By Jane Keller Gordon, Contributing Writer
Marlborough – There’s a good chance that you know someone whose son or daughter has Down syndrome. According to the National Down Syndrome Society, there are 400,000 cases in the United States and the number is rising. Those with Down syndrome experience medical complications, and variable cognitive deficits that affect speech, memory and learning.
Headquartered in Marlborough, LuMind Research Down Syndrome Foundation™’s (LuMind RDS™) goal is to develop treatments to improve the cognitive ability of people with Down syndrome.
One of its most exciting projects is the first-ever private-public partnership for a clinical trial in individuals with Down syndrome. Potentially groundbreaking, this research may contribute to the treatment of Alzheimer’s disease.
LuMind RDS™ initiated a collaboration among itself, AC Immune, a pharmaceutical company, and the National Institutes of Health (NIH). This group will fund a multi-year, Phase Ib clinical trial of an AC Immune vaccine targeting Alzheimer’s disease in adults with Down syndrome. Researchers from the University of California, San Diego (UC San Diego) Down Syndrome Research and Treatment Center are conducting the study.
The link between Down syndrome and Alzheimer’s—and the basis of the clinical trial—was first hypothesized in the 1980s, according to Dr. Michael Harpold, LuMind RDS™’s Chief Scientific Officer. Alzheimer’s patients were found to have mutations of a gene, amyloid precursor protein (APP), which regulates the production of A-beta, the main component of amyloid plaques. It is believed that these plaques, seen post-mortem in Alzheimer’s patients, are connected to the death of brain cells, and ultimately end of life.
Here’s the connection with Down syndrome: the APP gene is found on chromosome 21. Down syndrome is caused by Trisomy 21—three copies of the 21st chromosome, the smallest of the 23 pairs, which contains only about 300 genes. As a result, those with Down syndrome have an over expression of this gene, and produce more amyloid plaques than the general population.
“Virtually all individuals with Down syndrome have Alzheimer’s disease-characteristic amyloid plaques by their 40s… They develop Alzheimer’s at a significantly increased rate relative to the general population, and at an earlier age,” said Harpold.
An animal study conducted by AC Immune, published in 2016 in the journal,PLOS ONE, laid the groundwork for the clinical trial. Researchers found that an anti-A-beta vaccine was associated with, “… a reduction of A-beta as well as memory enhancement and prevention of neurodegeneration in the mouse model of Ds (Down syndrome),” according to the LuMind RDS™ website.
During the clinical trial, launched this year, the plan is to administer a series of the AC Immune anti-amyloid vaccine or a placebo to 24 adults with Down syndrome. The researchers will evaluate safety and tolerance of the vaccine, and the presence of antibodies to amyloid, clinical symptoms, and improvement in cognitive deficiencies among the study subjects.
In addition to the anti-A-beta vaccine study, LuMind RDS™ has contributed to a basic understanding of Down syndrome, identification of 10 possible drug targets and three possible candidate drugs, establishment of DS-Connect®, a global Down syndrome registry launched by NIH, and development of the Arizona Cognitive Test Battery, a scale to measure cognitive ability in those with Down syndrome.
The LuMind RDS™ website notes that there are limited dollars targeted to Down syndrome research. The foundation raised approximately $2.8 million this past fiscal year, of which $1.6 million dollars was spent on research and more than $750, 000 on program education. They have supported $15 million of research since 2004. As part of their fundraising effort, the foundation holds a “Run for Down Syndrome,” which can piggyback on any scheduled run.
Harpold said “We need to keep new discovery research going. We need to be able to have a continuous stream of new ideas, new approaches, and a lot of drug candidates in clinical trials. If they don’t work, we need to actively push for more. We are about creating new opportunities.”
For more information about LuMind RDS™ or to donate, contact Marly Chevrette at [email protected], or visit lumindrds.org.
Photos/submitted