A breakthrough new medical technique has unlocked “unlimited” possibilities for a range of drugs to better treat Alzheimer’s, tumours, and other brain diseases.
The scientists behind the discovery, from Imperial College London, believe that the new method – which involves ‘bubbling drugs into the brain’ – could also prevent diseases from first forming, as well as delaying brain ageing, and easing memory loss as we get older.
Most brain diseases currently have no cure – despite 55 million people living with Alzheimer’s (the most common form of dementia) worldwide. This is partly because of a structure in our brains called the blood-brain barrier (BBB). The BBB protects the neurons in the brain by acting as a wall against harmful toxins and pathogens.
But the same barrier prevents powerful medicines from reaching the places they are needed – often because the medicine molecules are too big to get past. Even the smaller molecules have a hard time getting in: according to the paper, more than 98 per cent of small molecule drugs are BBB-impermeable.
Dr Sophie Morse is a Research Fellow in Bioengineering at Imperial, and the lead author behind new research published in Nature Scientific Reports. The study reveals how Morse and her colleagues ‘broke into the brain’ by combining ultrasound and bubbles to temporarily open the BBB to allow a range of drugs through.
The breakthrough study is the first time short-wave ultrasound has been used to deliver such a wide range of drugs in a living body – in this case, in a mouse.
The novel drug delivery method could make the impact of existing medicines – like the new Alzheimer’s drugs – more effective. It could also reintroduce drugs that failed clinical trials because they couldn’t reach the brain. But it could also inspire the creation of new drugs designed to complement the new method.
“It opens up this massive door of basically unlimited options,” Morse told BBC Science Focus during the British Science Festival.
Among the limitless possibilities stemming from this breakthrough could see the method as a key way to delay ageing.
A brighter future for Alzheimer’s treatment
Long-wave ultrasound is already being used to disrupt the BBB and deliver medicine to the brain to treat brain diseases. However, long-wave ultrasound can have negative side effects, partly because it opens the BBB for a very long time (24 to 48 hours) – allowing dangerous toxins to flow into the brain.
Morse and her team realised that using ultrasound at lower frequencies puts less pressure on the immune system. They observed the barrier opening and closing in record time – 10 to 20 minutes – meaning four times fewer unwanted toxins.
So how does it work? Firstly, scientists inject bubbles containing non-harmful gases into the bloodstream. They then begin administering low-frequency ultrasound to the affected area.
When the bubbles reach this area, they expand and contract – pushing the walls of the blood vessel outwards. This creates the temporary gaps in the BBB that drug molecules can escape through – as shown in the video below.
In this new research, Morse found the method could remove Alzheimer’s plaques by 50 per cent in just two months. Without this treatment, the plaques would eventually cause memory loss by killing the neurons they envelop.
“The discovery that that the short pulses were making that difference was amazing,” Morse told BBC Science Focus. “And then the recent results, where we're seeing a difference in Alzheimer's, is fantastic. It was like, ‘Okay, we're actually going to make a difference’.”
Morse hopes that Alzheimer’s and other age-related impacts on the brain, including memory loss, will be gone by the time that current young people are old.
While the scientists conducted this initial research in a mouse body, clinical trials started in the US three years ago, and are just beginning in the UK. Morse estimates this means the method will take five to ten years to reach patients.
“I'd hope that by the time we get old we can get older in a nicer way because of this,” she said.
Further into the future, the method could even delay ageing entirely.
Breaking into the brain to delay ageing
Morse was awarded an Imperial College Research Fellowship to start her own research group 11 months ago.
The group plans to use the new technique to delay ageing in the brain.
“It sounds very sci-fi, but the theory is there and it should work. So we just need to test it and prove that it does,” Morse told BBC Science Focus.
Morse’s theory is that you could use the openings in the barrier to stimulate the brain’s immune cells. She thinks that this would alert tired cells to unwanted substances.
The process may then encourage the immune cells to shake off any plaque beginning to form, then engulf the bad material and break it down.
This could prevent Alzheimer’s – and even tumours – from forming in the first place.
In the future, Morse imagines, patients might reach a certain age where they could start having regular treatments to prevent brain disease. Treatments would take just a matter of minutes.
“The very futuristic vision is that you'd have clinics where – just like you go in and have a blood test – you could go in, sit in a chair, have a hair salon helmet put on top of your head, have a quick zap, and then continue with your shopping.”
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