Pipeline
Behandling ud over glutenfri kost
Flere tilgange er nået til randomiserede forsøg. Ingen har erstattet diæten, og feltet har en lang historie med lovende resultater, som ikke holdt.
Hvorfor et lægemiddel er svært
Cøliaki har en usædvanlig egenskab blandt autoimmune sygdomme: udløseren er kendt og kan fjernes. Det sætter en meget høj standard — ethvert lægemiddel skal være sikrere og mere praktisk end simpelthen ikke at spise gluten, i en population, der ikke er akut syg, når den er behandlet. Det betyder også, at det realistiske mål ikke er "at spise brød igen", men "at være beskyttet, når restauranten begår en fejl".
Transglutaminase 2-hæmning
Vævstransglutaminase modificerer glutenpeptider på en måde, der gør dem langt mere immunogene — det er enzymet i centrum af sygdomsmekanismen og målet for det antistof, der bruges til at diagnosticere den. At blokere det er derfor mekanistisk elegant. Et randomiseret forsøg med en TG2-hæmmer rapporterede dæmpning af gluteninduceret slimhindeskade under udfordring [5], hvilket er det mest opmuntrende enkeltresultat, feltet har produceret.
TG2-hæmning
Enzymatisk nedbrydning
Glutenaser sigter mod at nedbryde gluten i maven, før det når tyndtarmen. Det tekniske problem er alvoren: for at beskytte mod et normalt hvedemåltid skal et enzym nedbryde gram af protein i et fjendtligt, surt miljø inden for et kort tidsvindue. Flere kandidater har vist aktivitet mod små mængder uden at påvise beskyttelse mod realistisk eksponering. Arbejde med probiotiske præparater med in vivo glutennedbrydende aktivitet illustrerer tilgangen.
Probiotika
Der findes et systematisk review og meta-analyse af randomiserede kontrollerede forsøg med probiotika til cøliaki, og det støtter ikke rutinemæssig brug. Mikrobiomforskelle ved cøliaki er reelle og reproducerbare, men at modificere dem har ikke ført til klinisk gavn.
Andre retninger
- Induktion af immuntolerance. Peptidbaserede tilgange, der sigter mod at omtræne immunresponset, konceptuelt svarende til allergen-immunterapi.
- Modulation af tight junctions. Reduktion af tarmens permeabilitet, så færre glutenpeptider passerer igennem. Forsøgene har givet blandede resultater.
- Cytokinblokade. Rettet mod refraktær sygdom snarere end mod almindelig cøliaki [7].
- Vaccination. Diskuteret i lang tid, gentagne gange forsinket og ikke tæt på.
Hvad kan man forvente
Det plausible næste skridt er et supplement, der reducerer konsekvenserne af utilsigtet eksponering for mennesker, der allerede er strikte. Det ville være reelt værdifuldt — utilsigtet eksponering er almindelig, som forskning i kontaminering viser — uden at være den frihed, medieomtalen har tendens til at love.
Ofte stillede spørgsmål
Vil der komme en pille, der lader mig spise brød?
Skal jeg tage et glutenfordøjende enzym?
Er det værd at prøve probiotika?
Hvordan kan jeg deltage i et forsøg?
References
Every citation below links to the original peer-reviewed record on PubMed or via DOI. Nothing here is a substitute for medical advice.
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