Amyloid-targeted therapeutics in Alzheimer's disease: use of human albumin in plasma exchange as a novel approach for Abeta mobilization.
A clinical investigation program was carried out to replace endogenous albumin of patients with mild to moderate Alzheimer's disease (AD) with 5% Human Albumin Grifols(R) through a plasma exchange (PE) schedule, in order to alter the dynamic equilibrium between albumin-bound Abeta in plasma and Abeta in cerebrospinal fluid. In a pilot proof-of-concept study, 7 patients underwent 6 PE in 3 weeks and 1 year of follow-up. Plasma Abeta determinations demonstrated a variation pattern in levels in relation with the PEs. Cognitive status scores (MMSE and ADAS-Cog) were more stable than expected. In a phase II clinical trial, 29 patients were randomized into PEtreated and control groups with 1 year follow-up. Interim results point toward the occurrence of Abeta40 mobilization in the PE-treated patients, who scored better in cognitive tests (differences at 9 months: 2.5 in MMSE and 5.5 in ADAS-cog). These results suggest that a PE program with 5% Human Albumin Grifols may have a promising role in the treatment of mild to moderate AD.
Boada
Mercè
M
ACE Foundation, Catalan Institute of Applied Neurosciences and the Neurology Service, University General Hospital Vall d'Hebron, Barcelona, Spain. mboada@fundacioace.com
Ortiz
Pilar
P
Anaya
Fernando
F
Hernández
Isabel
I
Muñoz
Joan
J
Núñez
Laura
L
Olazarán
Javier
J
Roca
Isabel
I
Cuberas
Gemma
G
Tárraga
Lluís
L
Buendia
Mar
M
Pla
Ramón P
RP
Ferrer
Isidre
I
Páez
Antonio
A
D000544:Alzheimer Disease / Q000503:physiopathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000209:etiology / Q000628:therapy; D016503:Drug Delivery Systems; D006801:Humans; D010951:Plasma Exchange / Q000379:methods*; D012709:Serum Albumin / Q000008:administration & dosage* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D012709:Serum Albumin