Over 100 Italian and UK scientists and politicians came together on 12th December for a Summit on Regenerative Medicine organized by the Italian Embassy in London and the School of Science Technology and Health, University Campus Suffolk. Their aim: to bring the collective expertise of academics, industry and the political world to bear on the question of how to take basic stem cell research towards the clinic.
Taking research to the clinic is no simple task. Discussions at the Regenerative Medicine Summit covered a wide range of ideas and challenges faced by the field:
- Cell therapy: the fourth pillar of healthcare?
- Meeting a need - treating patients
- Making cells and searching for drugs
- Delivering cells to patients
- Setting standards
- Good science is the answer
Cell therapy: the fourth pillar of healthcare?
In a keynote address, Chris Mason of University College London visualized healthcare as a building, with cell therapies the fourth pillar needed to support the roof – our medical need. Today's healthcare has three pillars in place:
- Pharmaceuticals – chemically manufactured medicines such as aspirin
- Biologicals – a medical product such as a protein or antibody, made by a biological process
- Medical devices – for example, pacemakers, blood sugar meters
These three pillars are very successful and improve the lives of millions of patients, but we still have an 'overhanging roof' of unmet medical need. Now we're building a fourth pillar, cell therapy, to tackle currently incurable conditions like degenerative diseases or HIV. But the supporting foundation of the building, the infrastructure for manufacturing the therapies and delivering them to patients, is not there yet says Mason: “It’s no good inventing a light bulb if you don’t have wires or electricity to power it”.
Meeting a need
Patients around the world are placing their hopes in new therapies based on stem cells. Charles Sabine, NBC War Correspondent[EK1] , faces the prospect of Huntington’s disease in the coming years. His father has already died from the disease and his brother is severely affected. Knowing that has inherited Huntington’s and will have to tread the same path himself, Sabine spoke passionately to the experts at the Summit about their responsibility to work hard to fulfill the hopes of future generations of patients.
A cure for Huntington’s disease is likely to be some way in the future, though many researchers around the world are focusing their efforts on the disease and the cells it affects. In some other areas, research is a little closer to the clinic: For example, Pete Coffey of The London Project to Cure Blindness explained how 10 patients with age-related macular degeneration will have a layer of retinal cells made from embryonic stem cells inserted behind their eyes in a phase 1 clinical trial due to begin in the UK in early 2012. Such trials are exciting and will provide evidence about the safety of particular treatments, but the day’s discussions also highlighted a number of key challenges for the cell-based therapies of the future.
Making cells and searching for drugs
Many of the scientists at the Summit have worked with stem cells for years, and have developed meticulous procedures for using them to make a particular type of specialized cells, such as neurons (nerve cells). But no-one in the room on 12th December claimed this is easy to achieve. And scaling up a process that works in a small dish in the laboratory to produce huge vats of cells for large-scale medical use is going to be a big challenge.
Manal Hadenfeld of Life & Brain in Bonn, Germany, argued that close collaboration between academic researchers and industry is going to be vital. The Bonn company was created by the University of Bonn and operates on a site that brings together University and commercial researchers. They are developing techniques for differentiating stem cells, purifying the cells they want and ultimately creating automated procedures that could be used to manufacture cells. They see drug development as a major application of stem cell research. Once you can make lots of cells reliably, you can use those cells to test libraries of substances to identify possible drugs for treating diseases.
This is something Marc Peschanski of iSTEM is working on too, and he echoed Hadenfeld’s view that industry-acadaemia partnership is important. Peschanski is using embryonic stem cells with the genetic defect that causes Huntington’s disease to look for possible new drugs. He believes it makes sense to collaborate with industry on this kind of work, since pharmaceuticals companies have access to large libraries of substances that can be searched for drug candidates by testing them on cells that act as a model to represent a Huntington’s patient.
Delivering cells to patients
Taking new stem cell therapies to the clinic is not something biologists and pharmaceutical companies can do alone. Developing automated systems for making cells is an engineering task. And physicists have an important role to play as well: new imaging technologies are needed to watch where cells go when they are injected into the body, and what they do. The laboratory dish is quite a different environment from the body!
Even before research reaches clinical application, storage and distribution of cells will play a key role in opening up the road to therapies, argues Pasquale de Blasio of BioRep Milan, Italy. BioRep establishes cell lines, stores them and distributes them to laboratories for research. De Blasio believes coordinated networks of stem cell banks are needed to ensure a supply of cells that meet high standards – where the source, the method of growing the cells and detailed information about cell type is known.
And it’s already time to think ahead and consider how to deliver cells to patients, believes Simon Ellison of the UK’s National Health Service’s (NHS) blood and transplant service. He argues that the answers are already there, in the bone marrow transplant, organ transplant and blood supply systems. The NHS has been delivering stem cells to patients in the form of bone marrow transplants for decades. Existing experience already tells us how to get cells to patients, what works in hospital environments and what clinicians need – we don’t need to reinvent the wheel.
Standards were a recurring theme in discussions at the Summit: scientific, ethical and legal. How can procedures for making cells be standardised? And for testing or distributing them? How much do we need to know before we can take treatments to the patient? asked one delegate. Unproven therapies are being tried in unregulated countries, often with claims of great results. But the consensus was clear: giving patients untested treatments without proper consideration for safety or monitoring of results is just not acceptable. Clinical trails must be designed to maximize patient safety and to weigh potential benefits properly against risks.
Nevertheless, some felt that the regulations for clinical trials are too complex and burdensome. Academic researchers are getting involved in clinical trials and it is proving difficult without the well-established structures and resources of industry, and with new kinds of therapies. The challenges of making the right rules and regulations for cell therapies were highlighted by Christian Schneider of the European Medicines Agency, the regulatory body responsible for approving medicines for release in Europe. Cells are not like aspirin, he explained. Cells are much larger than a molecule like aspirin, they are very complex and they are hard to ‘standardise’ because they change and respond to their environment. But he emphasized that regulators are not trying to make rules that insist on ‘zero risk’ for new therapies – that’s not possible. Instead, they want to make sure risks are analysed and controlled. “Regulators should be both gate keepers and enablers of new medical technologies’, said Schneider.
MP George Freeman pointed out that politicians have a role to play in regulations and it is important that MPs are talking about the issues. He said the UK government is looking at how to help with the process of clinical translation, and he emphasized the importance of open discussion of the challenges. Ignazio Marino, President of the Italian Senate Committee on the National Health Service agreed that discussion with both politicians and the public is important. He pointed out that regulations about embryonic stem cell research differ between countries and argued that parliament should not translate religious or moral principles into law, but should be driven by benefits to society.
Good science is the answer
In the words of Elena Cattaneo, one of the Summit’s organizers and Director of the Centre for Stem Cell Research at the University of Milan:
“Science is a way for us to develop as human beings, and to help others. We are walking through a desert of the unknown and it would be immoral to exclude any possible direction for research that could cure terrible diseases like Huntington’s Disease. We must be guided by the evidence: science must be visible and repeatable, and it is vital that we all work together in this endeavour.”