Are stem cells the holy grail for medical research?
Donna Chisholm reports on the scientific advances that might help in the battle against disease.
If Dr Frankenstein were trying to create the fiend this century, he wouldn’t bother robbing graves – he’d surely try stem cells.
“This is science fiction come to life – it’s incredible,” said one doctor of the potential role of the cells.
Stem cells, found all over the body but more commonly in the blood and bone marrow, can grow into other sorts of cells. Through stem cells, science may one day be able to grow a body’s spare parts.
Already, international research has achieved stunning results. In Germany, heart attack patients grew new heart muscle from stem cells after doctors inserted purified bone marrow into their coronary arteries.
In Japan, scientists are using stem cells to create natural breast implants.
In the United States, paralysed actor Christopher Reeve is a passionate advocate of their potential in spinal cord injury.
New Zealand had its own stem-cell epiphany last year when Auckland University anatomy professor Richard Faull and his team serendipitously discovered stem cells in Huntington’s disease patients were making new brain cells in an attempt to repair damage.
The post-mortem discovery was the first time such activity had been detected in a diseased human brain. The finding has determined his team’s work for the next decade, says Faull.
“Suddenly it’s changed our whole perception,” he says. “We were all told the brain you got when you were fully mature was the brain you had for life and cells that die are never replaced. Now we know that’s absolute garbage and we have the capacity to make new brain cells throughout life and we try to repair disease by making increasing numbers of brain cells.”
While at present it’s too little too late, the important thing, says Faull, is that the machinery is there for the brain to repair itself and this natural process can, perhaps, be enhanced or stimulated.
“If we can find out what it is that turns on a stem cell and encourages it to make a particular type of cell in the brain or any part of the body that’s degenerating, that would be great.”
Just how important stem cells may be he doesn’t know. “All we see is the process when it fails – what we don’t know are the success stories; how many people there are out there who would have had brain disease if the process hadn’t worked.”
With dementia occurring in 8-10% of over-60s, a renaissance in neurodegenerative research has followed the realisation that Alzheimer’s isn’t just a by-product of ageing, but a disease. Faull says he won’t raise unrealistic hopes of a cure any time soon – “we always know when you get over one mountain you see the Himalayas before you” – but he predicts major advances in the understanding of the disease. Much of the work focuses on how to inhibit or genetically switch off beta amyloid, the toxic compound that accumulates in the cells and kills them.
“Because it causes a loss of the mind, if we solve this disease, we’ll know what makes up the human mind.”
And that means it will be a long way in the future.
To get a grasp of the complexity of brain research, listen to one of Faull’s colleagues, researcher Louise Nicholson: “When we talk about nerve cells, we are talking about something the size of the baseball with its arms that receive information occupying the relative size of a school hall. It’s sending out its own long lead with its own message from the hall all the way to Tiritiri Matangi island.
“It’s something we are really battling with.”
Do people understand the complexity? “I think we don’t understand it.”
She believes the next decade will see great improvement in the treatment of symptoms of other neurodegenerative diseases – for example, Parkinson’s – which will vastly improve quality of life.
Faull is also enthused about the impact attitude and Environment can have on the progress of brain disease. Animal studies have shown stem cells proliferate faster in a physically and mentally stimulating environment.
“`Use it or lose it’ is the key. People doing crosswords and chess, being more intellectually active is critical. Attitude and environment (are) very important in our ability to fight disease and we never thought this.
“Five years ago I would have said from my scientific pedestal that this is total rubbish. But we’ve just published a paper showing that putting animals with Huntington’s genes in an enriched stimulating environment slows the rate of loss of chemical receptors – it makes a major change.”
A key advantage for Faull’s group is his brain bank, which contains about 300 brains and comprehensive clinical histories of the patients who donated them.
The brain tissue is in big demand from researchers internationally.
The involvement of the brain may also be pivotal to a new arm of treatment to prevent
and treat diabetes, the disease tipped to become the country’s biggest health burden.
Auckland professor of biochemistry and diabetes researcher Garth Cooper says food processing has disorganised some of the “satiety signals” which tell the brain when you’re full.
Already, drugs giving the body a wake-up call that it should be becoming sated are in the late phases of clinical trials overseas and may be available in North America, Australia and Western Europe within a year.
The body isn’t good at sensing fat, relying usually on protein cues, says Cooper. For example, we can eat large amounts of chips – virtually protein-free – without the body sensing the lashings of saturated fat.
In the 1980s, Cooper isolated the hormone amylin, which improves the control of blood sugar levels in diabetics: high blood glucose levels damage the small and middle-sized arteries and this in turn affects blood supply to key organs, including the eyes, kidneys and nerves.
Cooper’s research thrust covers both type 1 diabetes, in which patients die if they are not injected with insulin, and type 2, in which about half of sufferers need insulin supplements but who continue to produce a significant amount.
History shows there is little likelihood of a major breakthrough in diabetes control, Cooper says, but the next 10 years should see drugs with new modes of action as well as a better understanding of how food and diet impacts on the disease.
“At a molecular level, we essentially do not know why the (insulin-producing) islets fail, we do not know what the fundamental mechanism underlying insulin resistance is or have a decent understanding of the molecular underpinnings of the complications.
“We should be very, very humble in acknowledging our virtual complete ignorance about all three aspects of type 2 disease.”
Combating so-called Coca-cola-isation – our “obesogenic environment” – will be a vital part of the diabetes fight, says Cooper. He foresees food manufacturers and the government collaborating to modify food composition.
Another key area will be drugs that could alter the way muscle disposes of fats. Widespread trials are under way overseas.
But diet, lifestyle and drugs will all need to play a part.
“It is an imperative we get this right because the progress of disease indicates that otherwise we will be facing even more serious problems than we are now. It is one of the major challenges of the next couple of decades.”
If diabetes is the coming challenge, the reduction of heart disease risk has been the success story of the past 20 years.
Incidence and death rates are dropping – but prevalence is still increasing, thanks to greater numbers of survivors and an ageing population.
It will be vital to target prevention and develop new factors to find out whether an individual is at risk, says Auckland cardiologist Harvey White.
Markers in the blood will determine whether the plaque in your coronary arteries is more likely to rupture, forming a clot which causes a heart attack. Catheters could, in future, target particular plaques and dissolve or reduce them.
But even now, says White, more patients could be saved if they were on the right combination of drugs.
He says everyone who has a heart attack or angina should take a combination of four heart treatments – aspirin, beta blockers, lipid-lowering statins and Ace inhibitors – but only about 20% do. Taken individually, each drug reduces risk about 20%. The combination reduces it 75%
As in cancer, the “next big thing” is what is known as proteomics – identifying patients most likely to benefit from, or suffer adverse reactions to, a therapy.
“For a drug like aspirin, there’s a 20% reduction in stroke and heart attack overall, but that 20% equates to 80% reduction in some patients and zero in others,” White explains. So only a small group of patients get the benefit of what amounts to a lot of treatment.
The maligned hormone replacement therapy may also have a future role for the heart – in about 20% of patients it increases the good cholesterol in the blood which scavenges the bad and reduces the risk of cardiovascular disease.
Other advances in sight do not involve drugs.
As the number of heart-disease survivors increases, there are likely to be greater rates of heart failure. For this, and for rhythm disturbances, mechanical devices may help.
Pacemakers are routinely used for correcting slow rhythms or sudden stops, but devices to help those whose hearts race and stop are likely to become much cheaper and more widely used.
In the meantime, says White, the government would ultimately save more money on health in the long term if it spent more now.
“I think we’re slipping and there is a real risk of disastrously slipping. Doing more interventions is cost effective and keeps patients from coming back into hospital. It gets them back in the workforce, or doing things we value – like a grandparent bouncing a grandchild on his knee or reading stories.
“The richer society gets, the more it appreciates that a good investment is health.”