Alzheimer’s: UNM researchers may be closing in on a cure

A healthy neuron field, left, and a neuron field with Alzheimer’s cells. The tau tangles are inside the neurons and the beta-amyloid plaques are outside the neurons. (Courtesy of Alzheimer’s Association/illustration by Stacy Janis)

A healthy neuron field, left, and a neuron field with Alzheimer’s cells. The tau tangles are inside the neurons and the beta-amyloid plaques are outside the neurons. (Courtesy of Alzheimer’s Association/illustration by Stacy Janis)

Copyright © 2015 Albuquerque Journal

Researchers at the University of New Mexico Health Sciences Center say they are getting closer to a vaccine that could someday rescue people from Alzheimer’s.

Although still years away, the hope is it could treat or even prevent the disease, and at a lower cost than other potential cures being researched.

Dr. Kiran Bhaskar, assistant professor of molecular genetics and microbiology, department of neurology, University of New Mexico Health Sciences Center, and his team are working on a vaccine that could treat and prevent Alzheimer’s disease. (Courtesy of UNM Health Sciences Center)

Dr. Kiran Bhaskar, assistant professor of molecular genetics and microbiology, department of neurology, University of New Mexico Health Sciences Center, and his team are working on a vaccine that could treat and prevent Alzheimer’s disease. (Courtesy of UNM Health Sciences Center)

Assistant professor Kiran Bhaskar and his team have developed a vaccine that restores cognition in mice engineered to develop Alzheimer’s disease. It also reverses changes in their brains that indicate the presence of the disease.

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The researchers say the vaccine could be in human trials in less than five years, but they hope even sooner.

The results of their research are scheduled to be published by the end of the year. Bhaskar has targeted the journal Nature Medicine.

“We are looking at a biomarker for the diagnosis of Alzheimer’s disease. We are trying to induce an immune response against the changes of Alzheimer’s disease that is strong and long lasting, but avoids side effects,” Bhaskar says. “As of our human research pilot award, we are still waiting to know the funding decision. Looks like it is getting pushed until October.”

The initial pilot grant from Clinical Translational Science Centers, funded through the National Institutes of Health, would support a study to examine the blood of people with Alzheimer’s and those without it to measure and compare the presence of the biomarker, an abnormal tau protein.

The project will require Food and Drug Administration (FDA) approval before the vaccine could be studied in humans, he says.

The advantage to this research over other similar efforts is that the UNM team is working with a vaccine that is less costly.

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“If it is cheaper, then it is affordable to millions,” Bhaskar says.

The heat is on, because Alzheimer’s disease affects 5.3 million people nationwide and is the sixth leading cause of death.

Alzheimer’s and other dementias are expected to cost $226 billion this year, according to the Alzheimer’s Association. It projects the number of people with the disease will triple to 15 million and more by 2050 without a treatment or cure.

Dr. Kiran Bhaskar, left, works with lab manager Nicole Maphis in their lab at the University of New Mexico Health Sciences Center. Dr. Bhaskar and his team are working on a vaccine that could treat and prevent Alzheimer’s disease. (Courtesy of UNM Health Sciences Center)

Dr. Kiran Bhaskar, left, works with lab manager Nicole Maphis in their lab at the University of New Mexico Health Sciences Center. Dr. Bhaskar and his team are working on a vaccine that could treat and prevent Alzheimer’s disease. (Courtesy of UNM Health Sciences Center)

A new path

One recent morning in a lab on UNM’s north campus, Bhaskar described his team’s vaccine and their work with tau, a protein in neurons that becomes tangled and toxic in people with Alzheimer’s. It results in progressive, debilitating loss, beginning with activities of everyday life and ending with death.

Toxic tau is one of two proteins that accumulate in brains of those with Alzheimer’s. The other, beta-amyloid, causes an accumulation called plaques.

“For 30 years, we’ve been going down the amyloid path. They have developed pharmaceuticals for beta-amyloid. They saw beautiful clearance of the plaques in the brain, but there is no clinical correlation (for cognitive decline),” Bhaskar says, explaining that, although the plaques were cleared, the dementia remained.

In a Mayo Clinic study reported in the March journal of Brain, scientists looked at the brains of more than 3,600 people, some with Alzheimer’s and some not, and learned that tau, not beta-amyloid, is the major driver behind the cognitive decline.

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Tau tangles derail the brain’s neuron highway, says Bhaskar’s research associate Nicole Maphis. Like a bridge collapsing, brain traffic has no way to move. While the toxic tau is correlated with Alzheimer’s, it is also present in people with traumatic head injuries, Parkinson’s and other neurologic disorders.

As the tangles and amyloid plaques accumulate, the microglia, the brain’s immune cells, in an effort to respond, misfire and become overactive, creating a very toxic inflammatory response, she says.

a01_jd_09aug_ALZHEIMER-S-CASESBrain is dying

The dying brain shrinks, and changes in function and behavior become more evident, says Dr. Janice E. Knoefel, a neurologist and gerontologist at UNM Health Sciences Center. “First, we see impairment with financial management and driving. Then, shopping, cooking and cleaning, and eventually personal hygiene,” she says, adding that eventually all functions, even talking and swallowing, are affected.

Bhaskar and his team have targeted a particular kind of pathological tau, called phosphorylated tau, to create their vaccine. The vaccine is created with virus-like-particles, a strategy for vaccine creation developed at the UNM Health Sciences Center by Drs. David Peabody and Bryce Chackerian.

The immune system responds to the virus-like-particles loaded with molecules of the targeted pathology, in this case the phosphorylated tau, Bhaskar says. The immune response develops against the target and specifically destroys the brain’s own pathologically modified forms of tau.

In memory and cognition tests, the Alzheimer mice treated with the new vaccine performed similarly to wild-type mice that are not engineered to develop Alzheimer’s. The vaccine-treated Alzheimer mice performed much better than Alzheimer mice with a different vaccine, Maphis says. On autopsy, their brains revealed significantly fewer tangles and reduced inflammation than the Alzheimer mice that were not specifically vaccinated for tau.

a01_jd_09aug_ALZHEIMER-S-GENDER-1New collaboration

While human application of such a vaccine may still be years away, the cooperation between researchers and clinicians helps speed innovation from the lab bench to the bedside, perhaps creating a future when Alzheimer’s will become a disease of the past, mostly controlled, like polio.

The collaboration of a clinical doctor like Knoefel and a research scientist like Bhaskar has been rare in the past, they say. “This is really helpful,” Knoefel says. “We want there to be a realistic translation from research to clinical application.”

Other UNM colleagues are researching Alzheimer’s disease.

Dr. Elaine Bearer, a pathology professor, also has an ongoing research program. Her work suggests the extent of damage to a brain’s circuitry and neuron highway in a mouse model. Another investigator, Dr. Laurel Sillerud, professor and director of MRI Core, is developing nanoparticle technology to label plaques, tangles and inflammatory changes in the brain, which would some day serve as a biomarker to conclusively diagnose Alzheimer’s disease.

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