Developing medicines is like doing a puzzle. You stare at it and gamble. Then you test it and if you are lucky you succeed. We were lucky.
Manhasset, NY (Vocus) June 23, 2008
Yousef Al-Abed, PhD, designs medicines like an artful tailor, stitching pieces of molecules together to create novel compounds that may ultimately save lives. And his latest work has paid off in laboratory studies that could pay major dividends in staving off Alzheimer’s disease.
Dr. Al-Abed, head of medicinal chemistry at The Feinstein Institute for Medical Research, was looking for a way to target the amyloid plaques that clump together in between neurons in the brains of people with Alzheimer’s. Amyloid is a normal brain substance that can take on a toxic life of its own when something goes wrong in the machinery of the brain. The amyloid gets sticky and begins to accumulate and this sets in motion a number of events, including killing nearby neurons that are involved with holding decades of memories – and not just of special moments but also the important details of doing ordinary tasks of everyday living. Over time, Alzheimer’s robs people of their ability to remember how to get dressed, take care of themselves or even remember the loved ones that they have married or brought into the world.
Dr. Al-Abed looked at the assembly of amyloids in this toxic form and saw a way to change the molecular machinery so that a substance could drive the amyloid into a new form that does not aggregate to form plaques in the brain. The medicine he has tested is called CNI-1493 and studies in the laboratory have found that that it facilitates the clearance of amyloid (so it doesn’t clump) and it also neutralized the toxicity of the amyloid on its way to becoming a plaque.
In a study published this month in the Journal of Experimental Medicine, Dr. Al-Abed and his collaborators at Marburg University in Germany – Michael Bacher, PhD, and Richard Dodel, MD – found that laboratory models of Alzheimer’s were protected against the disease on several levels. In studies conducted in Germany, the animals were able to recognize novel objects that their littermates, without the drug on board, were no longer able to do. They also found that the amyloid burden in the brain was reduced by 70-85 percent in the areas hard hit in Alzheimer’s – the cortex and the hippocampus.
Dr. Al-Abed has evidence that the molecule changes the assembly of amyloid and protects against it forming plaques. The researchers also know that inflammation is a characteristic feature of amyloid deposition and found that microglial activation was virtually gone in the brains of the lab models. Microglial activation is a measure of inflammation in the brain. It also doesn’t interfere with the normal processing of amyloid.
“It’s very exciting,” said Dr. Al-Abed. “Developing medicines is like doing a puzzle. You stare at it and gamble. Then you test it and if you are lucky you succeed. We were lucky.”
CNI-1493 is made by Cytokine Pharmaoscience and is in early stages of clinical testing for Crohn’s disease. The Feinstein Institute for Medical Research owns a patent for its use in Alzheimer’s and Dr. Al-Abed is working with his German collaborators on the next step: The design of a clinical trial.
About The Feinstein Institute for Medical Research
Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in Parkinson's disease, Alzheimer’s disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, leukemia, lymphoma, neuroimmunology, and medicinal chemistry. The Feinstein Institute, part of the North Shore-LIJ Health System, ranks in the top 6th percentile of all National Institutes of Health grants awarded to research centers. For more information: http://www.FeinsteinInstitute.org or http://www.feinsteininstitute.typepad.com.
Contact: Jamie Talan, science writer-in-residence
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