Focus: The billion-dollar fight for life

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The Independent Online
ALL HUMAN beings suffer from an incurable disease. It is called mortality. Although the condition is terminal there are increasing signs its early symptoms may be treatable. Ageing cannot be reversed but it may, perhaps, be delayed.

Since the disease is universal, the attraction is irresistible for pharmaceutical companies. Anti-ageing treatments that work would have a vast market, particularly in developed countries where the proportion of the population over 60 will increase markedly. No wonder that companies such as Glaxo Wellcome, Eli Lilly, Pfizer and SmithKline Beecham are pouring funds into the field.

Research on the disagreeable side-effects of ageing spans everything from diseases of the central nervous system, to diabetes, brittle bones and arthritis. It is a highly competitive field, and none of the main pharmaceuticals groups will indicate what proportion of their R&D spend goes on tackling the diseases of old age. Martin Sutton, spokesman for Glaxo Wellcome, said: "If a disease is becoming more prevalent because of an ageing population, we will naturally focus on that."

Across the industry, several hundred medical compounds that can boost memory and learning ability are being investigated. Research teams are examining genes for Alzheimer's disease and the mechanisms that cause cells to age and die. Surgical procedures involving the transplantation of embryonic cells into brains damaged by age and disease are also being developed. At the end of a century that has seen spectacular advances in longevity, ageing itself is taking over as the new target for therapeutic innovation. The aim is to add life to years, as well as years to life.

Any disease associated with ageing offers pharmaceutical companies a fast-growing market. Ninety per cent of diabetes, for instance, is the type II version that hits the over- 50s. SmithKline Beecham estimates patients worldwide will double to 110m by 2010 because of the ageing population. Analysts at SG Securities, the investment bank, expects the diabetes treatment market, now worth $6bn, to deliver 19 per cent annual growth to 2002. Dr Anthony Rebuck, vice- president and director of clinical R&D at SmithKline Beecham, said: "Type II diabetes is becoming increasingly recognised. Where people used to say, `Auntie has a touch of sugar', now it's recognised as diabetes."

Osteoporosis treatments provide another huge market, which Lehman Brothers' "Pharma Pipelines" estimates will grow from last year's $4.25bn to $11bn in 2002. In this case, most of the drugs are preventative. Eli Lilly is the market leader with its Evista drug, whose sales rose 63 per cent last year. A similar pattern can be seen in the market for inflammatory/rheumatoid ar-thritis treatments. SG Securities estimates the arthritis market is worth $6.5bn, and will grow by 14 per cent annually.

But it is a cure for dementia that remains the holy grail for anti-ageing researchers. The benefits of a longer life expectancy are clouded by the fear of degenerative diseases of the central nervous system (CNS). SG Securities estimates the total CNS market is worth $20bn with compound annual growth of 16 per cent to 2002. Alzheimer's treatments are probably worth no more than pounds 500m, says SG's Michael King, but should deliver 40 per cent growth annually. Novartis, Eisai, Eli Lilly, Pfizer and Smith- Kline Beecham are the leaders in CNS. "The market will be huge," says Mr King.

The race to find an effective treatment for Alzheimer's and other dementias, which affect one in 20 people over 65, rising to one in three over 85, has spawned speculation about "memory drugs." Some experts claim that, as well as helping granny recall what she had for breakfast, they will turn ordinary students into double first graduates. Research involving steroid drugs and growth hormone, among others, has shown improving normal memory is theoretically possible.

Steven Rose, professor of biology at the Open University, says there are ways to manipulate learning so a weak experience is laid down as a strong memory. "But there are chemicals which can enhance a memory, improving the chances of its being recalled. They will not restore your memory of an event 20 years ago but they may help you remember better at the end of the day what happened at the beginning. That would be a bonus for Alzheimer sufferers."

There are an estimated 800,000 people with memory loss in Britain and the number is expected to double in the next 20 years. If the onset of dementia could be postponed by five years the number of people affected would be halved.

The two drugs licensed in the UK - donepezil (brand name Aricept, marketed in the UK by Eisai and Pfizer) and rivastigmine (Exelon, made by Norvartis) - show some benefit in a small proportion of patients for a limited time but they have side-effects. Prescription volumes of Aricept in the US have risen from 50,000 at its launch in 1996 to almost 300,000.

Such drugs are recognised to be a first step in treatment for the disease but no more than that. Other compounds in the pipeline include metrifonate from Bayer and galanthamine from Shire Pharma- ceuticals. Galanthamine, a natural constituent of snowdrop and narcisssus bulbs, has been claimed to produce a "highly significant" improvement in reasoning ability without serious side effects.

None of these drugs is a cure, nor does any halt the progression of the disease though they may slow it. Also, the improvement is only temporary, giving a respite of perhaps six months or a year in the mental deterioration. Several genes are thought to be involved in the development of Alzheimer's disease, which is caused by increased production of a protein called beta-amyloid laid down in the brain, leaving a slowly growing trail of destruction. Others, such as the Apo E4 gene, are thought to be implicated in creating the tangles of fibres that are also a distinctive feature of the brains of those with Alzheimer's. This research is being done by Glaxo Wellcome, Eli Lilly, Pfizer and SmithKline Beecham, among others. Glaxo Wellcome appointed Professor Alan Roses, one of the world's leading authorities on dementia, from Duke University in the US, to run its Alzheimer research programme.

Another focus of attention for companies is Parkinson's disease, the neurological disorder that leaves sufferers with a tremor in the hands and difficulty walking. Lehman estimates the global market for Parkinson's treatments is $1bn, but that it will rise to $1.5bn by 2002. SB estimates 0.2 per cent of the total population suffers the disease, but these make up 6.8 per cent of the nursing home population. As the proportion of ageing population increases, so will the number of cases. There were 500,000 sufferers in the US last year.

But the biggest stumbling block to any effective drug treatment for Alzheimer's or Parkinson's is that by the time the symptoms are evident the patient's brain is already extensively damaged. Drugs cannot repair the brain, they can only make the best of what is left. So scientists have experimented with replacing damaged tissue or persuading damaged cells to regrow and reconnect. Adult brain cells cannot be transplanted and survive but animal experiments using foetal brain cells have been successful. The technique has been tried, with some success, in humans with Parkinson's disease.

Possibly the most exciting area of research, but also that furthest from yielding concrete results, is that into telomeres, which may hold a key to ageing. The Geron Corporation, founded by the Texan billionaire Miller Quarles, is pioneering research into telomeres, which are present in every cell. Telomeres shorten with every cell division, like a burning fuse, and when they can shorten no more, the cell dies.

Last year, Geron scientists found a way of inhibiting the enzyme, telomerase, to prevent the shortening of the telomeres and in effect extending the lifespan of the cell. But telomeres are only one determinant of ageing. Some cells, such as muscles and nerves, do not divide but nonetheless die off in time. Rat cells produce quantities of telomerase but their telomeres don't shorten - yet they still die in a couple of years.

Geron has recently taken over Roslin Biomed, the commercial arm of the Roslin Institute in Edinburgh where Dolly the sheep was cloned, to boost its expertise in this frontier area of research. Analysts warn that its breathtaking stockmarket rating is based on theoretical argument rather than concrete results. But although its work is still only a step from science fiction, it has sown seeds of hope.