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Expert reaction to study reporting the development of computer-designed antibodies for Alzheimer’s disease in nematodes

Publishing in Science Advances researchers present a computer-designed ‘antibody scanning’ strategy which generates a panel of antibodies that work on blocking amyloid buildup in a worm model.

 

Dr James Pickett, Head of Research, Alzheimer’s Society, said:

“The innovative approach taken by Dr Aprile and his colleagues tackles the issue of developing drugs for Alzheimer’s disease from a new angle, by using advanced computer techniques to design drugs that specifically block a crucial aspect of the disease process.

“Over the last 50 years, advances in antibody technology have delivered radical new treatments for a wide range of common diseases including rheumatoid arthritis, multiple sclerosis and some forms of cancer. However, we have not yet had the breakthrough we need in antibody therapies for Alzheimer’s disease. The research is still in the early stages and so far has only been tested in small worms. These antibodies will need extensive testing to find out whether they can overcome the problems we’ve seen before with drug development in Alzheimer’s. Despite this, we are excited by the potential of this work and look forward to seeing further results.”

 

Dr Mark Dallas, Lecturer in Cellular and Molecular Neuroscience, University of Reading, said:

“The authors set out to make designer molecules with the aim of preventing the aggregation of toxic proteins, in this case amyloid beta. While it provides a clear methodological approach and presents some evidence that these molecules can prevent toxicity in worms, we are a long way off establishing if this technology will be fruitful in our fight against Alzheimer’s disease. Furthermore, recent Alzheimer’s disease clinical trial failures using antibodies have suggested that targeting one specific peptide may not be enough to counter the devastating effects of dementia on the human brain.”

 

Dr David Reynolds, Chief Scientific Officer, Alzheimer’s Research UK, said:
“Antibodies that target amyloid in the brain are a promising approach for tackling Alzheimer’s disease. Using innovative computer design methods, the Cambridge team has shown that they are able to generate small antibodies to block key stages of amyloid build-up but these findings are at a very early stage. While this is an important first step, there is a long road between studies involving worms and cells and knowing if an experimental approach can provide benefit to people with dementia. Only more research will tell whether this type of antibody represents a new advance that could bring welcome advantages over what has already been tried.

“There are currently no treatments that are able to stop or slow the progression of Alzheimer’s or protect the brain from the damage of the disease. With over 500,000 people in the UK living with Alzheimer’s, and that number set to rise, it is vital that we continue to invest in research so that promising new findings like these can be translated towards medications that will change lives.”

 

* ‘Selective targeting of primary and secondary nucleation pathways in Aβ42 aggregation using a rational antibody scanning method’ by Aprile et al.  published in Science Advances on Wednesday 21 June.

 

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/tag/alzheimers/

 

Declared interests

Dr James Pickett: The Alzheimer’s Society funds a senior fellowship for the lead author (Francesco Aprile).

Dr Mark Dallas: No conflicts of interest.

Dr David Reynolds: No conflicts of interest.

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