For Frank Stephens, 40, the effort to defeat Alzheimer’s is personal.
One reason is that the disease has left his mother "almost childlike," he says. "It is very hard to see."
Also, as a person with Down syndrome, Stephens knows that he is likely to develop Alzheimer's much earlier than his mother did.
So he raises money for Alzheimer's research through the Global Down Syndrome Foundation and he takes part in research studies through the group's Human Trisome Project.
Stephens' goal is to help find a drug that stops Alzheimer's.
"That would be amazing," he says. "I'm hoping I can do that for my mother."
Extra chromosome, extra risk
People with Down syndrome are highly sought after for Alzheimer's research studies because many develop the disease in their 40s and 50s, and most will get it if they live long enough.
The elevated risk for Alzheimer's comes from the extra copy of chromosome 21 carried by people with Down syndrome.
This extra genetic code leads to intellectual disability. It also changes the brain in at least two ways that can lead to Alzheimer's, says Joaquin Espinosa, executive director of the Linda Crnic Institute for Down Syndrome and a professor at the University of Colorado's Anschutz Medical Campus.
As a result, he says, "People with Down Syndrome give us a unique opportunity to understand what modulates the severity and the progress of Alzheimer's disease."
A hyperactive immune system
Down syndrome is associated with a hyperactive immune system. That protects people with the condition from some cancers, but also leads to chronic inflammation.
"And of importance to Alzheimer's," Espinosa says, "they have brain inflammation across the lifespan."
There is growing evidence that brain inflammation plays an important role in Alzheimer's. So Espinosa and a team of researchers are looking for ways to keep the brain's immune system in check.
"We are running clinical trials for immune modulating agents in Down syndrome," he says. "There is an active trial right now to tone down that response with a class of drugs known as JAK inhibitors."
JAK (Janus kinase) inhibitors are used to reduce inflammation in people with rheumatoid arthritis and other autoimmune diseases.
Espinosa hopes these drugs can also reduce inflammation in the brain and cut the risk of Alzheimer's and he is trying the approach in people with Down syndrome.
Extra chromosome, extra amyloid
Another team at the Crnic Institute is taking a different approach to modulating the immune system.
Dr. Huntington Potter says the idea is to boost a special immune cell that "eat(s) up things that aren't supposed to be there."
One of those things is amyloid, the sticky, toxic substance that builds up in the brains of people with Alzheimer's. People with Down syndrome tend to have more amyloid in their brains because their extra chromosome includes genetic instructions to make the substance.
Potter hopes to prevent this with a drug called Leukine, which increases the number of immune cells that eat amyloid.
Last year, he did a small study to establish that Leukine could safely be given to people with Alzheimer's.
"We did not expect to see a cognitive benefit," he says. "But three weeks of treatment with Leukine and the individuals actually improved in their cognition."
Those people did not have Down syndrome. But in March, Potter's team showed that Leukine also worked in mice that did have Down syndrome.
"That then allowed us to apply for a grant to study young adults with Down syndrome before they get Alzheimer's disease," he says.
They got the $4.6 million grant from the National Institute on Aging. Now they need to recruit young adults who have Down syndrome for the study.
That shouldn't be a problem, says Lina Patel, director of neurodevelopmental, cognitive and behavioral assessment at the Crnic Institute.
"The self-advocates that we work with really are proponents" of research, she says. "They see that it is directly impacting their lives and the lives of others."
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