LSU researchers are seeking to end Alzheimer’s disease and start a new neurobiotech industry in Louisiana
(Jeffrey Keller, founder and director of the Institute of Dementia Research & Prevention, is among a number of LSU researchers looking to prevent and find a cure for Alzheimer’s disease. Photography by Collin Richie)
Off the shores of Waikiki in Hawaii, the invasive species Bugula neritina—a colonial animal that grows in bushy tufts and is often mistaken for seaweed—has taken hold, just as it has along the Pacific Coast, Eastern seaboard and Gulf Coast.
Despite the environmental havoc the pest species brings, the pervasiveness of this sea moss could provide a breakthrough in the treatment of one of the most devastating and costly diseases of modern times, says J. Steven Alexander, a professor in the Department of Molecular and Cellular Physiology at the LSU Health Sciences Center in Shreveport.
Alexander and his colleagues have discovered that a byproduct of Bugula neritina may hold a key to developing a treatment for Alzheimer’s disease, the most prevalent form of dementia. It’s a devastating affliction that affects memory and cognition, and “robs people of their identity and their personality,” as Alexander puts it.
Working with Boston-based Aphios Corp., Alexander’s research has found that an oral form of the drug, Bryostatin-1, originally designed to treat cancer, seems to reverse Alzheimer’s in mice. Although Bryostatin-1 was not an effective cancer drug, it has a positive effect on cognition. The drug acts on neurons as well as blood vessels.
“It stabilizes the vascular system against the inappropriate penetration of the brain by inflammatory immune cells,” explains Alexander, who adds that disturbances of the neurovascular system contribute to brain diseases beyond Alzheimer’s, including multiple sclerosis, Parkinson’s disease and dementia.
“There are a lot of related conditions that experience a disturbance of blood vessels in the brain,” Alexander says. “There are two important things going on. One is the mechanism through which the amyloid formed is blocked, and second, the blood-brain barrier that prevents inflammatory immune cell penetration into the brain is destabilized, and that’s a big problem.”
Although Bryostatin-1 could likely be translated to clinical trials quickly, he says the cost remains prohibitive, as divers must collect the sea moss and large quantities are needed. Developing an affordable form of the drug is paramount, he adds. Yet Alexander is optimistic about the drug’s future.
“It’s a terrible invasive species, but maybe it can be put to good use,” he says. “We are trying to clean up the environment and simultaneously develop source material for Alzheimer’s.”
EYEING THE CAUSE
Alexander is one of several LSU scientists working on finding a cure for Alzheimer’s disease. At the LSU Health Sciences Center in New Orleans, Nicolas Bazan, director of the Neuroscience Center for Excellence, studies fundamental cellular and molecular lipid signaling taking place in early stages of neurodegenerations and other brain and retinal dysfunctions.
Bazan and his colleagues have discovered neuroprotectin D1, or NPD1, a protective mediator made in the brain after injury or at the onset of seizures or neurodegenerations, including Alzheimer’s disease. In addition to the brain, NPD1, which derives from an essential omega-3 fatty acid, also is made in the eye, so Bazan’s research focuses on the brain as well as the retina.
Using samples from donors both with and without the disease, Bazan examined the areas of the brain that are involved in cognition and memory. He found there was a dramatic shortage of NPD1 in the brain memory areas of donors who were in the early stages of Alzheimer’s.
“There is a relationship of disease in the retina to Alzheimer’s disease, and we are trying to understand this,” Bazan says. “Neuroprotectin D1 comes from a component of our brain and eyes that derives from diet. We need the precursor of NPD1 in our diet.”
After we digest omega-3 fatty acid, Bazan says, it ends up in our brain and retinas more than any other part of the body and is stored in cell membranes.
“When a defense mechanism is needed, it releases part of it and makes more of the protective mediator—it’s made on demand,” Bazan says. “We just discovered the necessary protein for the retention of these fatty acids in cells, and we began uncovering the molecular principles of how it elicits its protective functions. These have given rise to intellectual properties that will be developed to move the basic science into clinical applications.”
Yet simply adding more omega-3 to our diet is not the answer. “As we age, the amount of omega-3 fatty acid we have goes down, even if we keep eating it,” Bazan says, adding scientists are just beginning to understand why the brain and retina are rich in omega-3 fatty acid.
“But we don’t understand what happens when we inject or eat omega-3 and what happens from there to the brain or eye,” he says. “My lab discovered that it has to go through the liver before getting to the brain or retina, so the liver is a key portal gate.”
In clinical trials where omega-3 is given to patients with Alzheimer’s, the results are not clear. “The reason is we don’t understand the significance of the gastrointestinal tract microbiome and the route of our liver to blood circulation,” Bazan says. “We are trying to understand the black boxes between the liver and the brain.”
PUSHING FOR PREVENTION
At LSU’s Pennington Biomedical Research Center, Jeffrey Keller focuses on research that will prevent Alzheimer’s disease from developing in the first place. As founder and director of the Institute of Dementia Research & Prevention, Keller oversees multiple clinical trials and studies designed to identify the risk factors for Alzheimer’s and dementia, more effectively detect and monitor early stages of the disease and, ultimately, develop therapeutic interventions that will prevent Alzheimer’s from developing.
“Prevention is different than treatment,” Keller says. “Not to discount effective treatment, but it is essential that we have ways to prevent, not just treat, Alzheimer’s. Even if we can treat it, the number of people who will develop the disease will still be devastating unless we can find ways to prevent the disease from occurring.”
In 2014, the IDRP was recognized by the Alzheimer’s Disease Cooperative Study as an Alzheimer’s Disease Coordinating Site by the National Institutes of Health. People come from hundreds of miles away to participate in the institute’s trials and studies. IDRP’s trials, which include participation of more than 1,600 Louisianans in the Louisiana Aging Brain Study, have contributed to the evolving understanding of Alzheimer’s.
For example, Keller says, it is now recognized that Alzheimer’s is not one uniform disease, but rather many different types of disease that vary based on pathologies in the brain and other existing diseases and conditions, such as diabetes or hypertension, that a person may have. Keller compares this evolving understanding to how our understanding of cancer has evolved.
“In the 1950s and ’60s, cancer research was based on the thought that all cancer was the same and had the same cause, whether it was breast cancer or pancreatic cancer,” he says. “We look back now and see that was such a simplified concept. That’s where we are now with Alzheimer’s.”
Keller says IDRP is making progress toward preventing Alzheimer’s, in part, because of partnerships with the medical community and other partners. “Our medical community has been really responsive,” he says. “Our work at IDRP is a very complementary approach to the primary care physician.”
Preventing and developing treatments for Alzheimer’s disease has never been more urgent.
“In the next 24 years, we’re going to see triple the number of people with Alzheimer’s disease,” Keller says. “At the same time, the number of caregivers will be reduced by 40 percent because the population is aging. The impact this is going to have on families, businesses and government support is a tsunami headed our way.”
CHALLENGE AND OPPORTUNITY
An estimated 5.1 million Americans may have Alzheimer’s, according to the U.S. National Institute on Aging. That number is expected to increase dramatically to 13.8 million by 2050, according to the Alzheimer’s Association. In Louisiana, the number of people age 65 and older with Alzheimer’s is predicted to rise 34% between 2015 and 2025. An estimated 110,000 Louisianans will be diagnosed with the disease in 2025, the organization predicts.
Although the disease is the sixth leading cause of death in the United States, according to the Center for Disease Control and Prevention, it is the only cause of death in the top 10 that cannot be prevented, slowed or cured. Between 2000 and 2013, deaths from Alzheimer’s disease rose 71%.
“I call it the challenge of civilization,” Bazan says. “This is going to wreck the health care system.”
As more people are diagnosed with the disease, the economic impact of caring for patients will skyrocket. In 2015, Alzheimer’s and other dementias cost the U.S. $226 billion. That figure is predicted to increase to $1.1 trillion by 2050, according to the Alzheimer’s Association. In Louisiana, the economic value of unpaid care for Alzheimer’s and dementia was almost $3.2 billion in 2013, according to the association. Almost 4% of all nursing home beds were designated for Alzheimer’s care in the state in 2014. As the population ages, the demand for memory care facilities will rise, too.
“The cost to society for keeping people with Alzheimer’s comfortable is unimaginable,” Alexander says. “As we live longer lives, we’re sitting on a ticking time bomb of Alzheimer’s cases that will appear.”
Advancements toward preventing or treating Alzheimer’s could revolutionize patient health. At the same time, this could have a tremendous impact on state and regional economic development. The innovative research that scientists such as Alexander, Bazan and Keller are doing could attract new firms and high-skilled workers. Several patents—a sign of innovation—already have resulted from research taking place in Louisiana.
Bazan says applying patents and fostering entrepreneurship to create new companies could lead to what he calls “neurobiotech of Louisiana.”
“Developing startups and attracting branches of big pharma would bring economic development to the region. We need to enhance the presence of academic research in the private sector as translational avenues of knowledge,” he says.
Bazan—whose novel, Una Vida: A Fable of Music and the Mind, about a New Orleans street performer with Alzheimer’s was adapted into a movie this year—envisions South Louisiana becoming a destination for research and treatment related to brain diseases, similar to how MD Anderson in Houston is for cancer research and treatment.
“We can’t become No. 1 in every area of medicine in our region, but we can make neurodegenerative and brain diseases a priority,” he says. “This would attract top companies to the region and, with clinical trials, we could attract doctors and researchers and patients from all over the world. Developing a new domain of knowledge and all the traffic that would generate could have an economic impact on the region and the state, as well as having a huge impact on the well-being of our people.”