Dr. Martin Watterson, John G. Searle Professor of Molecular Biology and Biochemistry at Northwestern University Feinberg School of Medicine, is the lead author of research findings that offer a tremendous glimmer of hope for Alzheimer’s patients. He has announced the discovery of new molecules that work in a drug-like fashion to target brain enzymes that contribute to early memory loss in Alzheimer’s patients. These molecules, developed in the laboratory of Dr. Watterson, have been observed to not only halt memory deterioration but also to repair communication in the brain cells of mice.
Scientists note that changes in brain structure begin as much as ten to 15 years before the symptoms of memory loss are visible. Dr. Watterson hopes that in the future a new class of drugs can be developed from these enzymes that will be administered at sufficiently early stages, when nerve cells are just beginning to become damaged, and thereby halt certain aspects of memory loss in Alzheimer’s.
One of the causes of the brain inflammation and impaired neuron functioning that we see in Alzheimer’s is due to the enzyme p38 mitogen-activated protein kinase (p38MAPK) that becomes over-active in the brains of Alzheimer’s patients. This new drug-like molecule, named MW108, may inhibit the toxic impact of p38MAPK in the brain. In mice trials, researchers discovered that MW108 inhibited the release of inflammatory proteins, as well as served as a shield against the damaging effects of beta-amyloid. When injecting MW108 into mice before delivering beta-amyloid into their brains, the mice continued to perform well on memory and learning tests.
With such stunning results, researchers are optimistic over the possibilities of developing novel drug therapies that specifically target molecular processing in the brain. Additionally, scientists now have a new strategy for cultivating novel drug therapies that address other aspects of Alzheimer’s as well as other neurological diseases. Through funding from the National Institutes of Health, Dr. Watterson and his team will work to further stabilize MW108 so that researchers can safely move into phase 1 clinical trials on humans.
New findings by Virginia Commonwealth University (VCU) researchers implicate naturally occurring zinc as a causative agent in regulation of apoptosis. This is a significant development in the search for drug therapies to treat debilitating illnesses and diseases such as cancers, Parkinson’s and Alzheimer’s.
The VCU research findings were recently published in Angewandte Chemie, in its international edition. Apoptosis is the naturally occurring process of cell death. There are a number of enzymes that regulate the process of apoptosis. If there is a deficiency in one of the mechanisms regulating apoptosis, neurological diseases such as Alzheimer’s occur. It has been established that zinc inhibits caspase activity, thereby regulating apoptosis. Drug treatments in use today for cancer and Alzheimer’s target the caspases, therefore this new research could be key to the scientific discovery of new therapeutic agents.
Eleven caspases are identified today. Researchers focused their efforts on caspase-3, one of the seven caspases known to regulate apoptosis. Using established biophysical and enzymologic techniques, they discovered a heretofore unknown interaction between zinc and caspase-3. Nicholas P. Farrell, PhD. of the VCU Developmental Therapeutics program said that further study will need to be conducted, but it could be that zinc is interacting with all the caspases. If so, then the focus will be on developing drug therapies that would target this zinc-caspase interaction to regulate apoptosis.
In the meantime, the study is precipitating a new line of scientific inquiry, called bioinorganic chemistry of apoptosis, which is examining and seeking to understand how the requisite metal ions are interacting in the fundamental process of life and death of cells. Dr. Farrell noted that zinc’s role in constraining apoptosis is exactly the opposite of the metal closest to it—copper, which is known to accelerate apoptosis.
Dr. Michael Mullan is CEO of the Roskamp Institute, a Sarasota, Florida based research facility. The institute conducts research on Alzheimer’s disease and other neurodegenerative disorders, as well as traumatic brain injury aftermath and potential biological markers for substance abuse. Mullan specifically works in the Roskamp Memory Disorder Clinic, where he focuses on finding treatments, and hopefully a cure, for Alzheimer’s disease, which affects approximately 5 million Americans, mostly ages 60-80.
Mullan’s inspiration for studying Alzheimer’s
On one of his blogs, Michael Mullan discusses why he focuses on Alzheimer’s in his research. He points to the amazing history of many sufferers of the disease; they have long memories over the course of lives consisting of many interesting experiences, either in the military, in business or otherwise. One of the expressions of Alzheimer’s is that short term memory deteriorates, while older memories seem more present and clear. The tendency to nostalgia for Alzheimer’s patients, he believes, is fascinating; while the short-term memory loss causes agony for the patient, as well as their families. Mullan takes pride in the fact that he has the ability to offer these people a treatment for their disease. Although it is not yet a cure, his ability to offer FDA approved drugs and treatments, as well as experimental methods the Roskamp Institute is exploring, gives hope to many people who are suffering from their loved ones’ memory loss. Being able to give people hope in dealing with such a difficult disease, which affects the entire family, is one of Mullan’s main inspirations for continuing steadfastly in his research.
The Roskamp Institute is funded by its namesake, as well as the National Institutes of Health, the U.S. Department of Defense, the Veteran’s Administration and CTAC. Their research is not just into Alzheimer’s, however; the Memory Disorder Clinic also deals with post-trauma patients, especially those with head trauma. This is the reason for many military veterans participating in the institute’s research. Mullan and his partner, Dr. Fiona Crawford, lead a team aiming to develop therapeutic methods and specific targets to achieve a deeper understanding of Alzheimer’s and its etiology. Mullan’s team discovered a genetic error which causes an excessive production of beta-amaloid. The mutation is what forms the basis for Alzheimer’s disease; it proves that there is a genetic propensity for the disease and lead this research team to begin searching for a way of understanding its presentation. Not only is Mullan’s Roskamp team searching for potential treatments for Alzheimer’s; they hope to find a cure and potentially also find ways to treat and cure some types of cancer.
The medical training of Michael Mullan
Originally trained as a medical professional at the London University, Mullan has received many awards throughout his career. His first was the Ethel Williams Scholarship for postgraduate research; already at this early point in his career, he was focused on Alzheimer’s research, which he conducted also at the Royal Free Hospital. He also earned a PhD from London University, studying molecular genetics.