San Antonio — George Perry, a scientist at the University of Texas at San Antonio, has long proposed that drug developers and researchers need to look earlier into the roots of Alzheimer’s disease.
Over more than two decades, Perry has studied the possibility that diseases like Alzheimer’s may get their start because the body produces too many variants of oxygen, called free radicals, which cause cell damage, and not enough antioxidants to limit the damage. The process, called oxidative stress, has been associated with aging and neurodegeneration.
A potential discovery that targets the early development of the disease—in his area of research or elsewhere—may help limit incidence in a condition that’s seen little therapeutic progress in the last 30 years, he says.
“You would have a tremendous effect on Alzheimer’s disease if you could delay the disease by five years—reduce it by 50 percent,” Perry said in an interview.
That’s why Perry agreed to take a paid position on the scientific advisory board of a small San Antonio company, Phoenix Biotechnology, which has been developing a plant-based drug for cancer for more than a decade, but is now pinning its future on preliminary, preclinical data for neurodegenerative disease. In 2016, the company published findings that indicated its drug may be able to produce an antioxidant response in the brain, which followed other early results showing that the drug may stimulate a protein related to memory and learning.
Phoenix is looking for help promoting its drug in part because it is running out of time and money. Since it was founded in 2003, Phoenix has spent $22 million from private investors, who are now getting “a little long in the tooth,” says president and chief science officer Robert Newman.
Instead of seeking more private funding, the company now wants to find a larger drug developer to continue the research. Phoenix’s original cancer research is expected to produce clinical results later this year, but the firm is betting that its Alzheimer’s disease data will tip the scale in attracting suitors.
“I’m going to be 79 years old in a couple of months. I’ve been looking at this particular opportunity for a couple of years,” says Phoenix CEO Crandell Addington. “We intend to do some type of merger or acquisition so we can move this drug along, particularly in light of what we discovered in neurodegenerative diseases.”
Phoenix is facing two big hurdles, however: The data it has are limited, and Alzheimer’s drugs have a terrible track record in clinical trials. A 2014 paper spotlighted a nearly 100 percent failure rate over a decade; there have been more failures since then. In February, Merck (NYSE: [[ticker:MRK]]) was the latest to disclose a failed trial when its experimental therapy for mild-to-moderate Alzheimer’s, verubecestat, came up short. That followed another Phase 3 failure for Eli Lilly’s (NYSE: [[ticker:LLY]]) solanezumab.
The Merck and Lilly compounds focused on the prevailing theory about Alzheimer’s: the condition might be treatable with a drug that clears clumps of amyloid protein, called plaques, from the brain. Perry believes that amyloid plaques might be a consequence of the oxidative stress, rather than a signal that the disease is taking root. A debate rages on the value of targeting amyloid, and companies like Biogen (NASDAQ: [[ticker:BIIB]]) are still pursuing similar related treatments.
Other researchers, meanwhile, are taking different approaches; one in particular relates to Phoenix’s work.
In an Alzheimer’s brain, there is loss of function of synapses and neurons, the circuitry essential to short-term memory. A protein called brain-derived neurotrophic factor (BDNF) may play a key role in supporting that circuitry, according to a 2011 published by Mark Tuszynski and Alan Nagahara of the University of California, San Diego (UCSD).
People with the highest levels of BDNF had a 50 percent slower cognitive decline than those who expressed the lowest levels, according to a January 2016 study from researchers at Rush Alzheimer’s Disease Center in Chicago. Other researchers have published similar findings, but BDNF exploration is still quite early, and its role in Alzheimer’s is not fully understood.
When Phoenix was studying its compound PBI-05204 in cancer, patients who received the drug had increased levels of BDNF, the company said. But chief science officer Newman isn’t a neurologist, so he asked a researcher at Duke University, Donald Lo, to examine the implications of stimulating BDNF. Lo was already studying plant-based treatments similar to PBI-05204 in stroke victims. He wanted one that could cross the blood-brain barrier, which Phoenix’s drug can do, Newman says.
In studies published in 2011 and 2014, Lo and a research team wrote that the brains of mice in a stroke model had increased levels of BDNF after receiving PBI-05204. The researchers said the drug, which can be administered orally,
