A team of University of Colorado School of Medicine researchers has reported rapid improvement in cognition and self-care capabilities among patients who took a drug called leukine.
While the ongoing, early-stage study is small with a focus on safety among patients with Alzheimer’s disease, leukine has a long history: it’s a growth factor protein the U.S. Food and Drug Administration approved in 1995, and has been used ever since to stimulate white blood cell production in bone marrow transplant patients.
CU Rocky Mountain Alzheimer’s Disease Center (RMADC) scientists Huntington Potter, PhD, and Tim Boyd, PhD, are leading the ongoing research, with help from RMADC Clinical Director Jonathan Woodcock, MD, who leads the Memory Disorders Clinic at UCHealth University of Colorado Hospital. The team presented its results at the recent Alzheimer’s Association International Conference in London.
The two-year study, funded by CU, private philanthropy and a grant from the Dana Foundation, launched in October 2016. It’s a continuation of years of work focusing on the drug’s safety and effectiveness with Alzheimer’s patients. Of 32 patients enrolled through Woodcock’s clinic and the University of South Florida, 13 received daily leukine injections for three weeks, with the rest receiving placebo injections of saline solution.
When tested just 18 days in, the patients who got leukine scored better on a standard cognitive impairment test. They also fared better in surveys, filled out by caregivers, designed to establish a patient’s ability to clean, groom, feed and otherwise care for himself. Those who got the placebo saw no notable changes on either front.
“We did not expect to see an improvement in any cognitive measure in such a short period of time,” said Potter, who leads the RMADC, in an email. “The finding is preliminary and must be confirmed in a new trial, which we have received partial funding for from the Alzheimer’s Association. The University of Colorado and the Global Down Syndrome Foundation will begin in a few months.”
Based on the positive results, the subsequent study will provide leukine to two-thirds of the cohort, roughly reversing the ratio thus far, he added.
The cost of Alzheimer’s disease is staggering. The Alzheimer’s Association estimates that 5.5 million people have the disease in the United States alone, about the same as the entire population of Colorado. The association estimates the U.S. cost of care at $259 billion a year, and that doesn’t count the estimated $230 billion in unpaid care by family and others. With baby boomers heading into old age, the costs – financial and otherwise – are, without a medical breakthrough, poised to skyrocket.
If leukine turns out to be that breakthrough, Potter and Boyd will be primarily to thank. They and colleagues published work that showed mice with Alzheimer’s disease cleared their brains of 55 percent of disease-associated amyloid beta plaques after receiving leukine, and that the mice’s cognition returned to normal.
Leukine’s exact effects on the brain remain unclear, but the researchers suspect a couple of benefits. One is that, in mice, it’s a growth factor for neural stem cells. It also helps regrow blood vessels, which may be decisive, Potter and Boyd say: drugs that just clear out plaques leave voids that can induce brain swelling and microhemorrhaging. It may be that leukine’s growth-stimulation helps the brain fill the voids with new blood vessels and/or neurons, avoiding such damage.
The team’s prior leukine research extended to humans, too. They studied the cognition of bone marrow transplant patients who had taken leukine for the standard three-week course of injections. They found that, six months later, such patients showed improved cognition and function as compared to those treated only with a different immune-system booster.
In 2014, Potter and Woodcock began assessing the safety of leukine in Alzheimer’s patients who took the drug for three weeks – the standard course for bone marrow transplant patients. The Alzheimer’s patients have shown no adverse effects.
It’s been a long road to this point, and there’s still a long road ahead. The history of Alzheimer’s disease drug research is one with a prevailing theme is one of dashed hopes. Perhaps leukine will change that.
“We are cautiously optimistic and excited to start the next phase of leukine testing for Alzheimer’s disease,” Potter said.