Two battles won in war against Alzheimer disease

By the end of this year, an estimated 97,000 new cases of dementia will have been diagnosed, and an estimated 435,000 Canadians over the age of 65 will have Alzheimer disease and related dementia, according to the Alzheimer Association of Canada. By 2011, that number will have soared to more than 750,000.

What’s more, Alzheimer disease — a progressive, degenerative disease marked by the shrinkage or disappearance of brain cells — comes at an economic cost. About $5.5 billion a year is spent on people with Alzheimer’s and related dementia in Canada.

The annual societal cost of care per individual with this condition — including nursing homes, medications, community support service and unpaid caregiver time — is estimated to be between $9,451 and $36,794.

So, two new pieces of research bring new hope for people suffering from dementia and those close to them.

The first discovery was of a protein, TMP21, that is naturally expressed and seems to control the progression of the protein amyloid beta-peptide, levels of which correlate with the severity of dementia, even early in the disease. The TMP21 in individuals with Alzheimer disease is either being overproduced or malfunctioning — the scientists have yet to figure that out. But identifying the role this naturally occurring molecule has to play in the synthesis of the toxic amyloid beta-peptide, as University of Toronto researchers did this spring, is significant because it opens up the possibility of developing a drug that could mimic TMP21’s anti-toxin effects.

Shortly after news of TMP21 hit the streets, another University of Toronto scientist took a major step forward in Alzheimer’s research. Dr. JoAnne McLaurin, associate professor at the Centre for Research in Neurogenerative Disease, discovered the important function of AZD-103, a small molecule that, when given to mice models orally before they have Alzheimer disease, can prevent the cognitive deficits and the accumulation of amyloid beta-peptide. The molecule, whose discovery was 12 years in the making, combines in the brain with the amyloid beta-peptide such that the latter loses its toxic properties.

This drug is remarkable for a couple of reasons, McLaurin says. For one, it has been shown to increase the survival of mice. This is noteworthy for Alzheimer disease patients who, once diagnosed, have an average remaining life span of between eight and 10 years.

And the cognitive deficit of mice who were allowed to develop the disease before the administration of this molecule was completely restored with AZD-103.

How that would translate to humans, McLaurin says, isn’t clear. Mice are “imperfect models” in that their neurons only ever get injured; they don’t die, as they do in human sufferers of Alzheimer disease.

“Once the neurons are dead, this drug won’t help,” says McLaurin. “But what we’re hoping is, if this is given to an Alzheimer’s patient, the memory loss and cognitive deficit would stop at that point and halt the disease progression.”

And AZD-103 has plenty of preventative potential for individuals who are at risk of developing Alzheimer’s because of their family history.

“I don’t like to use the word ‘cure’,” McLaurin says. “But I always say that I’m cautiously optimistic that AZD-103 will stop this disease’s progression.”

AZD-103 is in Phase 1 clinical trials in Canada. By 2010, McLaurin says, “Alzheimer’s patients could be benefiting from these drugs.”

In some ways, McLaurin admits, AZD-103 and TMP21 are addressing the same question. But one doesn’t cancel the other out at this early stage of discovery.

“We won’t stop any research because we won’t know until 2009 or 2010 whether AZD-103 really works in humans.”

The pair of these remarkable discoveries is worth celebrating, she says: “Now we know we should be targeting either the production or the clearance of this amyloid beta-peptide.

“We now know that the role it plays in the degeneration of patients’ brains is one of the defining factors of Alzheimer disease.” IE

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