For Frank Stephens, 40, the effort to defeat Alzheimer’s is personal.
One reason is that the disease left her mother “almost childish,” she says. “It’s very hard to see.”
Also, as a person with Down syndrome, Stephens knows that he is more likely to have Alzheimer’s than his mother.
So she raised money for Alzheimer’s research through the Global Down Syndrome Foundation and she took part in research studies through the group’s Human Trisome project.
Stephens’ goal is to find a drug that can prevent Alzheimer’s.
“It would be amazing,” he says. “I hope I can do it for my mom.”
The extra chromosomes, the extra risk
People with Down syndrome are very much looking for Alzheimer’s research because many of them develop the disease in their 40s and 50s and most will get it if they live longer.
Excess duplication of chromosome 21 carried by people with Down syndrome leads to a higher risk of Alzheimer’s.
This extra genetic code leads to intellectual disability. Joaquin Espinosa, executive director of the Linda Chronic Institute for Down Syndrome and professor at the University of Colorado’s Anshutz Medical Campus, says it alters the brain in at least two ways that can lead to Alzheimer’s.
As a result, he said, “People with Down syndrome have a unique opportunity to understand what changes the severity and progression of Alzheimer’s disease.”
A hyperactive immune system
Down syndrome is associated with a hyperactive immune system. It protects patients from some cancers, but also leads to chronic inflammation.
“And important for Alzheimer’s,” says Espinosa, “they have encephalitis throughout their lives.”
There is growing evidence that encephalitis plays an important role in Alzheimer’s. So Espinosa and a team of researchers are looking for ways to control the immune system of the brain.
“We are conducting clinical trials for immune modulating agents in Down syndrome,” he says. “An active trial is currently underway to reduce 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 that these drugs can reduce inflammation in the brain and reduce the risk of Alzheimer’s, and he is trying this approach in people with Down syndrome.
Excess chromosomes, extra amyloid
Another team from the Chronic Institute is taking a different approach to modifying the immune system.
Dr. Huntington Potter says the idea is to increase immunity to a particular disease that “eats things that aren’t supposed to be there.”
One of these things is amyloid, a sticky, toxic substance that builds up in the brains of people with Alzheimer’s. People with Down syndrome have more amyloid in their brains because their extra chromosomes contain genetic instructions for making substances.
Potter hopes to prevent it with a drug called leucine, which increases the number of immune cells that eat amyloid.
Last year, he conducted a small study showing that leucine could be safely given to people with Alzheimer’s.
“We didn’t expect to see a cognitive advantage,” he says. “But three weeks of treatment with leucine and individuals have improved their knowledge.”
These people did not have Down syndrome. But in March, Potter’s team showed that leukine also worked in rats with Down syndrome.
“We then allow adults with Down syndrome to apply for grants for the study before they develop Alzheimer’s disease,” he says.
They received a 4.6 million grant from the National Institute on Aging. Now they need to recruit young adults who have Down syndrome to study.
That shouldn’t be a problem, says Lina Patel, director of neurodevelopmental, cognitive and behavioral assessment at the Chronic Institute.
“The self-advocates we work with are really advocates of research,” he says. “They see that it is directly affecting their lives and the lives of others.”