This Alzheimer’s Drug Repairs Alcohol-Induced Brain Damage in Rats

A study on rats has shown a drug commonly used to treat cognitive decline in patients with dementia also reverses the neurological damage caused by bouts of excessive drinking.

While there’s still a lot to be learned about the negative effects of excess alcohol on adolescent brains, the drug could provide a reprieve from the hangovers of our misspent youth.

Donepezil is a pharmaceutical usually prescribed to reduce the confusion and memory loss caused by conditions such as Alzheimer’s disease.

Exactly how it manages this isn’t clear, but it is known to stop an enzyme called cholinesterase from producing a certain class of neurotransmitter in the brain.

Studies on adolescent intermittent ethanol exposure (AIE, or teen binge drinking to you and me) have suggested getting drunk several nights a week reduces those enzymes in certain areas of the adolescent brain.

What’s more, it’s an effect that could last well into adulthood.

A team of US researchers have put two and two together to discover donepezil might also be useful in undoing the nerve damage caused by AIE.

“Clinical studies are starting to show that adolescents who drink early and consistently across the college years have some deficits in learning and memory,” says the study’s senior author Scott Swartzwelder from Duke University.

“It’s not a sledgehammer – it’s not knocking their memory out completely – but there are demonstrable, if subtle, effects on their cognitive function.”

There’s no shortage of willing test subjects researchers could call on inside university campuses to sink shots three to four times a week in the name of science, even if it did end in an autopsy.

Thanks to a little thing called ‘ethics committees’, they were forced to use rats instead. Not quite as informative as human models, but at least they didn’t have to arrange for designated drivers.

For just over two weeks, a bunch of 30-day-old rats either got moderately sloshed on ethanol every other day or so, or stayed nicely hydrated on distilled water.

They then had a break from all that partying for a further 20 days before being divided into two groups, each made of a mix of binge-drinking and teetotalling rats.

One half was then treated with donepezil for four days, the other given plain water, before their brains were analysed.

Adult rats that were frequently exposed to moderate levels of alcohol as ‘teens’ had fewer branches called dendritic spines emerging from their neurons.

“Any change in the density of spines on dendrites tells you those cells are processing information differently than they should be, and whether that processing goes up or down can be a problem,” says Swartzwelder.

That wasn’t the case in the alcohol-dosed rats treated with donepezil, whose dendritic spines seemed just fine.

On further digging, the researchers found a gene called Fmr1 was involved. Changes to this gene have been implicated in a range of mental health conditions, from Parkinson’s disease to autism and various other forms of learning difficulty.

Its products usually play a key role in communication between neurons, so finding the gene’s expression was also being impacted here is perhaps no surprise.

Donezepil didn’t just reverse the structural damage to the nerve’s branches; it undid the effects of alcohol on regulation of Fmr1.

Given teenagers have been drinking themselves silly since humans first found booze in yeast-infected fruit juice, you might think we’d know more about the effects of AIE.

Not so.

“Studies in humans of the long-term effects of drinking during adolescence are just beginning to emerge,” says Swartzwelder.

“But the data we do have indicate negative cognitive effects, and this puts us one step closer to one day being able to reverse those.”

We could also just tell teenagers not to binge drink. Given what little we do know about the brain damage it causes, not to mention that 16% of drinkers engage in binge drinking, it has the potential to be a massive health problem.

We shouldn’t rely on medicine coming to the rescue, of course. But it’s good to know somebody is thinking about the effects.

This research was published in Alcoholism: Clinical and Experimental Research.

Alzheimer’s drug targeting soluble amyloid falls short in a large clinical trial : NEJM

End of fillings in sight as scientists find Alzheimer’s drug makes teeth grow back

A dental gum examination
The days of fillings could be over after scientists find a drug stimulates stem cells in teeth

Fillings could be consigned to history after scientists discovered that a drug already trialled in Alzheimer’s patients can encourage tooth regrowth and repair cavities.

Researchers at King’s College London found that the drug Tideglusib stimulates the stem cells contained in the pulp of teeth so that they generate new dentine – the mineralised material under the enamel.

Teeth already have the capability of regenerating dentine if the pulp inside the tooth becomes exposed through a trauma or infection, but can only naturally make a very thin layer, and not enough to fill the deep cavities caused by

<img src=”/content/dam/science/2017/01/09/ss-composite-image-2017-1-9-11-25-small_trans_NvBQzQNjv4BqqVzuuqpFlyLIwiB6NTmJwfSVWeZ_vEN7c6bHu2jJnT8.png” alt=”An image showing repair after four weeks (left) and six weeks (right)” width=”320″ height=”200″ class=”responsive-image–fallback”/> An image showing repair after four weeks (left) and six weeks (right)
An image showing repair after four weeks (left) and six weeks (right)

But Tideglusib switches off an enzyme called GSK-3 which prevents dentine from carrying on forming.

Scientists showed it is possible to soak a small biodegradable sponge with the drug and insert it into a cavity, where it triggers the growth of dentine and repairs the damage within six weeks.

The tiny sponges are made out of collagen so they melt away over time, leaving only the repaired tooth.

This is an extremely interesting and novel approach which shows great promise and we will look forward to it being translated into clinical applicationDr Nigel Carter, CEO of the Oral Health Foundation

Professor Paul Sharpe, lead author of the study, of the Dental Institute, from King’s College London, said: “The simplicity of our approach makes it ideal as a clinical dental product for the natural treatment of large cavities, by providing both pulp protection and restoring dentine.

“In addition, using a drug that has already been tested in clinical trials for Alzheimer’s disease provides a real opportunity to get this dental treatment quickly into clinics.”

Currently dentists use man-made cements or fillings, such as calcium and silicon-based products, to treat larger cavities and fill holes in teeth.

But this cement remains in the tooth and fails to disintegrate, meaning that the normal mineral level of the tooth is never completely restored.

However the new technique could reduce the need for fillings of cements, which are prone to infection and often need replacing a number of times.

When fillings fail or infection occurs, dentists have to remove and fill an area that is larger than what is affected, and after multiple treatments the tooth may eventually need to be extracted.

Dr Nigel Carter, CEO of the Oral Health Foundation: “This is an extremely interesting and novel approach which shows great promise and we will look forward to it being translated into clinical application that could undoubtedly be a progressive step in the treatment of dental disease.

“While fillings have remained highly effective in repairing large cavities, they are susceptible to wear-and-tear and can occasionally be in need of repair and replacement. This presents problems as the dentist could have to remove and fill a larger area each time and after numerous treatments the tooth may then have to be extracted.

“Creating a more natural way for the tooth to repair itself could not only eliminate these issues, but also be a far less invasive treatment option for patients. With dental phobia still being very common, using a natural way to stimulate the renewal of dentine could be an especially comforting proposal for these groups, for which undergoing treatment can often be a cause great anxiety.”

The procedure has so far only been used in mouse teeth, but it was shown to ‘fill the whole injury site’.

And Tideglusib has already been shown to be safe in clinical trials of patients with Alzheimer’s disease so scientists say that the treatment could be fast-tracked into dental practices.

New Alzheimer’s drug trial clears toxic brain proteins and slows memory loss.

A new drug trial for Alzheimer’s patients has just been completed, and researchers are calling the results the most promising yet in the fight against the disease.

The drug targets amyloid deposits – toxic proteins linked to the onset of Alzheimer’s – and after just 12 months, patients on the highest dose had no detectable signs of these deposits.

Not only that, but for the 20 early-stage Alzheimer’s patients who took the highest dose of the drug for more than six months, there were indications that their cognitive decline and memory loss had been slowed down.

“This is the best news we’ve had in my 25 years of doing Alzheimer’s research, and it brings hope to patients and families affected by the disease,” one of the researchers, neurologist Stephen Salloway from Butler Hospital in Providence, Rhode Island, told Nature.

“Compared to other studies published in the past, the effect size of this drug is unprecedented,” another of the team, Roger Nitsch from Zurich University, Switzerland, told The Independent.

Before we go into the details, let’s be clear that this is just one trial with a small number of participants, and “cautiously optimistic” is the name of the game here.

Nothing is confirmed until the results are replicated in a much longer trial with a larger and more diverse sample set, so while we can be excited about the incredible potential of this drug, we need to wait for follow-up trials.

So with that in mind, here’s what happened.

The team recruited 165 participants who had been diagnosed with the early stages of Alzheimer’s disease to test the efficacy of a drug based on an antibodycalled aducanumab.

Aducanumab has been shown to naturally occur in people who age without experiencing significant cognitive decline, so the researchers decided to see what would happen if they injected high doses of the antibody into people with early-stage Alzheimer’s.

It’s not clear how this antibody works, but the team announced at a recent conference that it appears to target amyloid deposits in the brain, but not in the bloodstream.

“The hypothesis suggests antibodies that attack amyloid in the bloodstream get sidetracked and never make it into the brain,” Karen Weintraub explains over at Scientific American. “By focusing on brain amyloid, aducanumab seems to be able to cross into the brain to reach its target.”

The 165 participants were split into different groups, and some received the aducanumab drug in different doses, and one group of 40 received a placebo.

Of the 103 patients who were given the drug once a month for up to 54 weeks, they all experienced a reduction in the amount of amyloid deposits in their brains. And the researchers found that the higher the dose, the more deposits were cleared from the brain.

In the group of 21 patients who received the highest dose, no detectable signs of amyloid deposits remained in their brains after a year.


The red represents amyloid-beta plaques. 

Similar results were reported in a pre-trial mouse study, which saw mouse brains cleared of amyloid deposits after aducanumab treatment.

“This drug had a more profound effect in reversing amyloid-plaque burden than we have seen to date,” Alzheimer’s researcher Eric Reiman from the Banner Alzheimer’s Institute in Phoenix, Arizona, who is not involved in the study, told Erika Check Hayden at Nature.

“That is a very striking and encouraging finding and a major advance.”

No one’s entirely sure what causes Alzheimer’s disease, but it’s thought to result from a buildup of two types of lesions in the brain: amyloid deposits – or ‘plaques’ – and neurofibrillary tangles.

Amyloid deposits sit between the neurons as dense clusters of beta-amyloid molecules – a sticky type of protein that easily clumps together – and neurofibrillary tangles are caused by defective tau proteins that clump up into a thick, insoluble mass inside the neurons.

This causes disruptions to the transportation of essential nutrients around the brain, which is thought to bring on the cognitive decline and memory loss associated with Alzheimer’s disease.

Over the years, the roles of amyloid deposits and neurofibrillary tangles in the onset of Alzheimer’s have been debated, because it’s not yet clear if one causes the other, or if one has a greater overall effect.

But this new trial suggests that if you can get rid of the amyloid deposits, you have a chance at stalling the progression of the disease. The researchers report that they saw slower cognitive declines in 91 patients treated with the drug.

“Aducanumab also showed positive effects on clinical symptoms,” Nitsch explained in a press statement. “While patients in the placebo group exhibited significant cognitive decline, cognitive ability remained distinctly more stable in patients receiving the antibody.”

The results are definitely exciting, but it’s time to replicate them in a larger group of patients. The team is now recruiting another 2,700 patients from 20 different countries to participate in a new 18-month trial, the results of which are expected in 2020.

“These results are the most detailed and promising that we’ve seen for a drug that aims to modify the underlying causes of Alzheimer’s disease,” James Pickett, head of research at the Alzheimer’s Society, who was not involved in the study, told Ian Johnston at The Independent. 

“No existing treatments for Alzheimer’s directly interfere with the disease process – and so a drug that actually slows the progress of the disease by clearing amyloid would be a significant step.”

Novel Alzheimer’s drug shows promise in early trial

The investigational human monoclonal antibody drug aducanumab (BIIB037) has been shown to reduce amyloid plaque levels in the brain and slow cognitive decline in patients with early or mild Alzheimer’s disease (AD) in an early stage study.

Aducanumab was able to reduce amyloid plaque in all regions of the brain at week 26, with even greater reductions at week 54. The reduction was greater with the 10  mg/kg than the 3 mg/kg dose.

In addition, patients receiving the highest dose of the drug (10 mg/kg) had lower reductions in cognitive impairment scores (2.56 versus 3.14 points for patients on placebo) on the Mini Mental State Examination (MMSE) at 1 year, a statistically significant advantage. On the Clinical Dementia Rating (CDR) scale, another measure of cognition, patients on the highest dose of aducanumab declined by an average of 0.59 points –1.45 points lower than those on placebo.

Investigators said a difference of 1-2 points between scores is considered meaningful. The higher the aducanumab dose the patients took, the less their cognition declined, and the longer they took the drug, the bigger the difference between treated and control groups.


The study, presented at the 12th International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders in Nice, France, included 166 patients with prodromal or mild AD randomized to varying doses of aducanumab or placebo. [AD/PDTM 2015; Abstract 269]


The most common adverse event associated with aducanumab was the presence of amyloid-related imaging abnormalities (mild oedema, effusion) on MRI  in patients with the Alzheimer’s-related gene ApoE4. Fifty-five percent of ApoE4 carriers receiving the highest dose of adunucumab developed amyloid-related imaging abnormalities compared with 17 percent for non-carriers.

“This is the first time an investigational drug for Alzheimer’s disease has demonstrated a statistically significant reduction in amyloid plaques as well as a statistically significant slowing of clinical impairment in prodromal or mild disease,” said Dr. Al Sandrock, chief medical officer of Biogen, which makes aducanumab.

“Based on these results, we are advancing aducanumab to phase III trial, with plans to initiate enrolment later this year.”

Aducanumab targets beta amyloid proteins, including soluble oligomers and insoluble fibrils in the amyloid plaques which may play an important role in the development of AD, a disease which currently has no cure.