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Stem Cells to Aid Search for New Drugs in Hard-to-Treat Conditions

Published: Monday, December 10, 2012
Last Updated: Monday, December 10, 2012
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StemBANCC consortium aims to derive 1,500 stem cell lines from 500 patients across eight diseases.

Stem cells are to be used in a £45m effort to look at providing new treatments for a host of complex conditions affecting large numbers of people, including Alzheimer's, Parkinson's, autism and diabetes.

However, it’s not the stem cells themselves that would form the new treatments. Instead, the stem cells would provide a platform to transform the process of discovering new drugs.

A Europe-wide consortium of over 20 universities and 10 pharmaceutical companies, led by Oxford University and Roche, is to generate a giant resource of stem cells derived from patients' skin or blood cells.

The StemBANCC consortium aims to derive 1,500 stem cell lines from 500 patients across eight diseases, using the techniques developed by Japanese scientist Shinya Yamanaka that saw him win a share of this year’s Nobel Prize for Physiology or Medicine.

'This has been shown for two or three patients for several indications; the proof of concept is there,' says Martin Graf, StemBANCC coordinator and head of Roche's Stem Cell Platform in Basel, Switzerland, explaining the scale of the project. 'We now plan to create 1,500 iPS cell lines from 500 patients.'

The researchers will then be able to use the 'induced pluripotent' stem cells, or iPS cells, to generate different tissue types - nerve cells, heart muscle, blood vessels, liver or pancreas cells, etc - against which drug compounds can be screened.

Testing drug candidates from the start in cells derived from patients - and so are directly relevant to the disease - will be much more relevant for coming up with effective treatments, the researchers say.

This approach to drug discovery could be particularly important in the diseases the researchers are interested in, where it has proved so difficult to come up with new treatments and where the pharmaceutical industry's most promising new drug candidates have often failed in late-stage trials.

'It’s the perfect platform for finding drugs. It's superior because we are looking directly at human cells from the patient, capturing the genetic complexity of the disease,' says Dr Zameel Cader, a consultant neurologist at the University of Oxford and principal scientist of StemBANCC.

Currently, many drugs fail late on in development because the tests used in the initial stages simply do not reflect what happens when the drug is administered in patients.

It is largely standard to screen compounds in lab cell lines that are often amenable to study but are nothing like cells in patients. Promising compounds then go into studies in animals before small-scale safety trials in humans look at safety.

It is only in larger trials, and after many millions of pounds have been spent, that it becomes apparent that the drugs have little or no effect in patients.

'The drug discovery process is flawed and isn't working. It needs reshaping, and stem cells may help provide this,' says Dr Cader.

StemBANCC would provide a good supply of cells directly from patients that 'recapitulate' the disease in the lab, and against which compounds can be tested from the start, the researchers say.

Heart, kidney and liver cells would also allow toxicological screens to help spot potential side effects early.

Dr Cader explains: 'The generation of the [stem cell] bank is the easy part, relatively speaking. The harder part is to show we can identify abnormalities [in the cell lines] relevant to disease.

'We believe we will be able to see abnormalities that are there in the disease. It will be hard. But if we find them, it will be superb. We can then apply [drug] compounds into our assays [lab-based tests] and see if these compounds correct the cellular abnormalities.'

The consortium will generate iPS cells from groups of patients with the following conditions: Alzheimer's, Parkinson's, autism, schizophrenia, bipolar disorder, migraine, chronic pain and diabetes.

The intention is to make the cell lines generally available to researchers help to improve the discovery of new drugs for these hard-to-treat conditions.

'Because the stem cells can be expanded indefinitely, we can essentially produce an infinite number of these patient-derived cells to work with,' explains Dr Sally Cowley of Oxford University. 'They can be stored, shipped around the world, and potentially made accessible to any researcher anywhere.'

Dr Cowley, who runs the stem cell facility at the Oxford Stem Cell Institute, part of the Oxford Martin School, adds: 'People may be working with these cell lines for decades, if we do it right.'

The €55.6 million funding over five years is made up of €26 million from the European Union's Innovative Medicines Initiative and €21 million in 'in kind' contributions from the participating drug firms in the European pharmaceutical industry association EFPIA. Contributions from other sources make up the rest.

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