The Buck Institute for Research on Aging in Novato has launched its first human clinical trial since research began at the institute in 1999 — testing the effectiveness of a drug to treat a type of cognitive impairment that often precedes Alzheimer's disease.
Stelios Tzannis, the Buck Institute's director of clinical sciences, said the institute decided to conduct the trials itself because of promising results in preclinical trials on mice. Tzannis said the drug has reversed memory loss in mice with the equivalent of Alzheimer's — not just mice with "amnestic mild cognitive impairment," which the drug is being tested on in the trial.
"After a couple of months of treatment essentially they look like normal mice," Tzannis said. "This is pretty astonishing."
The Alzheimer's Association has projected that there will be 5,861 Marin residents age 65 or older with Alzheimer's disease by 2015 and that the number will nearly double to 10,361 by 2030. The death rate for Alzheimer's disease in Marin County in 2012 was 34 per 100,000 population, compared with the statewide rate of about 31 per 100,000 population, according to the California Department of Public Health.
The institute declined to provide any details on the makeup of the drug being tested.
"We've filed a patent application," Tzannis said. "We can't disclose the exact identity of the drug."
The therapeutic has been code-named FO3 because it is a compound that binds three brain receptors involved in cognitive function. Thirty-six people are participating in the double-blind trial; 24 of the participants will receive two doses of the drug while 12 will receive a placebo.
The research is taking place in Australia, one of 48 countries excluding the United States, where FO3 has been approved for other uses.
"This is why we decided to have our clinical trial in Australia and not the U.S.," Tzannis said.
The drug's potential for treating Alzheimer's was discovered after research conducted by Dale Bredesen, who served as chief executive of the Buck Institute from the time it opened in September 1999 until February 2008. Bredesen maintains a lab at the Buck Institute, even though he now serves as director of the Mary S. Easton Center for Alzheimer's Research at the University of California at Los Angeles.
"It is extremely rewarding to have this work move into human trials — we are optimistic about this important first trial," Bredesen said in a prepared statement.
In 2008, Bredesen published the results of experiments on mice that indicated that Alzheimer's disease may result when a molecular shifting switch gets stuck in the reverse position, throwing the balance of making and breaking memories off kilter. The research indicated that beta-amyloid binds with other uncut proteins and when that happens a signal is sent that results in the death of memory cells.
"What this drug does essentially is intervene in this process, blocking the processing toward the memory loss side of things," Tzannis said. "By doing this, it helps to restore the original balance."
The trial is expected to be completed by the end of summer 2015. Tzannis said if it is successful, the next step will be an expanded trial with patients in Australia and the United States. If results continue to be encouraging, he said the U.S. Food and Drug Administration could approve FO3 for treating Alzheimer's in eight to 10 years.
Tzannis cautioned, however, that there are no guarantees.
"We've seen many, many drugs look good in clinical models that do not have the same success in humans," Tzannis said. "We have reason to believe this compound will work well in humans as well, but of course we have to prove it."
The institute said that funding for the $2 million to $3 million trial is coming from a variety of sources: the Ellen and Douglas Rosenberg Foundation, Bechtel Foundation, the Alzheimer's Association and former Buck Institute board member Hussam Abu Issa. Issa helps oversee Salam International Investment Limited, one of Qatar's largest conglomerates.
Tzannis said the institute does not plan to take the drug all the way through the development process.
"Our hope," Tzannis said, "is that pending positive results from this clinical trial we'll be able to partner with a pharmaceutical company that will take it forward into the next stage of clinical development."