R.I. doctor sees reason for hope in hunt for Alzheimer's treatment

March 10-- Mar. 10--PROVIDENCE -- Dr. Brian R. Ott's journey to leadership in the Alzheimer's disease research and care community began with his neurology residency during the 1980s at hospitals affiliated with Harvard Medical School. In 1989, he came to Roger Williams Medical Center and what is now the Alpert Medical School of Brown University, where he remains on faculty.

Behavioral neurology -- the study and practice of human conduct and cognition -- was Ott's specialty, and that led him to Alzheimer's, which was causing increasing devastation, a toll that would only increase as baby boomers began to reach the age where risk rises.

Thirty years ago, the situation seemed hopeless.

"At that time, there were no treatments at all," Ott said. "It was a totally untreatable disorder -- but they were just starting to do clinical trials and that was really exciting as a new faculty member. So I said, 'I want to get into that. I want to study and be involved in developing drugs for Alzheimer's. It's a huge disease. It's fatal. It's common. There's a need and I can see coming down the tracks we're going to get a treatment.'"

Ott participated in the clinical trials for tacrine, which in 1993 became the first drug the FDA allowed to be prescribed for treatment of Alzheimer's memory and thinking difficulties.

"That was really exciting," Ott said. "I was really bitten once that happened, because now we had a drug approved. It was no longer an untreatable disease."

Then came more discouragement, as other drugs failed trials -- and encouragement, as researchers nonetheless made progress. Through it all, Ott's passion has never waned. After almost a decade at now-closed Memorial Hospital in Pawtucket, Ott in 2005 came to Rhode Island Hospital, where he leads the Alzheimer's Disease & Memory Disorders Center.

Once again, hope is the order of the day for Ott, his Lifespan team, and like-minded researchers and clinicians around Rhode Island and the world. While many tests of interventions to prevent or cure Alzheimer's or reverse symptoms have failed since the 1993 introduction of tacrine, new approaches could prove to be the elusive grail.

The numbers demand urgency.

Some 50 million people globally today live with Alzheimer's, which dissolves personality as it advances to certain death. An estimated 5.7 million Americans live with the disease, and it and other dementias are now the sixth-leading cause of death. The total direct cost of treatment approaches $300 billion annually, greater than for cancer or heart disease.

That new hope? At the Alzheimer's Disease & Memory Disorders Center, it stems in part from participation in the so-called TANGO national study, which is testing the tolerability, safety and efficacy of an immunotherapy drug, BIIB092, made by Biogen, for individuals age 50 to 80 experiencing early Alzheimer's or mild cognitive impairment caused by the disease.

It stems also from participation in other national studies, including "Trailblazer-ALZ," which tests the success of an antibody targeting beta amyloid protein, implicated in Alzheimer's, and "T2 Protect AD," which is evaluating the investigational drug troriluzole, a cousin of the drug riluzole, which has been shown to slow the progression of ALS. And Rhode Island Hospital, like other centers in Rhode Island, is involved in other studies.

"I feel like we're on the threshold now of getting that disease-modifying treatment or treatments," Ott said. "So I'm optimistic again."

Meeting recently with The Journal and two of his key researchers, Doctors Lori Ann Daiello and Jonathan D. Drake, Ott discussed the trials under way and his conviction, shared by many researchers, that Alzheimer's "is a disease of the lifespan that begins with genetic risk factors in birth and then in life." DNA and overall health, in other words, can play roles. And that calls for a diverse approach.

"One particular aspect of Alzheimer's disease that our group is interested in," said Drake, "is how do basic bodily processes such as high blood pressure, high cholesterol, diabetes, and these things that we call vascular risk factors -- how do these contribute to Alzheimer's disease?"

Among Daiello's specialties is the blood-brain barrier, which protects the organ's neurons and synapses from potentially harmful substances that may circulate in the bloodstream.

"The blood-brain barrier may be one of the earliest signs of the brain decompensating, and it may happen even earlier than the deposition of amyloid and tau," another protein implicated in the disease, said Daiello.

The Rhode Island Hospital scientists do not work alone; on certain research and studies, they collaborate with other scientists at the University of Rhode Island, notably Paula Grammas, head of the Ryan Institute for Neuroscience, and Butler Hospital, where Dr. Stephen P. Salloway leads the Memory & Aging Program. And with scientists out of state, as well.

"We could talk for hours about individual projects that involve working together with people in other hospitals and institutions," Ott said. "It is a network and I think it's the work that goes on between the individual researchers who make connections that moves things ahead."

-- gwmiller@providencejournal.com

(401) 277-7380

On Twitter: @GWayneMiller

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