human Brain Progenitor-Derived Astrocytes |journal=Antimicrobial Agents and Chemotherapy |volume=55 |issue=5 |pages=2129–2136 |pmc=3088264 |year=2011 |pmid=21402853 |doi=10.1128/AAC.00046-11 }}</ref>
Infusion of donor T cells specific to the related BK polyomavirus has shown possible effect in treating PML in one small study by Katy Rezvani's group, but needs further study.<ref>{{Cite journal|last1=Muftuoglu|first1=Muharrem|last2=Olson|first2=Amanda|last3=Marin|first3=David|last4=Ahmed|first4=Sairah|last5=Mulanovich|first5=Victor|last6=Tummala|first6=Sudhakar|last7=Chi|first7=T. Linda|last8=Ferrajoli|first8=Alessandra|last9=Kaur|first9=Indreshpal|display-authors=3|date=2018-10-11|title=Allogeneic BK Virus–Specific T Cells for Progressive Multifocal Leukoencephalopathy|journal=New England Journal of Medicine|language=en|volume=379|issue=15|pages=1443–1451|doi=10.1056/nejmoa1801540|pmid=30304652|pmc=6283403|issn=0028-4793}}</ref>
In December 2021, Cellevolve announced it is launching a clinical trial for the treatment of PML utilizing BK virus specific T-cells (VSTs).<ref>{{cite web |title=Cellevolve Announces Global Partnership with QIMR Berghofer Medical Research Institute to Advance Novel Off-the Shelf T-cell Therapy in the First Randomized Cell Therapy Trial for Progressive Multifocal Leukoencephalopathy (PML) |url=https://www.businesswire.com/news/home/20211201005654/en/Cellevolve-Announces-Global-Partnership-with-QIMR-Berghofer-Medical-Research-Institute-to-Advance-Novel-Off-the-Shelf-T-cell-Therapy-in-the-First-Randomized-Cell-Therapy-Trial-for-Progressive-Multifocal-Leukoencephalopathy-PML |website=BUSINESS WIRE |date=December 2021 |access-date=3 May 2022}}</ref>