For Frank Stevens, 40, the effort to beat Alzheimer’s is personal.
One reason is that the disease left his mother “almost childlike,” he says. “It’s very hard to see.”
Also, as a person with Down syndrome, Stevens knows that he is likely to develop Alzheimer’s much earlier than his mother.
So he raises money for Alzheimer’s research through the Global Down Syndrome Foundation and participates in research studies through the group’s Human Trisome Project.
Stevens’ goal is to help find a drug that stops Alzheimer’s disease.
“That would be amazing,” he says. “I hope I can do this for my mom.”
Extra chromosome, extra risk
People with Down syndrome are in high demand for Alzheimer’s research because many develop the disease in their 40s and 50s, and most will get it if they live long enough.
The increased risk of Alzheimer’s disease 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 disease, says Joaquin Espinosa, executive director of the Linda Krnick Institute for Down Syndrome and a professor at the University of Colorado Anschutz Medical Campus.
As a result, he says, “People with Down syndrome give us a unique opportunity to understand what modulates the severity and progression of Alzheimer’s disease.”
An overactive immune system
Down syndrome is associated with an overactive immune system. This protects people with the condition from some cancers, but also leads to chronic inflammation.
“And importantly for Alzheimer’s,” says Espinosa, “they have lifelong brain inflammation.”
There is growing evidence that brain inflammation plays an important role in Alzheimer’s disease. So Espinosa and a team of researchers are looking for ways to keep the brain’s immune system in check.
“We are conducting clinical trials for immunomodulatory agents in Down syndrome,” he says. “There is currently an active trial to moderate this 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 reduce 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 “eats things that shouldn’t 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 the genetic instructions for making 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 find that leucine could be safely given to people with Alzheimer’s.
“We didn’t expect to see a cognitive benefit,” he says. “But three weeks of leucine treatment and the subjects actually improved in their cognition.”
These people did not have Down syndrome. But in March, Potter’s team showed that leucine also worked in mice that did have Down syndrome.
“This then allowed us to apply for a grant to study young adults with Down syndrome before they get Alzheimer’s,” he says.
They received a $4.6 million grant from the National Institute on Aging. Now they need to recruit young people with 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 advocates we work with are really supportive” of the research, she says. “They see that it directly affects their lives and the lives of others.”