Need more research to clarify dimebolin affects
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In a surprising result, acute treatment with the drug dimebolin, currently in clinical development for Alzheimer's disease, increased excreted amyloid-β (Aβ) protein levels in a study presented at the 2009 International Conference on Alzheimer's Disease, held July 11 to 16 in Vienna, Austria.
Samuel Gandy, M.D., of Mount Sinai School of Medicine in New York City, and colleagues evaluated the molecular effects of dimebolin. The investigators used preclinical models, including cultured N2a mouse neuroblastoma cells overexpressing the SweAPP gene, isolated nerve terminals from transgenic TgCRND8 mice overexpressing the Swe/Indiana-APP gene, and freely moving Tg2576 transgenic mice overexpressing the SweAPP gene.
The researchers found that acute treatment with dimebolin increased the amount of Aβ levels released from the isolated nerve terminals of TgCRND8 mice. Interstitial fluid from dimebolin-treated Tg2576 mice also exhibited increased levels of Aβ protein. In contrast, the authors note, the media conditioned by dimebolin-treated SweAPP N2a cells showed either no difference or a decrease in the amount of Aβ protein. These results were consistent regardless of the preparation of dimebolin used (obtained from two independent vendors).
"This result is highly unexpected in what may prove to be a clinically beneficial Alzheimer's drug," Gandy said in a statement. "We need more research to further clarify how dimebolin affects Aβ levels in the brain." For example, chronic dimebolin treatment may have a different effect than observed with the acute treatment used in this study. ...http://www.modernmedicine.com
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Your Alzheimer's donation will help billions live without it. Donate online now
In a surprising result, acute treatment with the drug dimebolin, currently in clinical development for Alzheimer's disease, increased excreted amyloid-β (Aβ) protein levels in a study presented at the 2009 International Conference on Alzheimer's Disease, held July 11 to 16 in Vienna, Austria.
Samuel Gandy, M.D., of Mount Sinai School of Medicine in New York City, and colleagues evaluated the molecular effects of dimebolin. The investigators used preclinical models, including cultured N2a mouse neuroblastoma cells overexpressing the SweAPP gene, isolated nerve terminals from transgenic TgCRND8 mice overexpressing the Swe/Indiana-APP gene, and freely moving Tg2576 transgenic mice overexpressing the SweAPP gene.
The researchers found that acute treatment with dimebolin increased the amount of Aβ levels released from the isolated nerve terminals of TgCRND8 mice. Interstitial fluid from dimebolin-treated Tg2576 mice also exhibited increased levels of Aβ protein. In contrast, the authors note, the media conditioned by dimebolin-treated SweAPP N2a cells showed either no difference or a decrease in the amount of Aβ protein. These results were consistent regardless of the preparation of dimebolin used (obtained from two independent vendors).
"This result is highly unexpected in what may prove to be a clinically beneficial Alzheimer's drug," Gandy said in a statement. "We need more research to further clarify how dimebolin affects Aβ levels in the brain." For example, chronic dimebolin treatment may have a different effect than observed with the acute treatment used in this study. ...http://www.modernmedicine.com
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