Is Aducanumab the Future for Alzheimer's Patients?

 by  Muhammed Sahil

It’s estimated that more than 30 million people around the world have Alzheimer’s with most aged over 65. Though there’s currently no drugs in use to cure the disease, many drugs have been developed and regularly used to manage symptoms. However this may all change soon.

Aducanumab, which is a newly developed drug for treating Alzheimer’s, was the first to be approved in 20 years. The way this drug works is by targeting the causes of Alzheimer’s. In addition the US Food and Drug administration say that there’s evidence that it reduces amyloid beta plaques in the brain and this is “reasonably likely to predict important benefits to patients.”

Beta amyloid proteins are formed from the breakdown of a larger protein called Amyloid precursor protein. Subsequently, these Beta plaques are formed from an accumulation of hard, insoluble Beta amyloid proteins that clump together between the nerve cells in the brains of patients with Alzheimer’s. These clumps are an issue as they disrupt cell function thus triggering dementia in ways including:

• Confusion 

• Communication issues 

• Memory and thinking problems 

However due to the uncertainty of the trial results, there’s been mixed feelings about the potential impact this drug has.

March - 2019

Around 3000 patients took part in the late stage international trials of the new drug. However this trial came to a close as analysis had shown that when the drug was given as a monthly infusion, it had not slowed the deterioration of memory and thinking problems than the placebo drug.

Despite this flaw, Biogen (US biotech company) analysed further data and came to the conclusion that Aducanumab does work but it just requires higher doses. Furthermore they said it largely slowed down cognitive decline.

Despite the mixed views, it’s important to know that though this is not a cure for Alzheimer’s, it’s the first treatment which tackles the destructive mechanism in the brain that leads to the destruction of Neurons, thus making this a turning point for Alzheimer sufferers.

Many scientists believe this is a major milestone that will help millions of patients but many also believe that the drug will only have small benefits. 

This drug has not been approved in the UK and even if it was it would only be limited to those who’ve had specialist brain scans to confirm their diagnosis.

The director of the UK dementia research institute expressed his approval but quoted that there were “still many barriers to overcome”.

Professor John Hardy who’s a professor of neuroscience at UCL also expressed concern saying that this drug will only help very carefully selected patients.

Professor Robert Howard was even more cautious by calling the drug’s approval a grave error. He said the FDA had ignored trial data which showed no slowing of decline in cognition or function. 

Many charities have come in support of the drug such as Alzheimer's Research UK which had even when as far as written to the health secretary asking the government to prioritise the approval process for aducanumab in the UK.

Along with these issues, it’s also been reported that 34% of all patients on aducanumab had experienced painful brain swelling and some even had bleeding in their brain.

What drugs are currently in use?

Though there’s no cure, medication is available which can readily reduce symptoms including:

Acetylcholinesterase (AChE) inhibitors:

These medicines increase levels of acetylcholine, a neurotransmitter in the brain that helps nerve cells communicate with each other.

For those with early to mid stage Alzheimer’s, there are 3 types of AChE inhibitor that can be prescribed by specialists (e.g. neurologists/psychiatrists)/GP’s who have particular expertise use in them or have been advised by a specialist

• donepezil

• galantamine

• rivastigmine 

They all work in the same way but some people will respond better to certain types or have fewer side effects including nausea, vomiting and loss of appetite.

The side effects usually get better after 2 weeks of taking the medication.

The latest guidelines recommend that these medicines should be continued in the later, severe, stages of the disease.

There's no difference in how well each of the 3 different AChE inhibitors work, although some people respond better to certain types or have fewer side effects, which can include nausea, vomiting and loss of appetite.

Memantine:

This medicine is not an AChE inhibitor.

It works by blocking the effects of an excessive amount of a chemical in the brain called glutamate.

Memantine is used for moderate or severe Alzheimer's disease and can be taken by those who can’t take AChE inhibitors.

Individuals with severe Alzheimer’s disease who are already taking an AChE inhibitor can also take Memantine.

There’s a few temporary side effects such as headaches, dizziness and constipation.

Why is it so difficult to find a cure?

Alzeheimer’s is a chronic disease which can be present 20-30 years before the first symptoms become noticeable. And so why the symptoms become noticeable, any sort of treatment may be too late to make any difference.

Even if we could diagnose it 30 years earlier, giving a potentially long toxic drug to a an individual who may or may not get the disease, raises a wide range of ethical issues.

Furthermore, trials for Alzheimer’s drugs are expensive and take years and is not as simple as developing antibiotics, in which the researchers know within a few days if the drug works.

Overall, the disagreement between the drug is evident and it may only offer false hope. For a drug that we are not sure about whether it works at all and treatment costing nearly $56,000 each year per patient, perhaps we shouldn’t take the risk.

However this could be a major turning point encouraging more research into dementia treatment which is usually underfunded in comparison to other chronic conditions e.g. cancer.