An anti-inflammatory drug in clinical trials as a Crohn’s disease treatment has shown therapeutic promise in a mouse model of Alzheimer disease. The benefits of CNI-1493, an inhibitor of p38 mitogen-activated protein kinase, were first reported in March at Keystone Symposia’s meeting on Alzheimer’s disease held in Keystone, Colorado (see ARF related news story). In press at the time of our meeting coverage, the findings were published this week in the Journal of Experimental Medicine.

Led by Yousef Al-Abed, head of medicinal chemistry at the Feinstein Institute for Medical Research, Manhasset, New York, the researchers first showed that CNI-1493 disrupts in vitro Aβ oligomer formation and protects cultured neuronal cells from the toxic effect of soluble Aβ oligomers. In CRND8 transgenic mice overexpressing human APP, an eight-week course of CNI-1493 reduced amyloid plaque area in the cortex by 70 percent, and in the hippocampus, by 87 percent. Treatment with CNI-1493 did not affect spatial memory but did preserve the mice’s object recognition memory. Compared with placebo animals, treated mice also had reduced microglial activation, measured by expression of the microglial surface protein F4/80.

According to a Feinstein Institute press release, Al-Abed is working with lead author Michael Bacher of Philipps University in Marburg, Germany, and other German collaborators to design the first clinical trial of CNI-1493 as an AD drug.—Esther Landhuis

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References

News Citations

  1. Keystone Drug News: Repurposing the Anti-Inflammatory Drug CNI-1493?

Other Citations

  1. CRND8 transgenic mice

External Citations

  1. clinical trials

Further Reading

Primary Papers

  1. . CNI-1493 inhibits Abeta production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease. J Exp Med. 2008 Jul 7;205(7):1593-9. PubMed.