post-lyme-disease syndrome under trial

1
DNA polymoq~hic,nm'kers In this case. becanse the donor was female. "all we had to do ~as h+ok at calls to see if they can'ied ma~e or i)malc chmmos~mes,"explains Dr Paul Veys i Consuhant in Paediatric Bone Man'ow Tnmsphnts. GOS } l;atare uses for cord blood cells fl:dudc their use as vehicles for gone therapy in child+onwith immunedeficiencies, ntetabolic diseases and conditions such an thalassaemia and sickle cell disease. But Veys believes that related-donor cord blood transplants will not prove such a viable option fur treating patients with leukaemia because the so-called graft-versus-leukaemia effect, which is useful in these situations, might be rcd|~ccd when a~smg n~atcbed-co~d ce]],~ as opposed to bo~lc +1~ar|o¢, cdls. A Phase l pih,t s~{~dy, c+.aTenfly trader way at ihc N,ai¢u.+ai 1+~qitmes of Health ~Bet~tesda. MD t !SA}. is ]n the process of administering gone dxcrap3 ~o three patict~s with group C Fancon]'~ anaemia. The s~ady,led by Johnson Liu. involves using a relrovinfivectorto h~u-mduce the nomrd form of the gene into stem cells derived from autologous peripheral b~ood.Dr lnderjeet Dokai ¢Consuhant Paediatric Haematologist,The Hammersmith Hospital London, UKI has recruited a patient for this s~.~dy,and believe,~that certain t~a~ures of Fanconi's anaemia compared with other diseases The long-term finical effects of Lyme disease are under investigation in the USA in a double-blind, randomized, placebo-controlled trial of antibiotic treatment for patients with post-Lyme+diseasesyndrome. Lyme disease ~ u r s in temperate regions worldwide and results from infection by the spirochaete bacterium Bormlia burgdorfe~i. This nficroorganismis carried and spread by infected ticks that feed on humans, dogs, deer and mice; their habitats include grass, shrubs and woodland. The incidence of the disease is particularly high in northeastern USA (up to 45 cases per 100 060 people per year) whereas in Europe there are only 1.4 ea~s and in the UK only 0.14 per ! ~ @10. Tick bites am painless and can go unnoticed; however, alter some days or weeks 50% of people bitten develop a characteristic ted 'lmil's eye'olike skin rash near the bite. Many experience flu-like ~ymploms ~ ff tho ~ttte Jitneysis uot su¢*~f.lly mt~l with the aPlnOPflate antibiotics (the spirochaete ~ em~ the b l ~ bmi~. while~ antibioticscannoO, more serious ImPlores can develop months or years later in around 10% of those infected. Such p~tients can be divided into two groups, according to the nature and ~verity of their , symptoms.Those with 'chronic Lyme disease often develop intermiUant arthritis followed by a monoarthritis, usually of the knog they can have neurological symptoms soeh as numbness, tinglingand weakness in the extremities; mood ch~ges, memory loss and headache; and sometimes also skin complaints. The bacterium cannot usually be isolated from either the synodal fluid or the eerebrospiual fluid (CSF), and aPCR test for borrelial DNAis not always positive in these fluids. However, appropriate antibiotic Ueatmentcan provide a e t ~ - strong evidence that persistent infwtion is a cause. Other patients are said to have 'post-Lyme- disease syndrome'; they have more diffuse symptoms, such as widespreadjoint and muscle pain; and they never show evidence of persisting bacteria. Man)' clinicians consider this diagnosis controversial because such symptoms could result from several diffe~'ent diseases. Others ~gae that the syndrome is the l~nlt of long-term neurologicaldamage cau~d by the acute infection, or persistent hmannological reaction/autoimmune attack or a hidden persistent infection (such as an intmcellular infection within the.brain). 'It's very controve~.xial whether or not these patients have persistent infection, and therefore whether they need antihioties,' says Arthur Weinstein (New York Medical College, Valhalla, NY, USA), who is recruiting some of the patienis in the u'iaL He adds that the ix)a-Lyme.disease syndrome patients do claim to feel belier during antibiotic therapy and worse whet: it stops, lBte clinical trial will anempt to clarify this controversy with US$ 4.2 million item the National Institute of Allergy and hd~ctkmsD ~ a ~ s (NIAJD: BeaMed, MD, USA). A team of ~e~areherm at ~everal imtimtions in noah/noahe~tem US& led by team leader Mink Klemlmer(New Fad#trodMedical Center, Boston, MA, USA), will recruit i l0 such patterns with a documented episode of acute Lyme disease who are seropositive for specific antibodies against Borrelia. Trial subjects must have had at least six months of post-Lym¢-disca~ symptoms, whatevertreatment was given for the initial presentingcomplaint.One group will receive intravenous ceftriaxone for one month, followed by oral doxycyclin¢for t~o months the other group will receive placebos. All subjects will have physical, neurological and psychological examinations at 0, 3 and 6 months into the trial, Weinstein's and Klempt~r's teams will he taking samplesof the trial subjects' CSF and performing neuroeognitivetests to investigate possible biochemical markers of the syudrome's neurological and behavioural effects. Weinstein believes that, underlyingpost-Lymedisease syndrome, there could be an abnormality in pain processing,perhapsresulting from a eanlrai nervous system dysfunction triggered by Lyme disease. Copyright ©1996 Elsevier Science Ltd. All rights reserved. 1357 - 43101961515.00 i~:~ om "<~ccess wilh ~+ep[accme'-tt ~.!o~e ~b, cr: ~ "One of ~t~e fimdameneai probiems o+geae ~ ~:~p:~ i~ i~a¢ ~be e~icienc3 of gone transfer is i . ' , ~>.: ~avs. but in Rmconi's anaemia "the cct~sc~:+=_+ ~i:'..g abnormal genes do not grey, well in the m:~ ~. ~ Therefore e~en occasioneds~emceffs t~¢ief .f" zhe norm~ gone have-,an a&antage over~he sm'rou..~,dirg diseased cells." Dok',dadds Nat gone therap} could ultimately offer a number of advm~tagesover cord blood for this tbnn of anaemia because there m'e no risks of complications from GvHD and pa~iep~ts do no~ need any preparato U chemotherapy Janet Fricker Lyme disease is con~dered by some in the USA to be a very 'sought-afterdiagnosis' because of its asmciafionwith an affluent na+al lifestyle. However, in those areas with the highest incidence, the t h a t of this dbea~.e can severely limit ~uch lifesPyles, Pe~sare given away, children m'e "~1~indoors, people have stopped walking or gardening and property values have fallen. For these reason~ and others, a vaccine again,~tLyme di~a~ is eagerly awaited. Both Commaght[a~ratorie~ Inc. s ++ ' [~ (S~ fftwa!cr, PA, USA) and Sm~lhg me Rce~:h+mt (~i~}p,hia; PA, USA)~ ¢~cting effigy studies of tMir vaccine+, which u~ a recombinant form of a SUrface protein S~ific to B. burgdorferi, ca!led OspA, as the immu~gen+ John ~ r a d n i k at Cmtnau~!t rays that t~i~ vaccine ~arm to be unusual~ause, whi~ most vacci~s prevent disea~, the~ ~s to help prevent infection itself,~ t h i n ~ tick, before the organisms are released into the host's bi~Urcam, rite spirochaeteis killed by antibodies in the ingeacd blood a+ the tick feeds. Sally CuRer, whose team at the C ~ n g Cross Hospital (London, UK) provkks the major diagnostic service for Lyme ~ in the UK, points oat that the nature of the ~ g e n e s i s of the acute disease is still unknown and ~ i y this baste understandinge ~ shed light on the exjstene¢ of pe,t ~ sy~romes. Even ff the trial were to prove that anfib~es are eff~ve, researchers must demonstra~ the k~ation tff persistence of tbe spirochaete to prove that llte infection persists and contributes to symptoms. Chdw O'Brlen a 407

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DNA polymoq~hic ,nm'kers In this case. becanse the donor was female. "all we had to do ~as h+ok at calls to see if they can'ied ma~e or i)malc chmmos~mes," explains Dr Paul Veys i Consuhant in Paediatric Bone Man'ow Tnmsphnts. GOS }

l;atare uses for cord blood cells fl:dudc their use as vehicles for gone therapy in child+on with immunedeficiencies, ntetabolic diseases and conditions such an thalassaemia and sickle cell disease. But Veys believes that related-donor cord blood transplants will not prove such a viable option fur treating patients with leukaemia because the so-called graft-versus-leukaemia effect, which is useful in these situations, might

be rcd|~ccd when a~smg n~atcbed-co~d ce]],~ as opposed to bo~lc +1~ar|o¢, cdls .

A Phase l pih,t s~{~dy, c+.aTenfly trader way at ihc N,ai¢u.+ai 1+~qitmes of Health ~Bet~tesda. MD t !SA }. is ]n the process of administering gone dxcrap3 ~o three patict~s with group C Fancon]'~ anaemia. The s~ady, led by Johnson Liu. involves using a relrovinfi vector to h~u-mduce the nomrd form of the gene into stem cells derived from autologous peripheral b~ood. Dr lnderjeet Dokai ¢Consuhant Paediatric Haematologist, The Hammersmith Hospital London, UKI has recruited a patient for this s~.~dy, and believe,~ that certain t~a~ures of Fanconi's anaemia compared with other diseases

The long-term finical effects of Lyme disease are under investigation in the USA in a double-blind, randomized, placebo-controlled trial of antibiotic treatment for patients with post-Lyme+disease syndrome.

Lyme disease ~ u r s in temperate regions worldwide and results from infection by the spirochaete bacterium Bormlia burgdorfe~i. This nficroorganism is carried and spread by infected ticks that feed on humans, dogs, deer and mice; their habitats include grass, shrubs and woodland. The incidence of the disease is particularly high in northeastern USA (up to 45 cases per 100 060 people per year) whereas in Europe there are only 1.4 ea~s and in the UK only 0.14 per ! ~ @10.

Tick bites am painless and can go unnoticed; however, alter some days or weeks 50% of people bitten develop a characteristic ted 'lmil's eye'olike skin rash near the bite. Many experience flu-like ~ymploms ~ ff tho ~ttte Jitneys is uot su¢*~f.lly m t ~ l with the aPlnOPflate antibiotics (the spirochaete ~ em~ the b l ~ bmi~. while ~ antibiotics cannoO, more serious ImPlores can develop months or years later in around 10% of those infected.

Such p~tients can be divided into two groups, according to the nature and ~verity of their , symptoms. Those with 'chronic Lyme disease often develop intermiUant arthritis followed by a monoarthritis, usually of the knog they can have neurological symptoms soeh as numbness, tingling and weakness in the extremities; mood ch~ges, memory loss and headache; and sometimes also skin complaints. The bacterium cannot usually be isolated from either the synodal fluid or the eerebrospiual fluid (CSF), and aPCR test for borrelial DNAis not always positive in these fluids. However, appropriate antibiotic Ueatment can provide a e t ~ - strong evidence that persistent infwtion is a cause.

Other patients are said to have 'post-Lyme- disease syndrome'; they have more diffuse symptoms, such as widespread joint and muscle pain; and they never show evidence of persisting

bacteria. Man)' clinicians consider this diagnosis controversial because such symptoms could result from several diffe~'ent diseases. Others ~gae that the syndrome is the l~nlt of long-term neurological damage cau~d by the acute infection, or persistent hmannological reaction/autoimmune attack or a hidden persistent infection (such as an intmcellular infection within the. brain). 'It's very controve~.xial whether or not these patients have persistent infection, and therefore whether they need antihioties,' says Arthur Weinstein (New York Medical College, Valhalla, NY, USA), who is recruiting some of the patienis in the u'iaL He adds that the ix)a-Lyme.disease syndrome patients do claim to feel belier during antibiotic therapy and worse whet: it stops, lBte clinical trial will anempt to clarify this controversy with US$ 4.2 million item the National Institute of Allergy and hd~ctkms D~a~s (NIAJD: BeaMed, MD, USA). A team of ~e~areherm at ~everal imtimtions in noah/noahe~tem US& led by team leader Mink Klemlmer (New Fad#trod Medical Center, Boston, MA, USA), will recruit i l0 such patterns with a documented episode of acute Lyme disease who are seropositive for specific antibodies against Borrelia. Trial subjects must have had at least six months of post-Lym¢-disca~ symptoms, whatever treatment was given for the initial presenting complaint. One group will receive intravenous ceftriaxone for one month, followed by oral doxycyclin¢ for t~o months the other group will receive placebos. All subjects will have physical, neurological and psychological examinations at 0, 3 and 6 months into the trial,

Weinstein's and Klempt~r's teams will he taking samples of the trial subjects' CSF and performing neuroeognitive tests to investigate possible biochemical markers of the syudrome's neurological and behavioural effects. Weinstein believes that, underlying post-Lymedisease syndrome, there could be an abnormality in pain processing, perhaps resulting from a eanlrai nervous system dysfunction triggered by Lyme disease.

Copyright ©1996 Elsevier Science Ltd. All rights reserved. 1357 - 43101961515.00

i~:~ om "<~ccess wilh ~+ep[accme'-tt ~.!o~e ~b, cr: ~ "One of ~t~e fimdameneai probiems o+ geae ~ ~:~p:~ i~ i~a¢ ~be e~icienc3 of gone transfer is i . ' , ~>.: ~avs. but in Rmconi's anaemia "the cct~s c~:+ =_+ ~i:'..g abnormal genes do not grey, well in the m:~ ~. ~ Therefore e~en occasioned s~em ceffs t~¢ief .f" zhe norm~ gone have -,an a&antage over ~he sm'rou..~,dirg diseased cells." Dok',d adds Nat gone therap} could ultimately offer a number of advm~tages over cord blood for this tbnn of anaemia because there m'e no risks of complications from GvHD and pa~iep~ts do no~ need any preparato U chemotherapy

Janet Fricker

Lyme disease is con~dered by some in the USA to be a very 'sought-after diagnosis' because of its asmciafion with an affluent na+al lifestyle. However, in those areas with the highest incidence, the t h a t of this dbea~.e can severely limit ~uch lifesPyles, Pe~s are given away, children m'e "~1~ indoors, people have stopped walking or gardening and property values have fallen. For these reason~ and others, a vaccine again,~t Lyme di~a~ is eagerly awaited. Both Commaght [a~ratorie~ Inc.

s ++ • ' [~ (S~ fftwa!cr, PA, USA) and Sm~lhg me Rce~:h+mt (~i~}p,hia; PA, USA)~ ¢ ~ c t i n g eff igy studies of tMir vaccine+, which u~ a recombinant form of a SUrface protein S~ific to B. burgdorferi, ca!led OspA, as the immu~gen+ John ~radnik at Cmtnau~!t rays that t~i~ vaccine ~ a r m to be unusual ~ause , whi~ most vacci~s prevent disea~, the~ ~ s to help prevent infection itself, ~thin ~ tick, before the organisms are released into the host's bi~Urcam, rite spirochaete is killed by antibodies in the ingeacd blood a+ the tick feeds.

Sally CuRer, whose team at the C ~ n g Cross Hospital (London, UK) provkks the major diagnostic service for Lyme ~ in the UK, points oat that the nature of the ~ g e n e s i s of the acute disease is still unknown and ~iy this baste understanding e ~ shed light on the exjstene¢ of pe, t ~ sy~romes. Even ff the trial were to prove that anfib~es are eff~ve, researchers must demonstra~ the k~ation t ff persistence of tbe spirochaete to prove that llte infection persists and contributes to symptoms.

Chdw O'Brlen

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