Pioneering treatment in which replacement gene placed in cold virus 'container' to be tested on 250 patients
Gene therapy may offer new hope for those with heart failure struggling to live a normal life if the first British trials in humans, announced on Tuesday, are successful.
The two trials, involving about 250 patients, will look at whether the pioneering treatment is safe, reduces emergency admissions and improves quality and length of life.
Over a decade ago gene therapy, in which working copies of missing or faulty genes are inserted into the human body, was widely viewed as a panacea, but until now it has failed to deliver on its early promise. Scientists hope the two heart failure trials will be a turning point for the technique, as well as benefitting people with a devastating condition.
There are more than three-quarters of a million people in the UK with heart failure who are breathless, exhausted, and become increasingly debilitated as their heart, often damaged after a heart attack and sometimes following cancer treatment, labours with increasing difficulty to pump blood around their body. Drugs do not work well, and eventually the only hope is a heart transplant.
"In the most severe group, this is as bad as the worst cancer, with 30% mortality in the first year," said Dr Alexander Lyon of Imperial College London and the Royal Brompton Hospital, who is lead investigator in the UK for both new studies.
The trials are based on 20 years of research in the lab and recent safety trials in patients in the US. So far, 37 people in the world have had gene therapy for heart failure, but until now, the experiments have aimed only to investigate its safety.
One of the trials involves patients at the Royal Brompton in London and the Golden Jubilee hospital in Glasgow, which are among 25 centres in Europe and 25 in the US. In total there will be 200 patients, half of whom will get gene therapy and the other half a placebo. That trial is funded by Celladon, the US biotech company which is providing the treatment for both.
The other trial, at Harefield and Papworth hospitals, will give the gene therapy to patients who already depend on a machine known as a lower ventricular assist device (LVAD) to pump the blood around their body after heart failure.
That trial is funded by the British Heart Foundation, which has also supported 20 years of research. The treatment aims to increase the expression in heart muscle of a protein produced by the SERCA gene, which signals a flow of calcium to the muscle cells, which then contract. More calcium means a stronger heartbeat.
One of the problems scientists have encountered in previous gene therapy trials has been delivering the gene to the place where it is needed – the right cells in the right tissue – and preventing it from causing problems when it get there.
The first big breakthrough for gene therapy was in the treatment of boys born with a rare disease of the immune system called x-SCID. But this proved to be a false dawn when two of the first patients were diagnosed with leukaemia caused by the gene therapy treatment in 2002.
In the new treatment, the SERCA gene is smuggled into the cell in a specially modified common cold virus, which consists only of its outer shell housing the one critical strand of DNA. The treatment is infused into the carotid artery through a line passed up from the groin.
Although the gene will end up delivered by the virus to cells throughout the body, it has an effect only in the heart muscle, because the protein works on a structure within the cell called the sarcoplasmic reticulum, which is not found in non-muscle cells.
"It's been a painstaking, 20-year process to find the right gene and make a treatment that works, but we're thrilled to be working with cardiologists to set up human trials that could help people living with heart failure," said Professor Sian Harding, professor of cardiac pharmacology at Imperial College, who developed the treatment. "It's been a long journey to get to this point and we are proud to have helped to develop the first therapy under investigation in clinical trials for people with heart disease."
Professor Peter Weissberg, medical director of the British Heart Foundation, said the treatment was "a great example of bench to bedside medicine".
"There was a terrific fanfare around gene therapy 10 to 15 years ago – it was going to cure everything. It was not that simple. This team has done all the painstaking research. It is a great example of the slow burn of getting laboratory science translated into clinical medicine," said Weissberg.
He said the treatment was "highly promising". It could be eight years or more before the therapy is generally available, if all goes well.
The potential gains are great. The treatment itself costs hundreds or possibly a few thousand pounds (depending on dose), but is a one-off, although scientists are working on the possibility of developing a top-up.
However, the cost of an LVAD mechanical pump is £30,000-£40,000 before it even comes out of the box, while a heart transplant costs £200,000 and every hospital admission sets the NHS back about £3,000 per patient. Reported by guardian.co.uk 2 hours ago.
Gene therapy may offer new hope for those with heart failure struggling to live a normal life if the first British trials in humans, announced on Tuesday, are successful.
The two trials, involving about 250 patients, will look at whether the pioneering treatment is safe, reduces emergency admissions and improves quality and length of life.
Over a decade ago gene therapy, in which working copies of missing or faulty genes are inserted into the human body, was widely viewed as a panacea, but until now it has failed to deliver on its early promise. Scientists hope the two heart failure trials will be a turning point for the technique, as well as benefitting people with a devastating condition.
There are more than three-quarters of a million people in the UK with heart failure who are breathless, exhausted, and become increasingly debilitated as their heart, often damaged after a heart attack and sometimes following cancer treatment, labours with increasing difficulty to pump blood around their body. Drugs do not work well, and eventually the only hope is a heart transplant.
"In the most severe group, this is as bad as the worst cancer, with 30% mortality in the first year," said Dr Alexander Lyon of Imperial College London and the Royal Brompton Hospital, who is lead investigator in the UK for both new studies.
The trials are based on 20 years of research in the lab and recent safety trials in patients in the US. So far, 37 people in the world have had gene therapy for heart failure, but until now, the experiments have aimed only to investigate its safety.
One of the trials involves patients at the Royal Brompton in London and the Golden Jubilee hospital in Glasgow, which are among 25 centres in Europe and 25 in the US. In total there will be 200 patients, half of whom will get gene therapy and the other half a placebo. That trial is funded by Celladon, the US biotech company which is providing the treatment for both.
The other trial, at Harefield and Papworth hospitals, will give the gene therapy to patients who already depend on a machine known as a lower ventricular assist device (LVAD) to pump the blood around their body after heart failure.
That trial is funded by the British Heart Foundation, which has also supported 20 years of research. The treatment aims to increase the expression in heart muscle of a protein produced by the SERCA gene, which signals a flow of calcium to the muscle cells, which then contract. More calcium means a stronger heartbeat.
One of the problems scientists have encountered in previous gene therapy trials has been delivering the gene to the place where it is needed – the right cells in the right tissue – and preventing it from causing problems when it get there.
The first big breakthrough for gene therapy was in the treatment of boys born with a rare disease of the immune system called x-SCID. But this proved to be a false dawn when two of the first patients were diagnosed with leukaemia caused by the gene therapy treatment in 2002.
In the new treatment, the SERCA gene is smuggled into the cell in a specially modified common cold virus, which consists only of its outer shell housing the one critical strand of DNA. The treatment is infused into the carotid artery through a line passed up from the groin.
Although the gene will end up delivered by the virus to cells throughout the body, it has an effect only in the heart muscle, because the protein works on a structure within the cell called the sarcoplasmic reticulum, which is not found in non-muscle cells.
"It's been a painstaking, 20-year process to find the right gene and make a treatment that works, but we're thrilled to be working with cardiologists to set up human trials that could help people living with heart failure," said Professor Sian Harding, professor of cardiac pharmacology at Imperial College, who developed the treatment. "It's been a long journey to get to this point and we are proud to have helped to develop the first therapy under investigation in clinical trials for people with heart disease."
Professor Peter Weissberg, medical director of the British Heart Foundation, said the treatment was "a great example of bench to bedside medicine".
"There was a terrific fanfare around gene therapy 10 to 15 years ago – it was going to cure everything. It was not that simple. This team has done all the painstaking research. It is a great example of the slow burn of getting laboratory science translated into clinical medicine," said Weissberg.
He said the treatment was "highly promising". It could be eight years or more before the therapy is generally available, if all goes well.
The potential gains are great. The treatment itself costs hundreds or possibly a few thousand pounds (depending on dose), but is a one-off, although scientists are working on the possibility of developing a top-up.
However, the cost of an LVAD mechanical pump is £30,000-£40,000 before it even comes out of the box, while a heart transplant costs £200,000 and every hospital admission sets the NHS back about £3,000 per patient. Reported by guardian.co.uk 2 hours ago.