Local experts work to unlock cure to Alzeheimer’s disease

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Research is the key to ending Alzheimer’s disease, and the McLaughlin Research Institute in Great Falls is doing some of the leading research in the world on the disease.

From testing on mice models to administering clinical trials on Alzheimer’s patients, Great Falls is progressive in its attack on the disease.

“The McLaughlin Research Institute is working on the basic science of it in mice, and I’m working on clinical trials in people,” said Great Falls neurologist Dennis Dietrich, who is the only doctor in the state currently enrolling patients in Alzheimer’s clinical trials. “I’m on one end and McLaughlin is on the other. Both are critical to advance medical science and develop new treatments.”

One of the most exciting revelations researchers have uncovered is the link between various diseases.

“Everything is coming together,” said McLaughlin Director George Carlson. “They are all caused by misfolded proteins.”

McLaughlin has evolved into a degenerative brain disease institute, Carlson said. And not only could the research specific to Alzheimer’s disease be the key to unlocking its mystery, so could the research from a whole class of deadly brain diseases the institute is studying, including prion diseases, Parkinson’s and Huntington’s disease.

These diseases start in one area of the brain and spread to the rest. Now that scientists know these misfolded proteins spend part of their time outside of cells — traveling from one cell to another — new drugs can target them there. This could help prevent or at least block the progression of these diseases.

“Aggregated protein causes the normal protein to misfold and spread from cell to cell,” Carlson said.

Research breakthroughs on any of these diseases could offer the missing puzzle piece to Alzheimer’s, or at least lead scientists toward a treatment that could delay the onset of Alzheimer’s.

While scientists and doctors ultimately want to find a cure for this disease that affects 5.4 million people in the United States, delaying the onset of Alzheimer’s would be a huge step in the right direction.

Delaying the onset of this disease, which is the sixth-leading cause of death in the United States, could drop the numbers of those ever affected as many people may reach the end of their lives before symptoms emerge.

Nearly half — 43 percent — of Americans older than age 85 suffer from Alzheimer’s, which is the most common form of dementia.

Delaying the disease also could greatly reduce health care costs.

“The research that leads to a treatment that would delay Alzheimer’s by five years would cut government spending for Alzheimer’s disease by 45 percent by 2050,” said Suzanne Belser, executive officer of Alzheimer’s Association Montana.

“The costs of caring for AD patients is immense — currently $200 billion in 2012, and projected to increase to $1.1 trillion by 2050 if no therapy is found, putting a tremendous strain on health care providers and insurers — including Medicare,” Carlson added.

Looking at the growing number of dementia patients in Montana’s nursing homes and assisted-living facilities is worrisome, Dietrich said. Few people are wealthy and able to pay privately, some are poor and their care is paid through Medicare and Medicaid programs, while others pay with long-term care insurance.

“You’ll spend $60,000 to $80,000 a year (for a care facility). There are very few people who can afford it,” he said.

And with fewer people paying into those programs as the large numbers of baby boomers hit retirement age, “something has to give,” he said.

A lack of funding is slowing research.

Belser said the United States spends far less on Alzheimer’s research than other diseases.

About $6 billion was spent on cancer research, $4 billion on heart disease research and $3 billion on AIDS research in 2011, Belser said. Approximately $480 million was spent on Alzheimer’s research.

Change may be coming, however.

The Alzheimer’s Association, which is the leading global voluntary health organization in Alzheimer’s care and support, and the largest private, nonprofit funder of Alzheimer’s research, spearheaded a national push that is leading to more funding.

The Obama administration recently released a draft national plan to address Alzheimer’s disease, which included $130 million in new funding for Alzheimer’s research over the next two years.

Belser will go to Washington, D.C., this week to lobby for several U.S. House and Senate bills aimed at increasing the commitment to and funding for Alzheimer’s research, and expanding diagnosis of the disease.

Currently, the diagnosis of Alzheimer’s relies largely on recognizing memory loss. Typically, a loved one notices the patient has been making out-of-the-ordinary decisions. By the time the patient sees a doctor and is diagnosed, there already has been significant brain damage.

“If we have a treatment to slow down the disease, when would you want to start it?” Dietrich asked. “Before the signs are obvious.”

Researchers hope a biomarker can be found that would serve as an early indicator of the disease, much like high cholesterol can indicate increased risk for coronary heart disease. They are working to “validate” a biomarker, which means it needs to be confirmed by multiple studies in large groups of people.

Current research is working toward identifying biomarkers using several tools, including brain imaging, levels of proteins in cerebrospinal fluid, levels of proteins in blood and genetic risk profiling.

There isn’t a treatment available to slow or stop the deterioration of brain cells in Alzheimer’s disease, but the U.S. Food and Drug Administration has approved five drugs that lessen symptoms and improve daily functioning for six to 12 months, but do not prevent the disease progression.

There also are about 100 experimental therapies in clinical testing in human volunteers across the world, according to the Alzheimer’s Association.

Carlson said once family members complain about dementia in their loved ones, it is less likely that newly developed therapies will be successful. Brain changes in those with Alzheimer’s are thought to begin 10 years or more before the appearance of symptoms such as memory loss, according to the Alzheimer’s Association.

Another research obstacle is a lack of trial participants.

“It’s easy to get approval for Alzheimer’s patients, but it’s too late,” Carlson said.

However, people who have a family history of three rare familial forms of Alzheimer’s have helped researchers.

In these trials, the drugs can be given to patients who know they carry the tainted gene but haven’t yet displayed symptoms.

A Colombian family of more than 5,000 people is among those involved in research.

The hope is that researchers will find a drug that will work on familial forms of the disease and it also will work on the sporadic, more common form of the disease, Carlson added.

He said the McLaughlin Research Institute made its first mouse model to research Alzheimer’s in 1988. These transgenic mice express a faulty human gene, called APP, which is a cause of familial early onset Alzheimer’s. There are several mouse models in labs across the world, all mimicking Alzheimer’s, but the disease behaves differently in mice and humans, Carlson said.

Human brains with Alzheimer’s first develop beta-amyloid plaques, followed by tangles that lead to the death of brain cells. The APP mice don’t develop tangles.

“These Alzheimer’s mice only have plaques,” Carlson said. “We’d really like to reproduce the whole (spectrum of) Alzheimer’s disease.”

Scientists used to think tangles came before the beta-amyloid plaques, but it has been discovered that the plaques occur first. Mice expressing a different mutant gene have been developed that accurately model the tangles seen in Alzheimer’s disease and frontotemporal dementia.

This is important to researchers working on a biomarker, with advances being made in the ability to detect the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain.

“What we think is that the mice with plaques are models for pre-clinical Alzheimer’s, while the mice with tangles are more relevant to later-stage disease,” Carlson said.

Dietrich has administered clinical trials on promising Alzheimer’s drugs for 20 years. The drug he currently has in clinical trials, Bapineuzumab, is being tested by Janssen Pharmaceuticals and Pfizer, Inc.

The school of thought is to passively vaccinate against beta-amyloid plaques in the brain.

“If you develop an antibody, then you can attack the target with it,” Dietrich said. “Bapineuzumab attaches to beta-amyloid and helps remove it from the brain.”

The drug, which is administered through an IV, already has been shown to reduce the plaques in the brain, Dietrich said.

Scans have shown the drug’s success in reducing beta-amyloid plaques in the brain, but researchers still are unclear as to whether it slows the progression of the disease.

“We hope to have some results from our first study by the end of this year,” he said.

Dietrich is enrolling patients in a second trial for Bapineuzumab, this one through Pfizer. The trial is scheduled for completion in 2014.

To be eligible for the trial, patients need to be experiencing only mild to moderate symptoms of Alzheimer’s, and be between the ages of 50 and 88, with no other major health issues, he said. Great Falls is one of 292 trial sites.

“I’m not seeing hundreds of people in this trial. It’s a very small trial,” Dietrich said.

To measure whether the drug works, patients will undergo extensive cognitive testing and need to sit still through a 45-minute MRI.

“If the brain shrinks, it may indicate that you’ve lost brain cells,” Dietrich said.

The ratio of phosphorylated tau and the decreased a-beta in spinal fluid also is measured as a means of determining if the drug is working.

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Source: greatfallstribune.com

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