The protein, known as 'transthyretin' appears to protect brain cells by intercepting the toxic protein and preventing it from interacting with the brain tissue.The researchers are hoping this discovery could lead to patients with a genetic predisposition to Alzheimer's disease could take an as yet undeveloped drug to increase transthyretin protein and prevent the disease from developing.
Theoretically, the drug also could be given in the early stages of Alzheimer's to stop progression of the disease, preserving a higher level of cognitive function in patients.
Unlike current drugs for the condition, which only try to prop up the impaired cognitive and memory systems in Alzheimer's sufferers, A transthyretin-based drug would tackle the underlying mechanisms behind the disorder.
Scientists would be aiming to fulfil three criteria in research for a viable treatment. The drug would need to be able to remove the 'bad protein', beta amyloid, which deposits as plaques in the brains of Alzheimer's sufferers. Secondly, the drug has to be able to re-establish the functions of, and mutual communication between, neuronal cells. Thirdly, it has to improve memory and learning abilities. Currently, no drug on the market even comes close to satisfying all three criteria.
Alzheimer's disease progresses when a toxic protein, known as 'beta-amyloid,' attacks the brain's nerve cells involved in learning and memory. The beta-amyloid creates sticky plaques and tangles that gradually disable nerve cells, producing memory loss.
Dr. Jeff Johnson, lead author on the study said: "We know that the disease process depends in large part on the delicate balance between the 'good' transthyretin protein and the 'bad' beta-amyloid protein."
"In Alzheimer's patients, the 'bad' proteins significantly outnumber the 'good' proteins."
Johnson discovered the effect of transthyretin while studying mice genetically engineered with defective genes taken from human patients with early-onset Alzheimer's disease. As expected, the defective genes produced mice with higher-than-normal levels of the toxic beta-amyloid protein. These mice did not, however, exhibit symptoms of Alzheimer's disease.
Dr. Thor Stein, first author of the study, then analyzed the brains of mice and noticed that the levels of transthyretin had increased dramatically. When Stein treated the mouse brain with an antibody that prevented transthyretin from reacting with the beta-amyloid protein, the mice showed brain cell death.
The researchers concluded that the transthyretin must have protected the brain cells from the toxic effects of the beta-amyloid toxic proteins.
Test tube studies with cultured brain cells from human cortex support the findings. When Stein treated human brain cells with the transthyretin protein, then exposed the cells to the toxic beta-amyloid, the brain cell death was minimal. "Now that we have demonstrated that this protective mechanism is relevant to humans, we can start to identify strategies to slow nerve degeneration in Alzheimer's patients," says Johnson.
The results bring the likelihood of a drug to boost transthyretin a step closer. This could involve increasing the levels of transthyretin within the brain or by methods depositing transthyretin into the brain.
The resulting drug would be unique, as it would focus on preventing the loss of the brain cells instead of treating the resulting symptoms.
The transthyretin discovery will likely impact the screening of environmental chemicals for their potential role in causing or exacerbating Alzheimer's disease. The prospect of researchers developing tests that determine whether a particular chemical or agent in the environment is able to shift the delicate balance between the 'good' and 'bad' proteins is very real.
"This would allow scientists to establish definitive links between environmental exposures and Alzheimer's disease pathology," commented Johnson.
There are an estimated 18 million people in the world with dementia, according to the charity Alzheimer's Disease International, which estimates that by 2025 this figure could increase to 34 million. And finding a treatment that could delay onset by just five years could reduce the number of individuals with Alzheimer's disease by nearly 50 per cent after 50 years.
With increasing patient numbers and the limitations of available therapies, the Alzheimer's disease (AD) market is an attractive investment with huge unmet need. Although it occupies a small share of the total CNS market it is currently experiencing massive growth. Alzheimer's disease market in the seven major markets is worth $4.7 billion (€3.8 billion) and will increase to $6.1 billion by the year 2005 and $ 7.8 billion by the year 2010.
A study by Research and Markets predicts that over the next five years, acetyl cholinesterase inhibitors will continue to dominate the market, but Forest's Namenda, an NMDA receptor antagonist, will gain market share as a combination product.