Scientists reverse Alzheimer’s in middle-aged mice

Scientists have successfully reversed Alzheimer’s in a middle-aged lab mouse – using the same method as a major clinical trial in humans which was called off yesterday.

The team at Cleveland Clinic admitted they were ‘shocked’ when their attempts to reduce amyloid plaque in mice completely eradicated the dangerous build-ups that slowly cripple the brain. 

They claim their tests on a 20-month-old mouse – equivalent to a 50-year-old human – show it could be possible to halt the disease if it is caught decades earlier than usual. 

Lead author Riqiang Yan envisions a future when these enzymes, known as BACE1 inhibitors, could be available as a vitamin that all humans take preventatively to stave off neurodegenerative disease.

However, just hours before Yan’s paper was published today, Merck announced it had pulled the plug on its phase 3 clinical trial in late-stage Alzheimer’s patients using this same inhibitor after an interim review found more risks than benefits.

Already aware of the Merck failure, Yan told Daily Mail Online last night that he still believes BACE1 is the answer to preventing and treating Alzheimer’s.

The Cleveland Clinic team admit they were ‘shocked’ by the clear-cut result using the same drug as Merck’s phase 3 clinical trial in humans which was called off yesterday

‘We were surprised it worked so well, we saw complete reversal,’ Yan, who will start as chair of the department of neuroscience at the University of Connecticut this spring, said.

‘To our knowledge, this is the first observation of such a dramatic reversal of amyloid deposition in any study of Alzheimer’s disease mouse models.’   

BACE1 helps produce beta-amyloid peptide by cleaving amyloid precursor protein. 

Drugs that inhibit BACE1 are therefore being developed as potential Alzheimer’s disease treatments.

However, because BACE1 controls many important processes by cleaving proteins other than APP, these drugs could have serious side effects. In many trials, mice completely lacking BACE1 suffer severe neurodevelopmental defects.

To investigate whether inhibiting BACE1 in adults might be less harmful, Yan and colleagues generated mice that gradually lose this enzyme as they grow older. To their surprise, the mice developed normally and appeared to remain perfectly healthy over time.  

‘If we can show the compound is safe, it would be available for preventative measures.

‘BACE inhibitors can function like a vitamin, you could give it out to people early on and people could take it comfortably for years.

‘Our tests on a 20-month-old mouse found no side effects, now we have to look at a much older mouse to see if this can work in later stages of disease.’    

The findings could be a game changer for the pharmaceutical industry, which has had a rough ride with BACE1 inhibitors – although some analysts claim Merck’s failure suggests we are barking up the wrong tree. 

On Tuesday, Merck announced in a statement that it has pulled the plug on a trial with patients given either a placebo, or 12mg or 40mg of verubecestat, once a day.

Roche did away with BACE1 inhibitors in 2013. 

Eli Lilly also dropped the method in 2013, but a year later joined forces with AstraZeneca to try another version in early-stage patients, a similar age to the mice tested in Yan’s new study. That is now in phase 3 clinical trials. 

Biogen and Eisai are also in advanced clinical trials testing a similar but subtly different BACE inhibitor – E2609 – in early-stage patients.

Meanwhile, Amgen and Novartis are testing a BACE inhibitor known as CNP520, which they are testing on people at-risk of Alzheimer’s, to see if it could work preventatively. 

The race has been high-powered and fast-paced for years, but with so many trials in late stages – and Merck’s most promising trial now out of the question – there is palpable excitement at who will be the next front-runner to score the jackpot and make a fortune.   



Read more at DailyMail.co.uk