20 luglio 2015

articolo postato il: 2015-07-20 23:48:33

Pubblicato sul New England J. of Medicine il primo studio clinico sull`efficacia di un anticorpo monoclonale anti SAP nell`indurre il riassorbimento dei depositi amiloidi.

I risultati sono molto incoraggianti e la procedura apre una prospettiva completamente nuova nella cura delle amiloidosi sistemiche. Se questo approccio terapeutico si rivelerà efficace anche nelle amiloidosi cardiache, la storia clinica della malattia cambierà radicalmente.


N Engl J Med. 2015 Jul 15.

Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component.

Richards DBCookson LMBerges ACBarton SVLane TRitter JMFontana MMoon JCPinzani MGillmore JDHawkins PNPepys MB.



Background The amyloid fibril deposits that cause systemic amyloidosis always contain the nonfibrillar normal plasma protein, serum amyloid P component (SAP). The drug (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC) efficiently depletes SAP from the plasma but leaves some SAP in amyloid deposits that can be specifically targeted by therapeutic IgG anti-SAP antibodies. In murine amyloid A type amyloidosis, the binding of these antibodies to the residual SAP in amyloid deposits activates complement and triggers the rapid clearance of amyloid by macrophage-derived multinucleated giant cells. Methods We conducted an open-label, single-dose-escalation, phase 1 trial involving 15 patients with systemic amyloidosis. After first using CPHPC to deplete circulating SAP, we infused a fully humanized monoclonal IgG1 anti-SAP antibody. Patients with clinical evidence of cardiac involvement were not included for safety reasons. Organ function, inflammatory markers, and amyloid load were monitored. Results There were no serious adverse events. Infusion reactions occurred in some of the initial recipients of larger doses of antibody; reactions were reduced by slowing the infusion rate for later patients. At 6 weeks, patients who had received a sufficient dose of antibody in relation to their amyloid load had decreased liver stiffness, as measured with the use of transient elastography. These patients also had improvements in liver function in association with a substantial reduction in hepatic amyloid load, as shown by means of SAP scintigraphy and measurement of extracellular volume by magnetic resonance imaging. A reduction in kidney amyloid load and shrinkage of an amyloid-laden lymph node were also observed. Conclusions Treatment with CPHPC followed by an anti-SAP antibody safely triggered clearance of amyloid deposits from the liver and some other tissues. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT01777243).