Frank Stephens, aged 40, finds the fight against Alzheimer’s personal.
He believes that his mother has become “almost childlike” due to the disease. It is difficult to see.
Stephens also knows that his mother, a Down syndrome person, is more likely to get Alzheimer’s than him.
He raises money through the Global Down Syndrome Foundation for Alzheimer’s Research and participates in research projects through the Human Trisome Project.
Stephens has a goal to find a drug that will stop Alzheimer’s.
He says, “That would be incredible.” “I hope I can do that to my mother,” he says.
Extra chromosome, extra risk
Because many people with Down syndrome develop Alzheimer’s disease in their 40s or 50s, most will die.
People with Down syndrome are at an increased risk of developing Alzheimer’s disease because they have an extra copy 21 of chromosome 21.
Intellectual disability is caused by this extra genetic code. It can also alter the brain in at most two ways that could lead to Alzheimer’s. Joaquin Espinosa is the executive director of Linda Crnic Institute for Down Syndrome, and a professor at University of Colorado’s Anschutz Medical Campus.
He says that people with Down Syndrome have a unique opportunity for us to learn what influences the severity and progression of Alzheimer’s disease.
Hyperactive immune system
Hyperactive immune system is a hallmark of Down syndrome. This condition protects those with Down syndrome from certain cancers but can also lead to chronic inflammation.
Espinosa states, “And of significance to Alzheimer’s,” that “they have brain inflammation throughout the lifespan.”
Evidence is mounting that brain inflammation plays a key role in Alzheimer’s. Espinosa is working with a group of researchers to find ways to maintain the brain’s immune system under control.
He says that clinical trials are being conducted for immunomodulating agents for Down syndrome. “There is an active study right now to reduce that response with a group of drugs called JAK inhibitors.”
JAK (Janus Kinase) inhibitors can be used to reduce inflammation in patients with rheumatoid and other autoimmune conditions.
Espinosa believes these drugs will also reduce inflammation in brains and lower the risk of Alzheimer’s. He is currently testing the approach with people with Down syndrome.
Extra chromosome, extra amyloid
The Crnic Institute has another team that is trying to modulate the immune system.
Dr. Huntington Potter explains that the goal is to increase an immune cell that “eats up things that aren’t supposed to exist.”
Amyloid is a sticky, toxic substance found in Alzheimer’s patients’ brains. Because Down syndrome patients have an extra chromosome that contains genetic instructions for making the substance, they tend to have higher levels of amyloid in their brains.
Potter hopes to stop this by using a drug called Leukine that increases the immune cells that eat amyloid.
He did a small study last year to determine if Leukine can be safely given to patients with Alzheimer’s.
He says, “We didn’t expect to see a cognition benefit.” “But after three weeks of Leukine treatment, the individuals saw a significant improvement in their cognition.
These people didn’t have Down syndrome. Potter’s team demonstrated that Leukine can also be used in Down syndrome mice in March.
He says, “That allowed us to apply to a grant to study young people with Down syndrome before it becomes Alzheimer’s disease.”
The National Institute on Aging awarded them a $4.6 million grant. They now need to recruit young adults with Down syndrome to participate in the study.
Lina Patel, director at the Crnic Institute, said that this shouldn’t be an issue.
She says, “The self-advocates we work with are really proponents of research.” They see how it directly impacts their lives, and those of others.
