Alzheimer's Are we on the right path to new drugs?

With the number of people living with Alzheimer’s disease expected to almost triple by 2050, the race is on to find a treatment that can prevent or slow the condition. But last week saw another crack emerge in the already rocky path toward an effective Alzheimer’s medication; pharmaceutical giant Eli Lilly announced the failure of what had previously been hailed a “breakthrough” in the treatment of the most common form of dementia.
(Alzheimer’s disease is a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. A neurodegenerative type of dementia, the disease starts mild and gets progressively worse.)

In a statement released last Wednesday, Eli Lilly revealed that their drug solanezumab failed to slow cognitive decline in a phase III clinical trial of more than 2,000 patients with mild Alzheimer’s disease.
Solanezumab is a monoclonal antibody that aims to slow Alzheimer’s progression by targeting and breaking down beta-amyloid plaques in the brain, which are clumps of protein thought to play a significant role in the disease.

While there are a number of other drugs in development that work in a similar way, none had come as far as solanezumab; it is the first medication of its kind to reach the last stage of testing prior to being eligible for license application, and researchers were optimistic that the drug would yield success.

I n 2012, early data from the trial suggested solanezumab could slow disease progression by around 34 percent for a subset of patients in the earliest stages of Alzheimer’s.
And last year, Medical News Today reported on further results from the trials that revealed the earlier solanezumab is given to patients with mild Alzheimer’s, the greater the chance of success.
Beta-amyloid and Alzheimer’s
Beta-amyloid is a “sticky” protein fragment produced by a molecule called amyloid precursor protein (APP). Beta-amyloid can accumulate between nerve cells - or neurons - in the brain, clumping together to form so-called plaques.

According to the National Institute on Aging, some individuals will develop these plaques as they age, but they are much more abundant in certain regions of the brain in people with Alzheimer’s disease, including the hippocampus - the region associated with learning and memory.
As such, beta-amyloid is considered a hallmark of Alzheimer’s disease. However, precisely how it contributes to the condition is a topic of debate.
In fact, scientists remain unclear about whether beta-amyloid plays a role in the development of Alzheimer’s disease, or whether it is a byproduct of Alzheimer’s pathology. In other words, is beta-amyloid a cause or a symptom of Alzheimer’s?

The former is the more widespread theory. A study published in 2013 in the journal Science, for example, used mouse models to show how beta-amyloid destroys the connections between brain cells - called synapses - before forming plaques to cause nerve cell death.
However, other studies have suggested a protein called tau - which forms twisted strands known as “tangles” inside nerve cells - may be a primary cause of Alzheimer’s.

One such study - published earlier this year in the journal Science Translational Medicine - found that a greater abundance of tau in the brain’s temporal lobe was linked to poorer memory.
While Alzheimer’s researchers have increasingly looked to tau as a target for new drugs in recent years, the focus is still very much on beta-amyloid. But given the number of beta-amyloid-targeting drugs that have failed in testing, optimism for these types of medication is gradually dwindling.