Cautious optimism for new Alzheimer treatment

Cautious optimism for new Alzheimer treatment
Medical Matters

The fight in the battle against Alzheimer’s got some positive news last month when the results of a drug trial raised hope and promise for a potential new ground breaking therapy.  Disappointedly, the search for new medicines to treat Alzheimer’s has been a story of gloom and failure spanning more than 15 years when the last treatment was brought to market.

Indeed, there are currently only two medications which can help in Alzheimer’s though their effect is small and not all patients benefit. They also only act to correct the effect of neurotransmitter imbalances in the brain without slowing down disease progression.

Despite dozens of trials, none have resulted in any clinical improvements with negative studies nearly becoming par for the course. That’s why the announcement that the company Biogen are planning to submit their new drug Aducanumab to the FDA next year for approval for early Alzheimer’s was gladly welcomed albeit with caution.

But is this another false hope or should we be optimistic? After all, several other similar drugs failed to deliver results and the initial study findings for Aducanumab were also negative.

The hallmark of Alzheimer’s is the build-up of two abnormal proteins in the brain (amyloid and tau) which aggregate into plaques and tangles. While only initially affecting brain areas important in making new memories, as it spreads causing more damage it results in the devastating effects of Alzheimer’s.  Studies suggest that these changes may even begin to occur up to 15-20 years before any clinical signs emerge but nobody really knows why it happens.

Drugs trials to date have largely focused on trying to reduce amyloid build-up in the brain in Alzheimer patients. Indeed, the drug Aducanumab is an antibody that binds to amyloid in an attempt to reduce its accummulation and hence slow down the disease.

In essence, high dose treatment showed a reduction in clinical decline by between 23-27% as well as a 40% drop in functional loss as measured by study scales.”

Researchers studied the effects of a monthly infusion of Aducanumab given to those with very early Alzheimers’s in two studies each involving just over 1500 patients. While a preliminary analysis predicted study failure, additional data that become available (after the study was stopped) and included about 2000 patients who had a full 18 months of treatment had positive findings.

In essence, high dose treatment showed a reduction in clinical decline by between 23-27% as well as a 40% drop in functional loss as measured by study scales.  Brain imaging also showed a significant reduction in amyloid plaque burden making this the first ever study coupling amyloid clearance with a reduction in the clinical decline of Alzheimer’s.

However, findings were significant in just one of the two studies with Aducanumab, whereas only a positive trend was identified in the other. But two different drug doses were used and a larger proportion of patients in the negative study were on the lower dose. Furthermore, in a subset treated with the higher dose the results appear to be positive.

The findings are to be taken with some caution as similar drugs in past trials that reduced brain amyloid failed and there were also some inconsistencies in some of the study’s outcome measures. It also hasn’t been published in a peer reviewed journal and more details are awaited. For a while, trying to reduce amyloid in the brain was also felt to be dubious as it may have been a marker of other problems rather than the primary pathology.

Despite this, there is a real prospect that Aducanumab might be approved for use next year in the US though a further trial may be needed to substantiate the results first. Of interest, this study enrolled people with very early Alzheimer’s (some even pre-dementia) who ordinarily would not have been diagnosed but for sophisticated tests not widely available.

The implications of any drug that could slow down Alzheimer’s (where the average life expectancy is about 7-10 years) couldn’t be overstated. With the advent of tests to pick up disease earlier, instituting a therapy that could even slow down the rate of decline modestly would be huge.

Research is also underway to develop blood tests that might pick up preclinical disease. At present cerebrospinal fluid (CSF) testing can be used to help diagnose Alzheimers’s at a very early stage with negative testing also indicating a very low risk of disease in the short to medium term.

On a positive note too, the age at which Alzheimer’s develops has increased in the West. It is often asked is there anything that can be done to try and prevent it. For some, genetic factors increase the risk such as having two first degree relatives with the disease. But studies also consistently point to lifestyle factors. High blood pressure, obesity, diabetes, lack of exercise, poor education, smoking and depression all increase risk – probably because they impact negatively on brain function  and might even trigger changes in midlife.

To conclude, there is a realistic hope that the landscape for the treatment of Alzheimer’s may change radically in the next few decades.