Shirvan A, Reshef A, Yogev-Falach M, Ziv I.
Exp Neurol. 2009 Sep;219(1):274-83. Epub 2009 Jun 3.
Aposense Ltd., 5 Ha'Odem St., P.O. Box 7119, Petach-Tikva, 49170, Israel.
Current pre-mortem diagnosis of neurodegenerative disorders such as
Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS) is based on
clinical assessment of neurological deficits. However, symptoms and signs
emerge only late in the disease course, thus indicating an urgent need for
novel tools for detection of the underlying neuropathology. NST-729 (MW=310)
is a novel molecular imaging probe, which is a member of the ApoSense family
of small molecule detectors of apoptosis. We now report on the ability of
NST-729, upon its systemic administration in vivo, to detect characteristic
neuropathology in pre-clinical models of AD (Tg2576 transgenic mice) and ALS
(transgenic SOD-1 G93A mutation mice). In the AD model, NST-729 clearly and
selectively bound and imaged amyloid plaques, in excellent correlation with
a typical amyloid ex vivo staining (Congo red). In the ALS model, NST-729
distinctly and selectively imaged multiple degenerating neurons in the motor
nuclei in the pons, medulla and spinal cord, manifesting numerous multifocal
irregularities and disruptions of neuritic projections, typical of axonal
apoptosis. Study results therefore support the potential utility of NST-729
as a cross-disease biomarker for neurodegeneration, and also its potential
role as the first molecular probe for ALS. Future radio-labeled NST-729
analogues may assist in the early diagnosis of disease, and in the
development of neuroprotective therapies for these severe neurological
disorders.
PMID: 19500576 [PubMed - indexed for MEDLINE]
