Dealing with dementia

Hungarian and Israeli scientists have taken an important step forward in the quest to cure dementia.

The world’s largest pharmaceutical companies are trying to find a cure for Alzheimer’s Disease and other forms of dementia, which now affect 5-8 percent of those aged 60 and over, estimates the World Health Organisation. Yet it may well be a small Hungarian firm and its consortium partners that have edged them closer to the big breakthrough, thanks to EUREKA project SAMBA.

The project leader TargetEx has just 14 full-time workers but managed to complete an ambitious project to identify and test molecules that could target the enzymes believed to cause Alzheimer’s in the brain: BACE-1 and Acetylcholinesterase. “These results were really promising because two of the small molecules developed caused activity in mice”, said György Dorman, TargetEx’s head of medicinal chemistry. Those molecules can now be further explored.

TargetEx’s important findings were carried out faster than much research because the company worked with Israeli scientists at Pepticom, which used computational technology involving some of the most sophisticated computer modelling and algorithms in the world to design combinations of peptides (compounds of amino acids) that could simultaneously target BACE-1 and Acetylcholinesterase.

They also partnered with Amiram Goldblum’s team at the Hebrew University of Jerusalem, which invented an algorithm to help solve problems associated with drug design and discovery – the winner of the 2000 American Chemical Society prize. Professor Goldblum’s group contributed to the identification of potential small molecules acting on both targeted enzymes. « We knew how efficient Professor Goldblum’s bioinformatics tools were,” said TargetEx’s chief executive Sándor Cseh.

The fourth consortium partner, Hungarian National Institute of Tuberculosis and Pulmonology tested the best compounds developed on a type of transgenic mice that are good models for the symptoms of dementia.

‘These results were really promising because two of the small molecules developed caused activity in the mice’ – György Dorman, head of medicinal chemistry at TargetEx

Growing markets

The Israeli expertise allowed TargetEx, which carried out the laboratory work, to cut initial research time and costs considerably and to go on to test 100 peptides identified as potentially suitable for targeting the enzymes.

The team stresses that the results are preliminary and more research is needed on the two structures that caused changes in the mice since they weren’t able to show reductions in the beta-amyloid plaques that are produced in the brain of Alzheimer’s patients. However, the discovery is enough to prompt TargetEx, representing the research partners, to seek a U.S. patent. TargetEx, which works as an outsourcer to pharmaceutical companies, biotech companies and research institutes, also believes some combinations of proteins developed can be sold to clients to be used in other drugs.

Companies are increasingly buying in innovation to supplement their own drug discovery efforts – an outsourcing market that is worth billions and continues to grow. Samba has also given TargetEx a first foothold into the important life science market.

All the partners in the consortium are now well placed to serve the market for pharmaceuticals for Alzheimer’s, which is set to grow to an estimated 4.5 million euros in 2022, compared to 3.0 billion in 2016, estimates consultant Zion Market Research.

Peptide has already benefited, with turnover up 50 percent on its first year 2012 after the SAMBA project finished in 2015 and allowing it to operate with 50 percent more staff.

The success gives an important boost to European research since the region is coming under increasing competition in the biotechnology sector from countries like China and India where patent applications are growing fast.

“What made the relationship so good was that our partners all had unique skills that would have been very difficult to find elsewhere,” said Cseh.

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