It has been a frustrating year -- a depressing decade, in fact -- for people hoping for breakthroughs in the field of Alzheimer's research and treatment.
Two pharmaceutical giants invested hundreds of millions of dollars in an intravenous drug treatment known as Bapineuzumab, which was supposed to reverse the symptoms of Alzheimer's by erasing amyloid plaque that clogs the brain as one possible telltale sign of the disease.
Pfizer and Johnson & Johnson announced in August that they were discontinuing work on the drug as a failure, after study participants in the Pittsburgh area and elsewhere got their hopes up that they were assisting in an overdue advance in battling a global increase in dementia.
The research and advocacy community then placed its hopes on Solanezumab, an alternative amyloid-fighting drug from Eli Lilly & Co. In separate announcements in September and October, the company stated its extensive trial did not produce the desired overall effects, but it did offer some potential for slowed cognitive decline among those with the mildest form of Alzheimer's. Work on that drug is to continue.
It has been a long time, though, since anyone has been able to claim success in the Alzheimer's treatment field, and even then the term "success" is best used with caution.
When the federal Food and Drug Administration approved use of Namenda to counter symptoms of the disease in 2003, it became the fifth and most recent drug marketed for the purpose. Whether it's Namenda, Aricept, Exelon, Razadyne or Cognex, however, the drugs work with variable effectiveness in different individuals and do nothing at all for some. The claims are only that in some cases they can address some of the symptoms, not that they can prevent or reverse Alzheimer's.
Pittsburgh was one of many field sites for the extensive Bapineuzumab trial, which has special hope initially because of suggestions that it might actually undo the disease's harm by attacking amyloid. Plenty of people wound up disappointed, in addition to investors.
"Everybody, patients and physicians alike, had a great deal of hope," said Oscar Lopez, a neurologist who is co-director of the University of Pittsburgh's Alzheimer Disease Research Center. "We were very disappointed with the results."
Alan Romatowski of Middlesex, Butler County, who has invited the Pittsburgh Post-Gazette to chronicle his personal journey with early-onset Alzheimer's since 2008, received Bapineuzumab infusions as a post-study participant in 2011-12, and before that he received either the drug or a placebo during the trial. In the past year, his symptoms have accelerated, although there's no way of telling if he would be worse off if not for Bapineuzumab and the daily pills he swallows of Namenda and Razadyne.
He often said he hoped Bapineuzumab was doing something for him but acknowledged he might be "whistling in the graveyard."
With the newest information, he said, "I'm not really angry, but I'm upset about the abrupt way they terminated the study. ... It's a disease that has no cure but it has hope ... but I'm not really optimistic."
Other drug trials remain in the pipeline at various stages, though Bapineuzumab and Solanezumab had jointly attracted the biggest optimism of anything in years. When neither reached its goals, it was cause for more despair in a field that deals with one of the most despairing of all diseases. It's the sixth-leading cause of death in America, and the Alzheimer's Association calls it the only one of the top 10 "without a way to prevent, cure or even slow its progression."
"Exactly how far away we are from knowing we have a treatment that will actually move us to one of these prevention schemes may or may not be years away," said William Thies, chief medical and science officer of the national association.
He said there was at least hope from Lilly's Solanezumab findings that further studies of it on mildly affected patients will provide confidence it can maintain their cognitive abilities. The question of whether amyloid in the brain causes Alzheimer's or is merely a visual manifestation of its cause by something else has been a point of debate. If Solanezumab proves effective, it would be a boon to the anti-amyloid theorists and researchers, who have been in the majority.
"That would be a major step forward in the fight against Alzheimer's," Dr. Thies said. "These results strengthen the case for testing the drug in earlier stages of the disease ... to see if the drug can prevent symptoms (a) from emerging at all or (b) from significantly disrupting the person's life."
Some of the other studies now drawing the widest attention -- with Solanezumab only fueling the interest -- are those in which participants are still functioning normally or with only mild cognitive impairment. MCI is a memory loss condition less debilitating than Alzheimer's which increases the odds the ominous disease lies ahead, although it's by no means a guarantee.
Such studies, several just getting under way, can take many years to produce results because of the slow progression of Alzheimer's. They are made easier, at least, by advances in amyloid imaging, which enable researchers to better match that potential tangible sign of Alzheimer's with the behavior of study participants as they are tested with different therapies.
Such imaging was first proved possible at the University of Pittsburgh, where professors William Klunk and Chet Mathis developed Pittsburgh Compound B to enable identification of amyloid via brain imagery about a decade ago.
Dr. Klunk, a psychiatrist who is co-director of the Alzheimer Disease Research Center, said that in the research field "many of us have already come to the conclusion that if you wait until Alzheimer's is clinically diagnosed, you've waited too long" to have any hope of attacking the disease. The future work on Solanezumab and the additional national studies getting under way could provide a path of hope someday for those in early stages, although expectations in the field have widely been tempered of late.
"It's an interesting time, but a tenuous time and scary time," Dr. Klunk said. "The fight's not over yet, but we've had 10 years now of drug trial failure since Namenda was approved. ... We'd hoped for a better signal by now."
Gary Rotstein: firstname.lastname@example.org or 412-263-1255. First Published November 26, 2012 5:00 AM