Particles so small that they could carry drugs directly into the brain are offering a new hope for a way to stop the progression of Alzheimer’s disease, or even prevent it from happening at all.
Dementia affects around 47 million people globally, and the majority of these cases will be caused by Alzheimer’s disease. This number will reach 131.5 million by 2050, according to the World Alzheimer Report 2015.
In 10 years, more than a fifth of Europeans will be 65 years old or over.
It means that health systems will have to spend more and more resources dealing with diseases that affect elderly people, such as dementia.
By 2020, the European Innovation Partnership on Active and Healthy Ageing aims to increase the number of healthy years Europeans can enjoy by two.
Over the past decade, a handful of experimental drugs have all failed to make much of an impact on the disease, and there’s currently no way to stop the progression of the brain-wasting condition.
The particle technology, developed under a
EUR 14 million research project spanning Europe known as NAD, is one of a new breed of nano-scale treatments that hold out the promise of being able to stop Alzheimer’s disease from getting worse, or even improve the condition.
They work by passing directly into the brain and cutting away at the sticky tangles of proteins called beta-amyloids that contribute to memory loss in Alzheimer’s patients.
As part of the EU-funded project, the microscopic particles, known as nanoparticles, were injected into mice and then travelled to the brain, where they hooked onto tangled proteins. They removed around one third of them, and up to 70 % of smaller, very toxic forms. Further studies showed that the sticky stuff had left the brain.
‘After treatment for about a month, we found a strong reduction in beta-amyloid and plaques in the brain and a strong recovery in impaired memory in the mice,’ said Professor Massimo Masserini, who is leading the research from his laboratory at the University of Milano-Bicocca in Monza, northern Italy.
The secret to the success of the tiny nanoparticles is in two add-on parts. First, part of a blood protein was glued onto the particle. It acts like a key connecting to a lock in what is called the blood-brain barrier, allowing the entire particle to cross directly into the brain.
Second, a compound that is on the inside of cell membranes was added to the particle which weakens the bonds in the tangled proteins so that single molecules are released, which can then leak out of the brain into the blood.
‘Maybe if the treatment is run for longer we could completely remove the plaques from the brain (of the mice),’ said Prof. Masserini.
Last July, Prof. Masserini co-founded a company – AmypoPharma – to carry the research towards patients.
Dr David Karabelnik, a co-founder and advisor to the company through Swiss venture capital firm Breslin, believes the technology could offer a new hope for Alzheimer’s patients.
‘We have seen a number of failures by the big pharma companies in this area, often with sophisticated antibody technologies, but what is fascinating here is that this is something completely new,’ said Dr Karabelnik. ‘This is a relatively straightforward approach and it is totally different from what big pharma has been working on.’
‘Maybe if the treatment is run for longer we could completely remove the plaques.’
Professor Massimo Masserini, University of Milano-Bicocca, Italy
The technology could even offer a way to block Alzheimer’s before it develops.
‘It might even be possible to deal with early precursors of the disease and so stop real Alzheimer’s developing,’ said Dr Karabelnik’s business partner Klaus Berding, also a co-founder invested in the company and director at Breslin. It would require improved diagnostic tests for the disease to identify people in the early stages, but this is something researchers around the world are working hard at.
The team at AmypoPharma hopes to raise enough cash to begin trials on healthy people in about two years’ time, before moving on to treat Alzheimer’s patients.
‘The main aim of our spin-off company now is to find the money to test the nanoparticles out on patients,’ added Dr Francesca Re, NAD project scientist at the University of Milano-Bicocca and a co-founder of the new company.
The company is already in talks with a number of Italian venture capital groups and international investors.
‘They seem to be quite interested,’ Breslin’s Dr Karabelnik said. ‘We are looking forward to securing investments within the next four to six months to the tune of up to EUR 4 million.’
He points out that more than half of the big breakthroughs in the pharma sector are coming out of smaller companies, including university spin-offs like AmypoPharma.
The hope is that the trial results are promising enough that a partnership could be formed with a large drug company to help finance large-scale trials, and start to offer the treatment to Alzheimer’s patients.
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