Washington Editor

WASHINGTON - Retired Supreme Court Justice Sandra Day O'Connor, whose husband John was diagnosed in 1990 with Alzheimer's disease, was among those who urged Congress at a hearing Wednesday to allocate more research funding for the disease, which affects about 5.2 million Americans.

"We need to fight this killer not only in the research lab, but also at the treatment site, in the halls of government and in the communities that people with Alzheimer's call home," said O'Connor, who left the bench in 2006 to care for her husband.

"We need to move quickly," she declared. "I cannot overemphasize the need for urgency."

Despite the growing number of Alzheimer's cases, public funding for the disease has grown very little in the past five years," O'Connor said, adding that the nation has been "far too lax" in investing in new research.

"We will never succeed in tackling Alzheimer's by tweaking our existing systems or being satisfied with piecemeal, incremental changes," said the first woman justice to sit on the high court.

Sen. Herb Kohl (D-Wis.), chairman of the Senate Special Committee on Aging, which convened the hearing, noted that the Senate is considering legislation that would double the National Institutes of Health's funding for Alzheimer's disease, bringing the total to $1.3 billion.

The Alzheimer's Breakthrough Act, introduced last year by Sens. Barbara Mikulski (D-Md.), Kit Bond (R-Mo.), Hillary Clinton (D-N.Y.) and Susan Collins (R-Maine), passed the Senate Health, Education, Labor and Pensions Committee in July and is awaiting full Senate action.

Kohl said he also plans to introduce legislation that would provide funding for training and support services for family caregivers.

Lawmakers just last week introduced a bill in both chambers of Congress, known as the National Neurotechnology Initiative Act, that would provide $200 million in additional federal funds for research and discovery of treatments for brain-related injuries and illnesses, such as Alzheimer's disease. (See BioWorld Today, May 12, 2008.)

In addition to increased federal funding, O'Connor said, the nation must encourage researchers to share their insights "in real time, rather than waiting many months, or even years, until patents are filed or study results are published."

The nation needs to offer new incentives and opportunities that would bring federal researchers and drug development firms together to work collaboratively to find a cure for Alzheimer's, she insisted.

While Alzheimer's drugs currently on the market only treat the symptoms, several new therapies in clinical trials show promise of stopping the progression of the disease, Rudy Tanzi, a professor of neurology at Harvard Medical School and the director of the genetics and aging unit at Massachusetts General Hospital in Boston, told lawmakers.

Those new investigational agents work by curbing accumulation of toxic amyloid beta (Abeta) molecules in the brain, said Tanzi, whose laboratory in 1987 discovered the first Alzheimer's gene. His lab went on to identify two more genes in 1995, all three of which have been found to cause early onset Alzheimer's disease.

Firms involved in R&D for Alzheimer's disease targeting Abeta as a way of treating the condition are either trying to limit the production of Abeta, clear it from the brain or neutralize Abeta's toxic properties, Tanzi told lawmakers.

"Novel drugs of all three classes are currently in clinical trials, including a promising one that my lab helped develop over the last 10 years," said Tanzi, who founded Melbourne, Australia-based Prana Biotechnology Ltd. in 1994 as a virtual company from his Massachusetts lab.

Prana announced in February that results of a Phase IIa trial showed that the firm's experimental Alzheimer's disease compound PBT2, a metal-protein attenuating compound (MPAC), improved cognition and reduced Abeta 42, the protein associated with neuronal injury, after only 12 weeks. (See BioWorld Today, Feb. 27, 2008.)

The 250-mg dosage of PBT2 showed a highly statistically significant reduction of 60 percent in Abeta 42 in cerebrospinal fluid vs. placebo.

Prana earlier this week in an article published in the Proceedings of the National Academy of Sciences described a completely new class of amyloid-inhibiting drugs.

While MPAC compounds, such as Prana's PBT2, compete with Abeta by directly binding metal ions like copper and zinc, the new anti-amyloid compounds bind and block the actual metal binding site on Abeta, the firm reported.

Although there is reason to be optimistic about the success of the clinical trials of experimental Alzheimer's treatments currently under way, Tanzi said, "history dictates that the first drugs out of the gate are not always the best ones."

He predicted that an effective Alzheimer's treatment will ultimately be not in the form of one drug but a cocktail of different therapies.

While the most promising drugs have been made possible from the knowledge gained from the studies of the gene defects causing early onset Alzheimer's, those three genes together with one for late onset account for only 30 percent of the inheritance of the disease, Tanzi lamented.

"Imagine what we could do with the other 70 percent identified," he said.