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THE LANCET Neurology Vol 1 December 2002 http://neurology.thelancet.com468

A 10 year study of 107 boys with X-linked adrenoleukodystrophy (ALD)has shown that Lorenzo’s oil has somevalue as a preventive treatment. HugoMoser (Kennedy Krieger Institute,Baltimore, MA, USA), who presentedhis group’s results at the InternationalSymposium on Peroxisomal Disordersand Regulations of Genes (GhentUniversity, Belgium, Sept 25–28, 2002),reports that “continuous treatment withLorenzo’s oil brought about significantreductions in the levels of very longchain fatty acids (VLCFAs) thatcorrelated with a reduced risk ofdeveloping neurological abnormalities”.

Lorenzo’s oil was developed byAugusto and Michaela Odone aftertheir son Lorenzo started to exhibitsymptoms of ALD in the mid 1980s:their story was portrayed in the 1993 film“Lorenzo’s oil”. Lorenzo himself startedthe therapy after his symptoms appearedand, today, has only limited movementand needs 24 h care. Augusto Odone(The Myelin Project, Dunn Loring, VA,USA) is delighted with the study, sayingthat he is “very happy that this scientificstudy has finally shown that Lorenzo’s oilis able to help many children avoid theeffects of ALD”.

Moser and colleagues followed 69patients with ALD in the US and 26 inEurope. All had a mutation in theABCD1 gene but were symptom-free andhad normal MRI scans. Plasma levels ofVLCFAs were monitored between threeand six times a year and neurologicaltests and MRI scans were done annually:the current average follow-up is 3 years.“There was a 77% reduction in risk ofdeveloping neurological abnormalities,and a 65% reduction in risk ofdeveloping structural abnormalitiesdetectable by MRI in both groups”,explains Moser. Moser now recom-mends that “boys with ALD who areneurologically normal and have a normalMRI and who are between 18 monthsand 6 years old be given Lorenzo’s oilalong with a carefully supervised diet,under the direct supervision of amultidisciplinary team”.

Alan Percy (University of Alabama,Birmingham, Alabama, USA) agrees that“while Lorenzo’s oil is certainly not acure, in the absence of any significant

side-effects, it certainly merits con-sideration as a treatment strategy wheninstituted early”. Johannes Berger (BrainResearch Institute, Vienna, Austria) alsowelcomes the results and agrees thatcontinued follow-up of the patients isnecessary. Since the treatment did notprevent the appearance of abnormalitiesin all ALD patients, Berger also warnsthat “it will be important to establishwhether those participants who currently

remain healthy continue to escape thesevere cerebral inflammatory formcharacteristic of the childhood disease”.

Moser stresses that all boys in thestudy have been monitored rigorouslyfor early indications of brain abnor-malities on MRI scans because thesepatients are good candidates for a bonemarrow transplant (BMT). PatrickAubourg (Hopital St Vincent de Paul,Paris, France) and Elsa Shapiro(University of Minnesota, Mineapolis,MN, USA) have shown that BMT canhalt or even reverse some of the earlysymptoms of ALD (Lancet 2000; 356:713–18). Research is in progress to makethe procedure more effective, andrecently, Lolie Yu and colleagues at theChildren’s Hospital in New Orleans (LA,USA) published a case report ofsuccessful BMT in a boy with ALD forwhom CD34+ stem cell selection wasused to reduce the risk of graft-versus-host disease (Metab Brain Dis 2002; 17:139–42). “6 months post transplant, thetreatment seems to have beensuccessful”, reports Yu. Berger points outthat autologous BMT after gene therapyof endogenous hematopoietic stem cellsmay also be possible in the future.

The search for new ALDtreatments, particularly drugs, ishampered by a lack of knowledge ofthe mechanism that underlies ALD.The genetic defect occurs in ABCD1,which encodes a peroxisomal ATP-binding cassette transporter protein.Without a functional protein, betaoxidation of VLCFAs is reduced,allowing them to build up to abnormalconcentrations. “However, no one yetknows exactly how the gene defectleads to the biochemical changes, andto the disease symptoms,” says Moser.In October, Aurora Pujol (IGBMC,Strasbourg, France) presented resultsto the American Society of HumanGenetics annual meeting (Baltimore,MD, USA), showing that stableoverexpression of ALD related protein,another peroxisomal transporter thathas 88% homology with the proteinencoded by ABCD1 in ALD-deficientmice leads to full correction of C26:0and C24:0 fatty acids in the adrenalgland, the PNS, and the CNS. “Thisnormalisation of the biochemicalphenotype correlates with an improve-ment of the neurological abnormalitiesseen in the mouse model of ALD,making ABCD2, the gene that codes forALDRP, an interesting target for apharmacogenomic approach to ALDtreatment”, says Pujol.

On Sept 30, 2002, Moser attendeda meeting to discuss NIH funding ofmulticentre trials for ALD, where adecision was taken to press ahead withtherapeutic trials while continuingfundamental research. “As well ascontinuing the follow-up for thisstudy, we are now planning a study forQ10 in ALD, as possible mito-chondrial abnormalities have beenrecognised in association with thegene defect in ABCD1”, says Moser.He stresses that diagnosis remains thekey to enhancing survival and qualityof life in patients with ALD and hereports that the NIH is also funding afeasibility study for neonatal screeningfor ALD. “Our ultimate aim should beto identify all boys with ALD beforethey develop symptoms and to applytherapies that can prevent braindamage”, concludes Moser.Kathryn Senior

Lorenzo’s oil may help to prevent ALD symptoms

Newsdesk

Lorenzo Odone and Oumouri Hassane, May 2001

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