More than six years after reporting on their discovery of the striking effects a cancer-recovery drug has on mice with Alzheimer’s disease, Huntington Potter and Tim Boyd finally have the opportunity to test its long-term impact on real patients. A two-year, $1 million grant from the Alzheimer’s Association, announced on Aug. 3, is paving the way.
Potter and Boyd are PhD scientists with the Rocky Mountain Alzheimer’s Disease Center (RMADC) at the University of Colorado, which Potter leads. The drug is called Leukine, and in the research that led to the discovery published in 2010, they and colleagues found that Leukine spurred the Alzheimer’s mice to clear their brains of 55 percent of disease-associated amyloid beta plaques – and that the mice’s cognition returned to normal.
Leukine is a growth factor protein. The U.S. Food and Drug Administration approved it in 1995 to stimulate the production of white blood cells and fortify the weakened immune systems of bone marrow transplant patients. In the case of the Alzheimer’s mice, the white blood cells attacked and cleared out the amyloid plaques. But also, Boyd says, Leukine “has been known in models of stroke to regrow blood vessels. It prevents neurons around an infarct from dying, and is a growth factor for neural stem cells.”
And indeed, that’s what may have happened with the mice. Potter’s laboratory is investigating whether Leukine stimulates the development of new blood vessels and brain cells to fill the voids the plaque had left behind. If the same thing happens in human patients, it could address a big problem with other experimental drugs that clear out amyloid beta plaques without addressing the voids. Those gaps lead to serious problems, including swelling in the brain and microhemorrhaging, that have been so common among other experimental amyloid beta-reducing therapies that they have their own acronym: ARIA, for amyloid-related imaging abnormalities.
The new trial, slated to start in October, will involve 42 patients with mild to moderate Alzheimer’s disease. Twenty-eight will receive daily Leukine injections for six months, while 14 will get a placebo over the same period. The team decided to give the drug to more than the typical one-half of the cohort because, as Potter put it, “it’s much nicer to be recruited into a clinical trial that lasts that long when you have a two-thirds chance of getting the drug.”
The RMADC team will perform many tests on participants during those six months and for 45 days after the treatment course ends. They’ll check on the brain’s use of glucose (Alzheimer’s disease slows consumption of this brain fuel); do PET scans to check on Leukine-driven removal of amyloid beta plaque; and do MRIs to see if the brain is decreasing in size or not (Alzheimer’s disease shrinks the brain) and to check on ARIA-related edema and microhemorrhaging. They’ll also perform standard blood tests and electrocardiograms to make sure the immunologic reaction to Leukine isn’t causing damage to the heart or elsewhere in the body.
Much of the testing will fall to Jonathan Woodcock, MD, clinical director of the RMADC and the Memory Disorders Clinic at University of Colorado Hospital. Woodcock will also help recruit patients via the clinic. In addition, Brianne Bettcher, PhD, who leads the RMADC’s neuropsychology research team, will perform cognitive assessments on patients.
Potter’s is one of four research teams – the others are in California, Florida and Spain – receiving $1 million awards through a $7 million grant fueled by an Alzheimer’s Association partnership with Silicon Valley philanthropist Michaela “Mickey” Hoag. The team with the most compelling results will get the final $3 million to continue their investigations.
Years of prep
Potter and Boyd have been laying the groundwork for the new Leukine trial for years. 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 “significantly greater improvement in total neuropsychological function” than those treated with a different immune-system booster, and they performed better than they had in baseline testing, too.
“It had nothing to do with Alzheimer’s disease or amyloid,” Potter said. “So there may be a general benefit.”
In 2014, Potter and Woodcock launched a trial to assess the safety of Leukine in Alzheimer’s patients taking the drug for three weeks – the standard course for bone marrow transplant patients. Woodcock says nothing they’ve seen in the roughly dozen patients who have participated contradicts the drug’s 21-year history of safety.
Alzheimer’s, a disease afflicting 5.5 million people in the United States, has a long history of leaving promising therapies broken under its wheels. Potter, Boyd and Woodcock, keenly aware of this, will let Leukine succeed or fail with Alzheimer’s patients and report what they find. Still, they are hopeful.
“We’re a little prejudiced, but it has many benefits that no other drug has,” Potter said.
For more information on participating in the Leukine phase 2 clinical trial, register via the Alzheimer’s Association’s TrialMatch program or call (800) 272-3900.