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Alzheimer-Therapie: Bisher schlugen alle
Versuche fehl, den Verlauf einer Alzheimer-Erkrankung
mit Hilfe von Medikamenten signifikant zu verbessern.
Daher hat die hier vorgestellte Studie eine große
Bedeutung. Unter der Gabe 2 x täglich von 800
mg Tarenflurbil gelang es bei den in die Studie
eingeschlossenen Alzheimer-Patienten im Vergleich
zu einem Scheinmedikament ein Fortschreiten der
den Alltag beeinflussenden neurologischen Ausfälle
zu verlangsamen.
Die vollständige englischsprachige
Kurzversion dieser Studie (sog. MEDLINE
Abstract) finden Sie
hier
Wilcock GK,
et al.
Efficacy
and safety of tarenflurbil in mild to moderate
Alzheimer`s disease: a randomised phase II trial.
Lancet
Neurol. 2008 Jun;7(6):483-93.
Epub 2008
Apr 29. PMID: 18450517
Abstract
BACKGROUND: The amyloid-beta peptide
Abeta(42) has been implicated in the
pathogenesis of Alzheimer`s disease (AD). We
aimed to test the effects of tarenflurbil, a
selective Abeta(42)-lowering agent (SALA), on
cognition and function in patients with mild to
moderate AD.
METHODS:
210 patients living in the community who had a
mini-mental state examination (MMSE) score of
15-26 were randomly assigned to receive
tarenflurbil twice per day (400 mg [n=69] or 800
mg [n=70]) or placebo (n=71) for 12 months in a
phase II, multicentre, double-blind study.
FINDINGS:
A prespecified interaction analysis revealed
that patients with mild AD (baseline MMSE 20-26)
and moderate AD (baseline MMSE 15-19) responded
differently to tarenflurbil in the ADAS-cog and
the ADCS-ADL (p>or=0.10); therefore, these
groups were analysed separately.
Patients
with mild AD in the 800 mg tarenflurbil group
had lower rates of decline than did those in the
placebo group in activities of daily living
(ADCS-ADL
difference in slope 3.98 [95% CI 0.33 to 7.62]
points per year, effect size [reduction from
placebo decline rate] 46.4%, Cohen`s d 0.45;
p=0.033) and global function (CDR-sb difference
-0.80 [-1.57 to -0.03] points per year, effect
size 35.7%, Cohen`s d 0.42; p=0.042); slowing of
cognitive decline did not differ significantly (ADAS-cog
difference -1.36 [-4.07 to 1.36] points per year,
effect size 33.7%, Cohen`s d 0.20; p=0.327). In
patients with moderate AD, 800 mg tarenflurbil
twice per day had no significant effects on
ADCS-ADL and ADAS-cog and had a negative effect
on CDR-sb (-52%, Cohen`s d -1.08; p=0.003).
The most
common adverse events were diarrhoea (in seven,
nine, and five patients in the 800 mg, 400 mg,
and placebo groups, respectively), nausea (in
seven, seven, and four patients), and dizziness
(in five, nine, and four patients). Patients
with mild AD who were in the 800 mg tarenflurbil
group for 24 months had lower rates of decline
for all three primary outcomes than did patients
who were in the placebo group for months 0-12
and a tarenflurbil group for months 12-24 (all
p<0.001), and had better outcomes than did
patients who were in the placebo group for
months 0-12 and the 800 mg tarenflurbil group
for months 12-24 (all p<0.05).
INTERPRETATION: 800 mg tarenflurbil twice
per day was well tolerated for up to 24 months
of treatment, with evidence of a dose-related
effect on measures of daily activities and
global function in patients with mild AD.
FUNDING: Myriad Pharmaceuticals.
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