Ten years of painstaking research has opened to door to safe new stem-cell treatments for a range of degenerative diseases
In November 2015 scientists at Edinburgh’s MRC Centre for Regenerative Medicine published research that finally addressed a question critical to the application of innovative cell therapies: is the genetic make-up of laboratory-grown stem cells stable, and therefore safe for use in clinical treatments?
Led by Dr Tilo Kunath, a University of Edinburgh Chancellor’s Fellow, the paper in Scientific Reports was the largest study ever conducted of therapeutically useful stem cells, and it paved the way for clinical trials of stem-cell treatments for conditions such as Parkinson’s disease, macular degeneration and spinal cord injury.
The team’s work brought to fruition a decade’s worth of effort into the production of human stem-cell lines and has opened the door to novel stem-cell treatments. These therapies, which harness stem cells’ ability to grow into any type of specialised cell, offer the prospect of regenerating cells that are lost, damaged or dying as a result of disease or injury.
Dr Kunath’s lab specialises in Parkinson’s disease research, and develops stem cells that can turn into dopamine-producing neurons. Dopamine is a neurotransmitter that sends messages to parts of the brain that control movement. In people with Parkinson’s disease, the nerve cells that produce dopamine die. The hope of regenerative medicine is to replace these dopamine-producing cells with stem cell-derived nerves transplanted directly into the brain.
“For many people with Parkinson’s disease, this will be transformative,” says Dr Kunath. “It will rebuild their dopamine network, reverse their symptoms and allow them to live without Parkinson’s medication. They will effectively be disease-free.”
One of the primary concerns about generating stem cells in a laboratory setting has been that as the cells multiply, they can accumulate genetic abnormalities. These mutations may affect how the cells behave once transplanted into humans and could, for example, cause cancer or other disease.
One means of minimising this risk is to ensure that stem cells have been developed in precisely the right circumstances, having had no contact with animal products or other contaminants, and been fully traced from their original tissue sample. These are termed ‘clinical-grade’ stem cells, and are deemed fit for use in human patients.
Dr Kunath’s latest research has investigated a large collection of clinical-grade stem-cell lines, and found most cell lines possessed large genomic variants that reflected the natural genetic diversity found in the human population. By using a technique called molecular karyotyping, a highly sensitive method of detecting genetic abnormalities, Dr Kunath and his colleagues established the unique genetic signature of each cell line and found that they did not develop mutations that could pose a risk to human health.
“This work is painstaking and methodical, and we now have a greater appreciation of the genetic diversity of stem-cell lines,” says Dr Kunath. “We have now developed a publicly available resource for scientists around the world, so that they can track and trace any of these cell lines and trust that they can be used safely.”
We have now developed a publicly available resource for scientists around the world, so that they can track and trace any of these cell lines and trust that they can be used safely.
The project was funded jointly by the Medical Research Council and the Cure Parkinson’s Trust. Tom Isaacs, founder of the Cure Parkinson’s Trust, who has lived with the disease for 22 years, feels passionately that this development is crucial to the future of Parkinson’s treatment.
“Everything we fund has to make an impact on the disease within five years,” explains Mr Isaacs. “Tilo’s work defines which avenues we should go down in the pursuit of stem-cell treatments, and that has value for the whole arena of Parkinson’s research.
“What people with Parkinson’s disease want is a renaissance, a rebirth, and stem cells offer that opportunity,” continues Mr Isaacs. “For us, this research is not simply about the realisation of a therapy, it is also about the hope of that realisation. The hope is what will change attitudes to Parkinson’s disease, it will change the outlook for people who receive the diagnosis, and ultimately it will change the quality of life for people who live with the disease.”
Dr Kunath’s research has unsurprisingly attracted great interest from people who live with Parkinson’s disease, and he is closely involved with the local Research Interest Group run by Parkinson’s UK. Its chair, Professor Ken Bowler, who is also Emeritus Professor of Physics at the University, sees great value in promoting scientific research to those living with the condition.
“There has been a great deal of hype around stem-cell research, so it is important that we can access and promote genuine science,” Professor Bowler comments. “We know that there is definitely a real prospect of this work succeeding. It is not a miracle cure, and we know it will not work for everyone. But these treatments are now a reality. It is wonderful to see this work unfold and to witness scientists working at the cutting edge of scientific possibility.”
With clinical trials anticipated across Europe before 2020, and efforts to broaden access to stem-cell therapies already in motion, Dr Kunath feels certain that the landscape of Parkinson’s treatment is set to change.
“It is a hugely exciting time as we have tackled practically all of the scientific challenges,” he says. “Now it is just a case of refining the logistics and practicalities of delivery. I feel very passionately that this will change care for many people with Parkinson’s disease. It is incredible to be able to tell neurologists that they are going to see some of their patients get better. I am absolutely convinced this will change lives.”
Photo © Tricia Malley Ross Gillespie www.broaddaylightltd.co.uk