PAMs: Better Treatment for Alzheimer’s?

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Alzheimer’s disease is the sixth leading cause of death in America, and one of the most expensive, costing us 172 billion dollars annually. We know that there is no cure, yet. But is there a way to slow its progression? A new type of substance is being tested for its effectiveness could eventually serve as a treatment for Alzheimer’s and other cognitive diseases. It’s called a PAM.

What are PAMs?

Positive Alosteric Modulators (PAMs) offer a new kind of solution to an old problem: aging brains with weakening inter-cellular communication. PAMs may help strengthen communication at weakening synapses within the brain. And they would do so in a unique way.

BYU PhD neurology student Doris Jackson provides a simple analogy to explain how PAMs function. “The receptor on a neuron is like a door. And a substance called an agonist is like the key that opens the door; while an antagonist locks the door, or blocks the neurotransmitters.” This opening and closing of doors is how cells communicate. If you have a neurologically degenerative disease like Alzheimers, you have unhealthy connections between neurons, meaning the “doors” have moved farther apart, making it more difficult for signals to pass through. “A lot of pharmacological drugs just add more agonists to the system (i.e. more keys that open the door),” says Jackson. “So more doors are opening; even when they’re not normally supposed to open.” PAMs, however, do not act as a key. They don’t open doors, rather, they open them wider, or keep them open longer.

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“When we use PAMs,” says Jackson, “We’re keeping the normal opening and closing of the doors the same. All of that is functioning normally, but we allow a greater response to occur.” So PAMs may allow for a more natural, and potentially more effective treatment for ailments in the brain. 

 

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PAMS and the Bigger Picture of Alzheimer’s Research

PAMs have shown lots of potential for becoming a part of Alzheimer’s treatment medications in the future, although studies are still in the preliminary stages. They are also being used to differentiate between different subtypes of receptors—which may lead to the creation of medications with less severe side effects.

Jackson, along with Marcel Killpack Hall, a lead researcher on a student team studying PAMs at BYU, presented their findings at our recent Mary-Lou Fulton Mentored Research Conference, taking first place in the division of Neuroscience.

“Currently,” says the Alzheimer’s Association, “there are five FDA-approved Alzheimer’s drugs that treat the symptoms of Alzheimer’s—temporarily helping memory and thinking problems in about half of the people who take them. But these medications do not treat the underlying causes of Alzheimer’s. In contrast, many of the new drugs in development aim to modify the disease process itself, by impacting one or more of the many wide-ranging brain changes that Alzheimer’s causes.”

The possible implications of this Jackson and Hall’s mentored research are exciting to consider, especially in light of the increased body and momentum of research into predicting and treating Alzheimer’s disease.

 

Have you or anyone you know been affected by Alzheimer’s? What do you think about this research?

 

 

 

 

Predicting Alzheimer’s Disease

Over 5 million Americans have Alzheimer’s disease. It is highly likely that you or a loved one knows someone who has been affected. And although Alzheimer’s is quite commonplace among aging individuals, it is not just a symptom of normal aging. It is a progressive, fatal disease. It is one that can potentially be cured or prevented with further research. And while the cure has not yet been found, some BYU FHSS faculty have been gathering data that is promising for the future.

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Dr. Jonathan Wisco

Dr. Jonathan Wisco, associate director of the MRI lab here at BYU, has a special interest in studying the effects of Alzheimer’s disease on the brain – particularly the early stages of the brain degeneration. He’s looking for what he calls the “Holy Grail” of Alzheimer’s research: early indicators of Alzheimer’s disease in brain tissue, and he spoke about this research at our recent gerontology conference.

Many outward expressions of brain degeneration are commonly seen at the beginning stages of several different types of dementias. The problem is that it is virtually impossible to tell which way the brain and body will go from there. Will it be to Parkinson’s, Frontotemporal Dementia, or Alzheimer’s?  For the past several years, Wisco has been studying the brain to find what might indicate the track a particular individual is on – and thus aid in the future treatment of that person.

Symptoms of Alzheimer’s disease include:

  • Memory Loss
  • Executive system function deficits
  • Difficulty planning/solving problems
  • Difficulty with familiar tasks
  • Confusion of time and place
  • New problems with speaking or writing
  • Inability to retrace steps
  • Social withdrawal
  • Depression
  • Changes in mood and personality
  • Night terrors

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There are also 2 different types of Alzheimer’s:

  • Familial Alzheimer’s is translated genetically, and it often comes up in the fifth or sixth decade of life, with a quick deterioration of the brain.
  • Sporadic Alzheimer’s is the most common form of the disease, and it typically begins in the eighth decade of life and beyond.

Before coming to BYU, Wisco knew the symptoms of Alzheimers, those that manifested within the brain as well as those that manifested outside it. He collected a lot of data before coming to BYU. But he didn’t know quite what to do with it all.

“At one point while I was at UCLA my work had stalled. I had no idea how I was going to interpret [some data] I had come up with,” said Wisco. “Then when I arrived here at BYU, Dr. Kauwe from Biology invited a bunch of us faculty  who were interested in Alzheimer’s to meet together. Dr. Richard Watt from the Chemistry  department was in attendance, he had some data that he couldn’t make sense of, and his data was all over the map, as was mine.” Wisco and Watt did some comparisons and were able to make some links between symptoms that could potentially be predictors of Alzheimer’s disease.

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Wisco and Watt have worked together for some time now, and have been able to find some potentially groundbreaking evidence of predictors for Alzheimer’s. “What we didn’t expect to find in our research was that the inflammatory  response is probably contributing to signal decay. The pathological response to the disease itself is causing more problems in individuals with Alzheimer’s.”

“The results were exciting to see,” said Wisco. “And we’re curious and anxious to know if this is happening in different parts of the brain that we haven’t yet analyzed.”

Wisco’s research is expected to continue, and they are awaiting  further results from their lab research. And so far, “The results look  promising.”

Do you know someone with Alzheimer’s?