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inflammatory processes alone might haveresulted in the acute neurological eventstermed ‘encephalitis’, so it is important toknow which was responsible. Either celltype can have harmful effects, but whereasmicroglia are probably involved directly inthe (presumably beneficial) Ab removal,the T lymphocytes are unlikely to bedirectly involved. This is importantbecause efforts in devising the next genera-tion of Aβ immunotherapy are being tar-geted at avoiding the T-lymphocytereaction, but it may be the microglial acti-vation that causes the harmful side effect.Furthermore, is harmful encephalitis necessary for removal of Aβ, or did the~95% of patients in the trial who did nothave encephalitis also experience poten-tially beneficial removal of Aβ plaques?Clearly, we still have much to learn fromthis trial.
COMPETING INTERESTS STATEMENTThe authors declare that they have no competingfinancial interests.
James A R Nicoll1,2, David Wilkinson3,Clive Holmes3, Phil Steart2,Hannah Markham1,2 & Roy O Weller1,2
1Division of Clinical Neurosciences, Universityof Southampton, Southampton GeneralHospital, Southampton, SO16 6YD, UK.2Neuropathology, Department of Pathology,Southampton General Hospital, Southampton,SO16 6YD, UK. 3Division of ClinicalNeurosciences, University of Southampton,Memory Assessment and Research Centre,Moorgreen Hospital, Southampton,SO30 3JB, UK.e-mail: [email protected]
1. Nicoll, J.A. et al. Nat. Med. 9, 448–452 (2003).2. DiCarlo, G., Wilcock, D., Henderson, D., Gordon, M.
& Morgan, D. Neurobiol. Aging 22, 1007–1012 (2001).3. Nakagawa, Y. et al. Exp. Neurol. 163, 244–252
(2000).4. Macfarlane, D.P., Nicoll, J.A.R., Smith, C. & Graham,
D.I. NeuroReport 10, 1–4 (1999). 5. Nicoll, J.A., Roberts, G.W. & Graham, D.I. Nat. Med.
1, 135–137 (1995).6. Wilcock, D.M. et al. J. Neurosci. 23, 3745–3751
(2003).7. Janus, C. et al. Nature 408, 979–982 (2000).8. Hock, C. et al. Neuron 38, 547–554 (2003).9. Ferrer, I. et al. Brain Pathol. 14, 11–20 (2004).
NATURE MEDICINE VOLUME 10 | NUMBER 2 | FEBRUARY 2004 119
To the editor:We are writing on behalf of the EthicsCommittee of the International Xeno-transplantation Association (IXA). Ourcommittee recently expressed concernabout the need for international guidelinesfor overseeing clinical xenotransplanta-tion. We have published letters in scientificjournals and corresponded with represen-tatives of the World Health Organization(WHO) regarding these concerns. Al-though clinical xenotransplantation pro-vides a potentially promising solution tothe shortage of human organs and tissues,the potential to introduce new infectionsfrom xenogeneic source animals into thehuman populace is a concern that man-dates extreme caution. In view of this risk,considerable effort has gone into the devel-opment of guidelines and oversight proce-dures for husbandry of source animals andrecipient monitoring in several countries.However, clinical xenotransplantation isalso carried out in countries lacking suchguidelines and oversight. Some of thesetransplants are commercial enterprisesproviding cosmetic and medical treat-ments, whereas others are clinical trials.Given that individuals may freely travelfrom one country to another to undergosuch procedures, international cooperationis needed to develop universal oversight
procedures and standards, including ethi-cal and monitoring guidelines.
Last October, international health offi-cials representing more than 20 memberstates, members of the transplantationcommunity and WHO representatives metin Madrid to discuss policies on transplan-tation. This meeting resulted in a report bythe WHO secretariat, which has recentlybeen published online (http://www.who.int/gb/EB_WHA/PDF/EB113/eeb11314.pdf).This document includes a draft resolutionto be considered by the WHO’s executiveboard in January 2004. The draft resolutionrecognizes both the potential benefit andthe potential infectious risks associatedwith xenotransplantation. Most impor-tantly, it urges the adoption of appropriateregulation and surveillance of xenotrans-plantation by national health authorities ofmember states, as well as the developmentof protective measures to prevent trans-mission of infections that may arise afterxenotransplantation. Member states arefurther urged to support international col-laboration on the prevention and surveil-lance of infections resulting fromxenotransplantation. Our committee be-lieves that adopting all of these measureswould be of enormous value in minimizingthe potential risks of xenotransplantation.The draft resolution further requests that
the WHO’s director-general support suchinternational cooperation, create a globalevidence base for evaluation of xenotrans-plantation practices, and provide technicalassistance and expertise to supportxenotransplantation efforts and oversightin member states.
The IXA’s ethics committee is highlyencouraged by the drafting of this resolutionand strongly urges its adoption by theWHO’s executive board. If this resolution is ultimately adopted by the fifty-seventhWHO assembly, it will be a major steptoward minimizing infectious risks associ-ated with xenotransplantation. Withoutorganized international cooperation, thebest efforts at minimizing these risks incountries with appropriate regulatory over-sight may be thwarted by the free travel ofindividuals undergoing unmonitored xeno-transplantation in countries lacking suchregulation.
Megan Sykes1, Mauro Sandrin2 & Emanuele Cozzi3
1Massachusetts General Hospital/HarvardMedical School, Boston, Massachusetts 02129,USA. 2Austin Repatriation Medical Center,Austin Research Institute, Heidelberg, VIC3084, Australia. 3Department of Surgery &Medical Sciences, Clinica Chirurgica IV,University of Padua, Padova 35128, Italy.e-mail: [email protected]
International cooperation on xenotransplantation
tive function over 12 months, whereaspatients who did not produce such anti-bodies continued to show cognitivedecline8. It is tempting to speculate that inthe patients who produced plaque-bindingantibodies, Aβ was removed from thebrain, and this stablized cognitive func-tion.
We were careful to point out that someor all of the features we described mighthave been a chance finding unrelated toimmunization1. However, the brains ofadditional patients immunized in the Elantrial are now being examined (ref. 9 and E.Masliah, personal communication), andshow essentially the same findings1. Thesedata provide strong evidence that removalof Aβ plaques is a direct consequence ofimmunization, although we agree that thedetailed mechanisms of Aβ removal remainto be established.
We described two different types of braininflammation microglial activation and T-lymphocyte infiltration1. Either of these
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