Ready to divide and conquer

C&I Issue 17, 2009

Stem cells have been making a lot of headlines in the past few months. However, stem-cell based therapies really aren’t all that new, according to Brendon Noble, a stem cell expert at the University of Edinburgh’s new MRC Centre for Regenerative Medicine (CRM). As a former drug discovery scientist, Noble recalls: ‘I didn’t call myself a stem cell biologist or anything but we were working on compounds that make bones mend and 70% of the time what we were doing was tapping into stem cells that were already in all of us and can make more bone form. So we’ve been doing this for a long time in the body.’

Today, Noble’s research at Edinburgh involves a different strategy: this time, taking stem cells outside of the body and growing them on scaffolds before putting them back into animal models. Ultimately, the goal is to use the cells to repair cartilage and so help to prevent and even cure osteoarthritis, which is the fourth biggest reason for disability in the EU, Noble points out. ‘Cartilage is the body’s shock absorber to stop us hurting every time we move,’ he explains; unlike bone, it can’t repair itself after injury.

By curing diseases that would otherwise often be treated with traditional small molecule drugs, stem cell therapies threaten ultimately to wipe out swathes of existing pharma revenue streams. However, they also promise a new technology platform that could help to offset losses from patent expiries and dwindling drug pipelines. According to Insight Pharma, stem cell therapies are currently in development for Alzheimer’s disease (26.6m potential patients worldwide), cancer (20m new patients/year), cardiovascular disease (38m), diabetes mellitus (177m), Parkinson’s disease (6m) and spinal cord injury (2m). It cites Robin R. Young’s ‘oft-quoted projection’ of an $8.5bn stem cell market by 2016.

‘The[ir] precise contribution remains to be seen, but it is clear that stem cells will provide major benefits,’ says Ian Wilmut, who heads up the Edinburgh CRM: ‘In some cases, cells will replace those in the patient which have died or stopped functioning appropriately. In other diseases, stem cells will be used to deliver biologically active molecules to a specific location either to kill tumours or to provide support for tissue that is damaged.’

The world’s first approved stem cell therapy, meanwhile, could be on the marketplace as early as next year. Osiris Therapeutics’ Prochymal has already been fast-tracked by the US Food & Drug Administration (FDA) for use in the treatment of graft versus host disease – when the body rejects foreign tissues during bone marrow transplantation or after blood transfusion. Osiris plans to complete submission for a Biologic License Application (BLA), and says it will request a priority review for marketing approval by the end of 2009.

Prochymal will be the first stem cell drug to have gone through classical clinical trial pathway, including pivotal studies,’ says chief scientific officer Michelle Le Roux Williams. Like bone marrow transplants, which have been successfully used in the clinic since the 1960s, Prochymal uses adult stem cells derived from bone marrow. However, ‘Prochymal is very different from a bone marrow transplant,’ Le Roux says, as it comprises ‘a different class of [mesenchymal] stem cells… that give rise to tissues like bone and connective tissues.’ The hematopoetic stem cells involved in bone marrow transplants, by contrast, form red and while blood cells and platelets, designed to rescue the patients own blood forming system after chemo or radiation therapy.

In addition, the Osiris cells are grown and cultured in a GMP manufacturing process, Le Roux Williams continues, quite different from the way that cells are harvested for bone marrow transplants. As many as 10, 000 doses of Prochymal can be produced from a single bone marrow donation.

However, stem cell therapies are not just about using cells, but also about using molecules that direct those cells to behave as researchers would like, says Pfizer chief scientific officer Ruth McKernan. 'Stem cell therapy is all about controlling cell fate,' McKernan explains. In nature, cells carry around with them a complex but precise combination of growth factors, peptides and other molecules, carefully honed through many generations of evolution.

‘We can think of the cell as a drug delivery device for a combination of growth factors, peptide molecules that the body has optimised,’ McKernan says. ‘What happens in normal development is stem cells make a variety of cell types, but in the lab we can control cell fate by using traditional small molecules.’

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