More than six million Americans are currently living with Alzheimer’s disease (AD). While there is no cure for this devastating illness, several pharmaceutical companies are working to develop immunotherapeutic vaccines designed to prevent and reduce AD symptoms. Now, through a series of experiments with Alzheimer’s mouse models, University of Kansas researchers have discovered a possible new approach to AD immunization. The findings, which were recently published in Antioxidants, have the potential to reduce the impact of AD on a rapidly aging population.
Creating Vaccines to Fight Alzheimer’s
Immunotherapeutic vaccines activate the body’s immune system to help fend off a certain type of cell. In the case of the University of Kansas study, researchers were hoping to “teach” the immune system to produce antibodies against methionine sulfoxide, or MetO. MetO is a component of amyloid-beta, or Abeta, the toxic protein that is seen as the most common hallmark of Alzheimer’s disease. The team created a vaccine using a MetO-rich protein to “introduce” the body to MetO, allowing the body to produce antibodies against MetO-harboring Abeta. The goal was to eventually reduce the toxic levels of Abeta in the brain, improving memory outcomes and preventing the key symptoms of AD. To test the method, the researchers worked with Alzheimer’s mouse models.
Testing the Alzheimer’s Mouse Models
The University of Kansas team injected the MetO-rich protein into four-month-old mice that had been genetically modified to develop the familial form of AD. The team was successful; the models’ immune systems were found to produce the necessary antibodies to fight off MetO-harboring Abeta. But the team still had to determine if the antibodies were enough to reduce AD symptoms in mice that were genetically engineered to develop AD.
To find out, the researchers assessed the memory of injected mice against a group of control mice. One such test was a Y-maze test, which involved placing a mouse in a maze shaped like a “Y.” During this test, the mice were allowed to explore the left and right arms of the maze; after that, researchers introduced a third arm in the middle to see if the mice recognized the third arm as a new space worth exploring. The researchers also used the Morris water maze test. During this test, mice are placed in a circular pool of opaque water and must swim to an escape platform. Because they cannot see the platform, they must use external cues to figure out the escape route, demonstrating spatial memory and learning.
After a number of similar tests, the researchers evaluated the models’ Iba1 expression to determine if the vaccine had any other neurological outcomes. Ultimately, the researchers found that the vaccine led to a roughly 50 percent improvement in the memory of injected mice. The injected mice also showed signs of improved long memory capabilities, reduced Abeta levels, and elevated antioxidant capabilities.
Could Alzheimer’s Vaccines Be on the Way?
The University of Kansas researchers found that active immunization “could give a possibility of delaying or preventing AD onset.” With that in mind, researchers could administer a similar treatment to older individuals at risk of Alzheimer’s disease, following the initial vaccination with a booster shot regimen to stave off AD symptoms as individuals age. However, such a treatment may be in development for years, as researchers still need to begin clinical studies in human subjects.
While the researchers still need to conduct clinical trials in humans, studies like this one prove that neuropharmacological innovation is the medical community’s best hope at fighting debilitating diseases like Alzheimer’s.
QPS Neuropharmacology is a division of QPS, a GLP/GCP-compliant contract research organization (CRO) delivering the highest grade of discovery, preclinical, and clinical drug development services since 1995. QPS Neuropharmacology focuses on preclinical studies related to central nervous system (CNS) diseases, rare diseases, and mental disorders. With highly predictive disease models available on site and unparalleled preclinical experience, QPS Neuropharmacology can handle most CNS drug development needs for biopharmaceutical companies of all sizes. To study Alzheimer’s disease, QPS Neuropharmacology offers several in vitro models, animal models as well as behavioral tests and ex vivo analysis methods. For more information about QPS visit www.qps.com, and for more information about QPS Neuropharmacology, visit www.qpsneuro.com.