Researchers at the University of Colorado School of Medicine have been awarded a $4.6 million, five-year grant by the National Institute on Aging to study whether a potential Alzheimer’s disease treatment is safe and effective in improving cognitive function in young adults with Down syndrome.
Huntington Potter, PhD, professor of neurology, and Peter Pressman, MD, assistant professor of neurology, are principal investigators on the study of sargramostim, which is also know by the brand name Leukine, an FDA-approved drug with nearly 30 years of safe use in numerous patient populations.
“This is the first clinical trial in years to target cognition in people with Down syndrome,” said Potter, who is director of University of Colorado Alzheimer’s and Cognition Center. “We are breaking new ground in studying both of these disorders – Down syndrome and Alzheimer’s disease. We hope that this therapy will greatly improve their quality of life.”
“People with Down’s syndrome have unfortunately been excluded from a number of previous clinical trials,” said Pressman. “I’m excited to be able to work alongside this underrepresented group of individuals.”
The grant provides funding to design and complete a clinical trial in adults with Down syndrome using sargramostim, which is a recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is used to help increase white blood cell production in some cases of medical care, including after bone marrow transplantation and after induction chemotherapy in older patients with acute myelogenous leukemia.
“We are breaking new ground in studying both of these disorders – Down syndrome and Alzheimer’s disease. We hope that this therapy will greatly improve their quality of life.” - Huntington Potter, PhD
Previous studies by Potter and his colleagues have also found that sargramostim treatment is associated with cognitive improvements in leukemia patients.
In another clinical trial, Potter and fellow researchers found that three weeks of sargramostim treatment was safe and well-tolerated in mild-to-moderate Alzheimer’s disease participants. The treatment was associated with improvement in cognition and with reduced biomarkers of neurodegeneration.
The new trial builds on this previous work and on a laboratory study in which CU researchers led by Md. Mahiuddin Ahmed, PhD, senior research instructor of neurology, and Potter found that GM-CSF reverses cognitive impairment and brain pathology in a mouse model of Down syndrome.
This award is the second grant this year awarded by the National Institute on Aging to Potter and Pressman as principal investigators on a study of sargramostim. Previously, they received a $7.5 million, four-year grant from the National Institute on Aging to study the treatment in adults with mild-to-moderate Alzheimer’s disease. In that grant, the researchers describe how patients with rheumatoid arthritis have a reduced risk for developing Alzheimer’s disease. In those cases, sagramostim is a key factor providing the protection.
This new study is focused on quality-of-life improvements for the Down syndrome community, which is particularly vulnerable. As they grow older, every person with Down syndrome develops the brain pathology associated with Alzheimer’s disease, often beginning during middle adulthood. Thanks to improved medical care, people with Down syndrome are living longer. In 1983, a person with Down syndrome lived to be only 25 years old on average. Today, the average life expectancy of a person with Down syndrome is nearly 60 years and continuing to climb.
A multidisciplinary team at CU Anschutz Medical Campus will study the safety and tolerability of the treatment. “If there is any indication that it is unsafe or not tolerated, the full trial will be stopped,” Potter said. “Safety is central to the execution of this grant.”
This new grant leverages collaborations between research teams on the Anschutz Medical Campus and demonstrates the power of working together to find innovative approaches to health care. The CU Alzheimer’s and Cognition Center team works closely with researchers at the Linda Crnic Institute for Down Syndrome, which receives substantial financial support from the Global Down Syndrome Foundation, which is based in Denver.