Rutgers neuroscientists are exploring promising new treatments for Alzheimer's, in part by addressing less-researched aspects of the disease.
Among Jacqueline Krieger Klein’s many attributes, a sharp intellect and passion perhaps stood out among the others. Her son, Roger Klein, remembers sitting at the dinner table with her, waiting for his father to arrive home from work. “There were discussions about all kinds of things—politics, public policy, the community,” says Roger, an attorney-turned-investor. “When my mother asked me a question, she didn’t want a yes-or-no answer. She made me think about the reasoning behind it. She was like a law professor!”
As the wife of U.S. congressman and Rutgers alumnus Herbert Klein, Jackie did more than talk the talk. “She and my father always valued community engagement,” says Roger. In addition to earning her MBA, working as an accountant, and raising a family, Jackie poured her energy into nonprofits, especially children’s and religious charities, around Clifton, New Jersey. “She was very social, very networked, and very friendly.”
In 2008, at age 78, Jackie began to lose her ability to engage with the world as Alzheimer’s disease symptoms slowly emerged. Because she was so adept at conversation, the family at first didn’t detect the change. “It was sad to watch her world gradually decline,” Roger says. Nine years later, the disease robbed the world of her.
The Kleins’ story of life, love, and loss is too common. Alzheimer’s disease or dementia affects an estimated 6 million Americans, a figure that is growing. Experts predict that in five years, nearly 1 million people in the tristate region of New York, New Jersey, and Pennsylvania will have some form of dementia.
“Alzheimer’s disease is one of the world’s largest problems—and a growing problem,” says Brian Strom, chancellor of Rutgers Biomedical and Health Sciences (RBHS). “Yet, there are very few treatments, and they are not very effective.”
Though more than 100 drugs have been tested for treating Alzheimer’s disease, the U.S. Food and Drug Administration has approved only four of them. Today, the neuroscientists at the Rutgers Brain Health Institute, part of RBHS, are working to change that by looking at Alzheimer’s disease from a fresh perspective.
Recently, they have identified several medications and test procedures that are showing promising results. However, the journey from lab to patient can be a long one. Rutgers’ leadership realized that to bring discoveries from “bench to bedside” more quickly, finding a means to conduct human clinical trials on campus would be necessary. Thanks to a donation from Herbert Klein RC’51 and his family, the ambitious effort is underway.
"My wife was a wonderful woman whose life was cut down by this dreadful disease. Sadly, nothing could really be done for her,” says Klein. “We’re hoping that the new ideas being developed at Rutgers will make the university a leader in the fight to defeat it.”
Alzheimer’s researchers have been stuck, in large part, since the discovery of the disease. On November 3, 1906, during the autopsy of a patient with “profound memory loss,” German physician Alois Alzheimer noticed brain abnormalities, now known as plaques and tangles. Both result from the abnormal buildup of proteins. Plaques are clumps of beta-amyloid protein, which form in the spaces between neurons, and tangles are fibrous structures made of tau protein that accumulate within brain cells. Neuroscientists have long believed that the key to treating Alzheimer’s disease lay in reducing the buildup of the proteins—the focus of most research. Unfortunately, even medications that broke down the clumps and tangles did not ease patients’ symptoms.
“Drug companies have spent billions of dollars developing medicines for Alzheimer’s disease, but they haven’t been successful,” says Gary Aston-Jones, director of the Brain Health Institute. That’s why, shortly after he joined Rutgers in 2014, Aston-Jones established a focus within the Brain Health Institute to study Alzheimer’s disease and, with a gift from Klein, was able to hire Luciano D’Adamio as the Jacqueline and Herbert Klein Endowed Chair for Alzheimer’s Disease Research. Soon after, with additional support from Klein, Aston-Jones hired Hyung Jin Ahn to serve as a junior faculty member in this effort. They have put their innovative, nondogmatic approaches to the test, with encouraging results.
Because of the limited success in the reduction of plaques and tangles, D’Adamio is addressing their formation instead. He has identified biological pathways (chain reactions inside cells) that are causing the proteins to accumulate and has looked for medications to target them. D’Adamio recently identified clonazepam, a drug that is FDA approved for treatment of anxiety and seizure disorders, capable of targeting these biological pathways. Because clonazepam is safe, it is likely to move through clinical trials more quickly than a new drug. D’Adamio has also discovered two new drug candidates—JCasp and ISVAID. These new potential drugs interact with a protein called amyloid precursor protein, which is known to cause hereditary Alzheimer’s disease, and they are designed to stop the protein-buildup process, observed in the disease, before it begins.
The research by Ahn addresses why people with cardiovascular disease have a higher risk of Alzheimer’s disease. One factor may be blood clots. As blood vessels age, they tend to become rigid or leaky. This can lead to micro-bleeding, which can cause micro-clotting. Ahn has discovered that, in people with Alzheimer’s disease, a protein called fibrinogen interacts with beta-amyloid protein and prevents clot breakdown, allowing clots to build up and block blood flow to small parts of the brain. Ahn is working to identify drugs that block the interaction between fibrinogen and beta-amyloid protein, as well as studying the brain-related effects of other vascular problems, such as inflammation and the buildup of proteins on the outside of blood vessels.
D’Adamio and Ahn have also made breakthroughs in laboratory-testing methods. D’Adamio has used genetic modification approaches to create novel animal models of Alzheimer’s disease that can be used to study the etiology (cause) of the disease and to evaluate novel drugs. Ahn has created a new fiber-optic technique that allows him to study brain function during wakefulness, not just under anesthesia.
These testing breakthroughs are important because preclinical trials (lab tests) are necessary for gaining FDA approval to begin clinical trials (studies using people). Up to this point, Rutgers researchers have been able to engage only in the former. But that is about to change.
“Rutgers’ plan is to look for treatments for all types of Alzheimer’s disease, develop new theories, and test them,” says Klein. “To do that, they need a full Alzheimer’s center with a patient clinic. I’m very proud to be able to help them work toward that.”
Putting an End to a Pernicious Disease
Alumnus Herbert Klein makes another gift to help underwrite dementia research.
Over the past decade, Herbert Klein has dedicated more than $2 million to the support of Alzheimer’s and dementia research at the Brain Health Institute. The funding has enabled Rutgers to recruit Luciano D’Adamio and Hyung Jin Ahn and set up labs to form the nucleus of an Alzheimer’s research program.
To help Rutgers take the next logical step—to human trials—Klein RC’51 committed $5 million more in August. The gift will establish the Herbert and Jacqueline Krieger Klein Alzheimer’s and Dementia Clinical Research and Treatment Center, as well as the Jacqueline Krieger Klein Endowed Director’s Chair in Neurodegeneration Research, a position that will establish the center’s long-term vision and direct daily operations. “We have a special committee looking to recruit a leading clinical trialist with extensive background and experience,” says Brian Strom, chancellor of Rutgers Biomedical and Health Sciences. “We’re looking for a star.”
The ideal candidate will work closely with the scientists conducting lab research. “I’m excited to collaborate with a person in the clinical area who actually works with the Alzheimer’s patient,” says Ahn. “This is a great step in the right direction.”
In a few years, the new center is anticipated to begin clinical trials on drug candidates (like clonazepam) that have been identified in Rutgers’ labs.
Herbert and his son, Roger Klein, are excited to watch this transformation. “I’m so grateful for the scientists at Rutgers,” says Roger. “My mother would be proud of what they are doing for our community, our society—and families just like ours.”