Pathological changes typical of Alzheimer's disease were significantly
reduced in mice by blockade of an immune system transmitter. A research
team from Charité -- Universitätsmedizin Berlin and the University of
Zurich has just published a new therapeutic approach in fighting
Alzheimer's disease in the current issue of Nature Medicine. This approach promises potential in prevention, as well as in cases where the disease has already set in.
Alzheimer's disease is one of the most common causes of dementia. In
Germany and Switzerland alone, around 1.5 million people are affected,
and forecasts predict a doubling of the number of patients worldwide
within the next 20 years. The accumulation of particular abnormal
proteins, including amyloid-ß (Aβ) among others, in patients' brains
plays a central role in this disease. Prof. Frank Heppner from the
Department of Neuropathology at Charité and his colleague Prof. Burkhard
Becher from the Institute for Experimental Immunology at the University
of Zurich were able to show that turning off particular cytokines
(immune system signal transmitters) reduced the Alzheimer's typical
amyloid-ß deposits in mice with the disease. As a result, the strongest
effects were demonstrated after reducing amyloid-ß by approximately 65
percent, when the immune molecule p40 was affected, which is a component
of the cytokines interleukin (IL)-12 and -23.
Relevant for human therapy
Follow-up experiments also relevant for humans showed that
substantial improvements in behavioral testing resulted when mice were
given the antibody blocking the immune molecule p40. This effect was
also achieved when the mice were already showing symptoms of the
disease. Based on the current study by Prof. Heppner's and Prof.
Becher's team, the level of p40 molecules is higher in Alzheimer's
patients' brain fluid, which is in agreement with a recently published
study by American colleagues demonstrating increased p40 levels in blood
plasma of subjects with Alzheimer's disease, thus showing obvious
relevance for human therapy.
The significance of the immune system in Alzheimer's research is the
focus of current efforts. Prof. Heppner and Prof. Becher suspect that
cytokines IL-12 and IL-23 themselves are not causative in the pathology,
and that the mechanism of the immune molecule p40 in Alzheimer's
requires additional clarification. However, they are convinced that the
results of their six-years of research work justify the step toward
clinical studies in humans, for which they plan to collaborate with a
suitable industrial partner.
IIn the context of other illnesses, such as psoriasis, a medication
that suppresses p40 in humans has already been applied. "Based on the
safety data in patients," comment Profs. Heppner and Becher, "clinical
studies could now be implemented without delay. Now, the goal is to
bring the new therapeutic approach to Alzheimer patients quickly."
Journal Reference:
- Johannes vom Berg, Stefan Prokop, Kelly R Miller, Juliane Obst, Roland E Kälin, Ileana Lopategui-Cabezas, Anja Wegner, Florian Mair, Carola G Schipke, Oliver Peters, York Winter, Burkhard Becher, Frank L Heppner. Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease–like pathology and cognitive decline. Nature Medicine, 2012; DOI: 10.1038/nm.2965
Courtesy: ScienceDaily
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