Why Dementia Drugs Work in Lab but Not in Humans

By Rick Nauert PhD Senior News Editor Reviewed by John M. Grohol, Psy.D. on December 9, 2013

Researchers have been on a fast-track to develop drugs to slow or prevent Alzheimers disease. And whilemany of the new compounds appear to work well in animal and cell models, they have all failed in human clinical trials.

In a new study, reported online in the journal Stem Cell Reports, researchers provide interesting clues on the failures.

In the article, experts suggest why non-steroidal anti-inflammatory drugs (NSAIDs) which have successfully treated molecular signs of Alzheimers disease in cell and animal models eventually failed in clinical studies.

They discovered that although the compounds worked in non-neuronal cells lines typically used in pharmaceutical drug screening, human neurons are resistant to this class of drugs.

The results of our study are significant for future drug development approaches, because they imply that compound screening and validation studies might be much more reliable if they are conducted using the human cell type affected by the disease in question, said Oliver Brstle who senior-authored the study with colleague Philipp Koch, M.D.

Alzheimers disease is the most common cause of dementia among older people, yet there currently are no effective drugs to stop, slow or prevent disease progression.

Alzheimersis characterized by the accumulation of compounds called A peptides in the brain, and this process is believed to cause progressive neurodegeneration and dementia.

Longer A42 peptides tend to aggregate more than shorter A40 peptides, and a high ratio of A42 to A40 is used as a biomarker of Alzheimers disease.

NSAIDs have been found to restrain A processing, resulting in decreased A42/40 ratios in several cell and animal models of the disease.

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Why Dementia Drugs Work in Lab but Not in Humans