Researchers in Abu Dhabi have made a breakthrough discovery they believe could halt or even reverse the devastating effects of Alzheimer's disease.
A team led by Dr Magzoub Mazin, an assistant professor at New York University Abu Dhabi, has designed small proteins which could be deployed to combat other harmful proteins which prove toxic to the brain.
Their potentially groundbreaking work based on cell cultures opens up the prospect of new treatments for the neurodegenerative condition.
The scientists are hoping to test out their army of 'good' proteins on mice, which could herald the beginning of clinical trials if successful.
“We did a series of experiments. The first results, when they came back, were very promising,” said Dr Magzoub, a British researcher who has worked at NYU Abu Dhabi since 2012.
Alzheimer's disease, the most common form of dementia among older adults, is a degenerative brain condition that slowly destroys memory and thinking skills and, eventually, even the ability to carry out the simplest of tasks.
In most cases, symptoms first appear when a person is in their mid-60s.
Alzheimer's disease is associated with the build-up of a protein called amyloid-beta.
These proteins are 'misfolded', meaning they do not develop into their natural shape and therefore prevent nerve cells or neurons from working properly, harming memory and other brain functions.
With a view to combating this, Dr Magzoub’s laboratory at NYU Abu Dhabi has developed particular forms of another type of protein called cell-penetrating peptides (CPPs).
The researchers showed that the CPPs could prevent amyloid-beta from accumulating in its harmful misfolded form, and could stop amyloid-beta from damaging nerve cells.
“This is the first time anybody has developed this CPP that functions as an amyloid-beta inhibitor,” said Dr Magzoub.
He said that other types of CPPs were already being used in some drug trials, where they have been delivered intravenously in a similar way to chemotherapy.
The work was carried out in partnership with the laboratories of Professor Andrew Hamilton, the president of NYU, and Professor Astrid Gräslund, at Stockholm University.
A particularly promising finding is that the CPPs appear able to deactivate amyloid-beta inside cells and to expel it from cells.
Dr Magzoub said this means that CPPs might not only halt the deterioration of people with Alzheimer’s disease, but may even be able to reverse the condition, within limits.
It might be possible to develop similar CPPs that could act against other diseases linked to amyloid proteins, such as Parkinson’s disease.
Developing the CPPs was complex work that relied upon previous studies by Dr Magzoub and others to understand how the proteins work, including what affects their ability to enter cells.
The next step is to carry out experiments on mice to find out if the effects in cell lines can be replicated in living organisms. Dr Magzoub hopes to do this work in his laboratory.
If mice studies prove successful, clinical trials with people could be considered. While it is likely these would be a number of years off, Dr Magzoub said highly promising results in mice could accelerate the process.
“Typically drug development takes a number of years and requires quite a bit of investment to go through human trials,” said Dr Magzoub.
"How long it takes would depend on how effectively it works in vivo. A lot of things work beautifully in cells but don't necessarily work well in in vivo models."
The term "in vivo" is Latin for in a living organism, and contrasts with "in vitro", which refers to things out outside living organisms, such as in test tubes or petri dishes.
Dr Magzoub said he was “optimistic” the CPPs would work well in mice, although it might be necessary to fine tune the sequence of amino acids – the building blocks of proteins – that they are made from.
“Once the paper comes out, there’s going to be a lot of interest in it. Other groups will also become interested in developing these CPPs,” he said.
“If they work beautifully in mouse models, that would motivate people to push through these studies more quickly. It would be a matter of years, but it would be shorter than if they don’t work as well as we think they do.”
The new study was published this week in Cell Reports Physical Science and entitled "Designed cell-penetrating peptide inhibitors of amyloid-beta aggregation and cytotoxicity".