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.
“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.
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?