Genetics - key to our future health

David Labanyi asks the experts to diagnose the future for health

David Labanyi asks the experts to diagnose the future for health

When leading clinical researchers in the State were asked what advances in treatment and therapies the next five to 10 years would bring, there was consensus on two points.

Firstly, significant advances in treatments for conditions like cancer and rheumatoid arthritis are on the way. And secondly, researchers also agree many drug therapies will become increasingly personalised as more details of a patient's genetic make-up are revealed.

Dr Ruth Barrington, chief executive of the Health Research Board (HRB), said people should examine treatments taken for granted today, when looking at what developments to expect over the next 10 years.

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"I heard the word 'stent' for the first time about five years ago. Now it is the device of choice for so many problems with the heart," Dr Barrington said.

The HRB also invests in the infrastructure required for research. More than €12 million will be spent on cancer research trials over the next three years and funding has been secured for a national imaging facility at St James's Hospital, Dublin. Dr Barrington uses the development of imaging technology as an example of the pace of medical research. "A few years ago, not many people were talking about imaging being important. Now, it is probably the most exciting technology for health research available."

Clinical research activity in Ireland is on the increase. Last year, 334 projects were submitted to the HRB for consideration. In 2004, it was 300, and in 2003, the total was 240.

"The quality is improving too. We know this because every application is peer reviewed. People are very impressed by the research ideas," said Dr Barrington.

Only 25 per cent of the projects submitted can expect funding. Dr Barrington anticipates marked advances in personalised medicine in the next 10 years.

"So many drugs are prescribed because a trial showed that in enough patients it had an effect. But an average is a very blunt tool. Researchers are very excited about the idea that drug treatments can be adapted based on a patient's genotype."

In 2005, the HRB committed €53.5 million to research projects, the majority of which - €44.6 million - was in bio-medical sciences. An example of this type of research is being carried out by Prof Tim O'Brien, a consultant endocrinologist at University College Hospital Galway and director of the Science Foundation Ireland-funded regenerative medicine institute, Remedi, at that university.

Prof O'Brien is interested in genetics as a therapy, rather than as a diagnostic or prognostic tool, and concentrates on heart failure, osteo-arthritis, spinal cord injury; diseases for which there is no effective treatment.

"We are hoping to get away from the paradigm of people requiring transplantation or hip replacement by aiding their regenerative capacities."

This requires the bringing together of gene therapy technology, biomaterial science and adult stem cells. "In gene therapy applications, one delivers genes to diseased tissues. The main challenge is getting the genes to the site of the disease."

The plan is to deliver genes to stem cells and then inject them into diseased patients, where the stem cell will carry the gene to the desired site, he said.

"Heart failure is quite common and its prevalence will increase as the population ages. So we would like to allow cardiac regeneration in patients with this condition. The same principal will apply to the joints and other injured tissues," said Prof O'Brien.

"We are working with medical device companies to develop systems where these therapeutic products can be delivered to the body in a minimally invasive manner," he said.

Trying to better understand why people get sick is the focus of the research carried out by Luke O'Neill, professor of immunology at Trinity College Dublin.

"My research is trying to understand the nuts and bolts of the immune system. You need a robust immune response to pathogens, like pneumonia or Hepatitis C or Aids."

Prof O'Neill said several drugs were in development to more effectively treat rheumatoid arthritis, multiple sclerosis and Crohn's disease and with less side effects.

He expects the bio-pharmaceutical sector to show the most significant developments over the next decade as clinicians use computers to assess DNA sequences.

This area, known as bio-informatics, concentrates on the genetic variations between patients.

"Some patients respond differently to a drug because their genetic background is slightly different.

"We are trying to use that kind of genetic information for more personalised medicine."

Drug companies are also using this technology to make decisions about which drugs to send to trial. "Pharmaceutical companies are looking for ways to decide more quickly which drugs have potential," he said.

Prof John Crown, a consultant oncologist, concedes there is unlikely to be a Eureka moment over the next decade when a cure for cancer is found.

However, he said there would be constant progress in treatments for the disease. He is particularly excited by the "molecular therapeutics", a sector where he anticipates revolution.

Prof Crown uses the analogy of the smartbomb and the blunderbuss to describe the technique. "We can now focus on what's wrong with the cancer cell rather than a blunderbuss treatment designed to kill all rapidly growing cells."

An example of this is a new drug therapy for chronic myeloid leukaemia (CML). "The single biggest improvement has come in the area of , following the introduction of a drug called glivec. This is a specific molecular agent, and it has revolutionised the treatment of that disease."

Another drug for which Prof Crown has high hopes is herceptin, which early trials show reduces the risk of a secondary breast cancer by 50 per cent.

The drug works by concentrating on one gene and Prof Crown, who jointly led the Irish part of the international study into this drug, said its success offered a clue to the way forward for researchers.

"The approach we are going to see in the next 10 years in Ireland is giving patients combinations of molecularly-specific drugs.

"A lot of old-fashioned treatments will be phased out. Many newer treatments are tablets and relatively non-toxic and will be given in doctors' offices and outpatient clinics. Because the treatments are less toxic, fewer patients will be admitted to inpatient wards to deal with side effects, so they will relieve pressure on beds."

Blackrock Clinic founder and orthopaedic surgeon Jimmy Sheehan anticipates a drop in the volume of exploratory procedures as diagnostic techniques are improving so quickly. And he believes the crossover between engineering and medicine is driving many of the new clinical developments. "Things like stents are all based on technology," he said.

Dr Fergal O'Brien is an example of this crossover between engineering and medical research, with a background in mechanical engineering and a research focus on orthopaedic tissue engineering.

As the principal investigator in the Trinity Centre for bio-engineering, Dr O'Brien is working on a way of repairing broken bones using a minimally invasive technique that promotes the body's own natural regeneration.

"We get bone cells to grow in a collagen scaffold and rather than use a bone graft, you can inject this mineralised material to the damaged bone."

The scaffold is strong enough to allow weight bearing while the fracture is repaired. He foresees the technique being used instead of reconstructive surgery.

"When you see old ladies bent over, it is because the vertebrae have collapsed. The idea is you could introduce this reconstructive bone," he said.

Dr O'Brien hopes to go to clinical trials with the technology within the next five to 10 years.

The largest provider of State-funded research is Science Foundation Ireland with an annual budget of €140 million.