Researchers Uncover New Target for Alzheimer’s Disease Drugs

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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NilvadipineIn a recent study published in the online version of Journal of Biological Chemistry scientists reported to have found a new target molecule that will help the fight against Alzheimer’s disease. The study is entitled, “The Spleen Tyrosine Kinase (syk) Regulates Alzheimer’s Aβ Production and Tau Hyperphosphorylation”.

In this study, scientists at the Roskamp Institute, while trying to understand the mode of action of an anti-hypertensive drug – Nilvadipine – realized that this compound reduced amyloid protein accumulation, a key event in neurological disorders, such as Alzheimer’s disease. Additionally, the drug also ameliorated neuro inflammation and had a positive effect over the tau protein, another protein that together with amyloid causes damage and eventual death of nerve cells in the brain. The team performed further studies to understand which molecule was being targeted by the drug, and found it to be the SYK protein.

Daniel Paris, Ph.D., neurobiologist and study lead author, noted, “These studies suggest there is a single drug target to inhibit all the three key pathologies of Alzheimer’s disease.”

Michael Mullan, M.D., Ph.D., study leading author added, “Our studies have revealed that the spleen tyrosine kinase (SYK) enzyme is at a crossroad from which all three of the brain abnormalities known to be associated with Alzheimer’s disease diverge. Hopefully, academic or industry researchers can now develop new drugs to inhibit SYK which are suitable for clinical trials in Alzheimer’s disease.”

The authors performed further studies, and Dr. Paris showed that by blocking SYK activity, this protein is responsible for the three hallmarks of Alzheimer’s disease — inflammation, accumulation of amyloid protein, and modulation of the ‘tau‘ protein.

Thus, Dr. Paris commented, “The potential for developing a single “multi-modal” drug treatment that will control all three of these Alzheimer’s characteristics has us very excited. All of these pathologies are interrelated. In theory, by interrupting these three molecular pathways, we can develop more effective drugs to stop the disease. To date, all the drugs that have been tested to only attack one pathology, or Alzheimer’s characteristic, at a time. What is needed is one drug to address all three.”

Now, the team at the Roskamp Institute is seeking to translate their results into the clinic by developing new drugs, possibly with partnerships in academic and industry-based groups. Accordingly, a Phase III clinical trial of Nilvadipine for Alzheimer’s disease is currently underway in Europe.

Dr. Fiona Crawford, CEO of the Roskamp Institute commented, “We didn’t know, until now, that SYK was a possible therapeutic target for Alzheimer’s disease. We’d be delighted for anyone to come up with an “anti-SYK” treatment to stop Alzheimer’s.”

David H. Cribbs, Ph.D., Research Professor at University of California Irvine (UCI), Associate Director of the Institute for Memory Impairment and Neurological Disorders, and Co-Leader of the UCI Alzheimer’s Disease Research Center Neuropathology Core, also commented, “These findings are really significant. With all the failures of the clinical trials of drugs for this dementia up to this point, the finding of new therapeutics is wonderful. And Nilvadipine has a good safety profile.”