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A much loved six-year-old boy mysteriously begins to lose his sight,
stumble into walls and lose his balance. Doctors diagnose a rare and fatal
genetic disease of the nervous system, giving the boy just two years to
live. The parents, neither of whom is scientifically trained, vow to find
a cure. Against all the odds, and often in the face of a sceptical medical
establishment, they come up with a treatment, an oil that snatches their
son from death and offers hope to thousands of other sufferers worldwide.

If this sounds like the plot of a Hollywood movie, that’s because it
is. But the movie in question, Lorenzo’s Oil, is far from medical fiction.
It is based on the real-life experiences of Michaela and Augusto Odone,
whose son Lorenzo was diagnosed as having adrenoleukodystrophy (ALD) in
1984. Since the film’s release in the US last December, the story of the
Odones’ heroic quest for a cure has won the hearts and minds of film critics
and public alike. But now, as the film is being released in Britain, a bitter
twist has emerged: Lorenzo’s oil has no effect on the course of ALD, according
to clinical trials conducted in the US and Europe, the results of which
are explained in the latest issue of the Journal of NIH Research. The treatment
everyone wants to believe in doesn’t work, say ALD researchers, many of
whom now condemn the film for raising false hopes.

ALD is a degenerative disease that only affects boys and has symptoms
similar to those of multiple sclerosis. As it takes hold, the insulating
sheath of myelin that surrounds nerve fibres is gradually stripped away,
causing a breakdown of the nervous system, paralysis and eventual death.
Most patients live for only two years after diagnosis, but Lorenzo is still
alive at 14, albeit almost completely paralysed. His parents attribute his
long survival to a dietary supplement based on two fatty acids, erucic and
oleic acids – the oil of the film’s title. ‘In our opinion the disease has
been halted,’ says Augusto Odone. ‘He is doing things he couldn’t do before.’
And Hollywood reinforces this view with zeal. By the film’s close, the oil
has not only halted Lorenzo’s deterioration but protected numerous other
children around the world from the ravages of ALD.

It is this portrayal of Lorenzo’s oil as a certain protection against
the disease that is now under attack. Hugo Moser, a neurologist who has
spent the past three years conducting clinical trials of Lorenzo’s oil at
the Kennedy Krieger Institute in Baltimore, has tested it on 257 patients.
Calling the film ‘an abomination’ which ‘overstates the benefit of the oil’,
he puts Lorenzo’s long survival down to natural variability in the severity
of the disease. Even without the oil, a dozen other patients with ALD have
lived until their teens or early 20s, he says.

Moser has more reason than most to be bitter about the film. In it he
is portrayed – under a different name, by Peter Ustinov – as a character
who obstructs and impedes Augusto Odone’s path to the successful cure. Yet
other researchers, with no obvious axe to grind, are equally convinced that
Lorenzo’s oil is a false dawn. William Rizzo, a neurologist at the Medical
College of Virginia, who worked with the Odones in developing the oil, not
only agrees with Moser’s interpretation of the clinical results, but believes
the film is positively harmful: ‘The movie implies Lorenzo’s oil is a cure,
and that if parents don’t get satisfaction from doctors they can go out
on their own and come up with cures for diseases. It’s not that easy.’

Parent power

The impact of the film and the Odones’ apparently unshakable faith in
Lorenzo’s oil is already being felt in clinics. Paediatric neurologists
say they are pressured by parents to provide a treatment they know will
not halt the disease. John Stephenson of Glasgow’s Royal Hospital for Sick
Children, who is becoming increasingly reluctant to prescribe the oil, says
that to use it now would be ‘treating the parents’ rather than the child.
The oil has an unpleasant taste – Stephenson likens it to engine oil –
and in some patients hinders blood clotting: about half of those who take
it become prone to slow-healing cuts and bruises.

Attempts to assess the oil’s efficacy have been hindered because the
mechanism of ALD is still a mystery. The disease is caused by a genetic
defect on the X sex chromosome: like haemophilia, it shows up in boys but
is carried by girls (who inherit a defective X gene from their mothers).
For the 1 in 25 000 boys born with the defect, the prognosis is bleak.
About half will develop ALD in childhood, while the remainder invariably
develop a milder form of the disease, adrenomyeloneuropathy (AMN), which
strikes between the ages of 25 and 40. Its progress is less rapid, but in
the end no less destructive.

Researchers have yet to discover why some boys with the defective gene
suffer ALD, while others develop AMN. Nor do they know why the genetic defect
causes the destruction of myelin sheaths. What is well established, though,
is that blood samples from boys carrying the genetic defect have unusually
high levels of saturated ‘very long chain’ fatty acids (VLCFAs), especially
hexacosanoic and lignoceric acids. Some VLCFAs are synthesised inside the
body from shorter fatty acids; others are present in food. But whatever
their origin, it seems that in healthy people these substances are rapidly
broken down. This has inspired the notion that VLCFAs cause demyelination
if allowed to accumulate in the blood, though the connection between fatty
acids and the ALD gene remains obscure.

In 1984, when the film takes up the story, the only way doctors could
respond to ALD was by excluding saturated VLCFAs from the patient’s diet.
But this approach, developed by Moser, fails to slow the progress of the
disease because the body produces its own VLCFAs.

The Odones, refusing to believe a cure could not be found, read everything
they could about ALD and the biochemistry of fatty acids. Saturated and
unsaturated VLCFAs differ only in the chemical nature of certain links in
their molecular chains. Yet whereas saturated VLCFAs are implicated in the
destruction of myelin, the unsaturated ones are presumed innocent. Then,
says Augusto, came ‘the Eureka moment’: he realised that the enzyme that
converts small saturated fatty acids into saturated VLCFAs in the body also
acts on unsaturated fatty acids.

To him, the corollary was obvious: it might be possible to prevent patients
from making saturated VLCFAs by feeding them unsaturated VLCFAs. These,
he reasoned, might act as molecular decoys, ‘distracting’ the enzyme responsible
for converting short-chain saturated fatty acids into VLCFAs. Odone decided
that to test his theory he needed a preparation based on two acids – oleic
and erucic. The problem was to find a suitable supply of edible erucic acid.

Eventually he persuaded a British firm, Croda Universal of Hull, and
a retired chemist, Don Suddaby, to take up the challenge. In 1987, Suddaby
delivered the edible form of refined erucic acid to the Odones. Soon afterwards
the Odones tried a mixture of dietary oils, first on Lorenzo’s aunt, who
carries the ALD gene, and then on Lorenzo himself. In both patients, the
levels of saturated VLCFAs in the blood dropped to normal levels. Yet though
remarkable, this did not signal a cure. Then, as now, there is no proof
that the build-up of VLCFAs in the bloodstream causes ALD; it could just
as easily be an effect of the disease. Yet although it was still clinically
untested, Lorenzo’s oil was quickly approved by the US Food and Drug Administration
as an experimental dietary supplement which doctors could give ALD sufferers.

Thus far the story is uncontentious. What angers researchers such as
Moser is the widespread belief that the oil is a cure. His findings to date
show that while the oil does indeed reduce the level of saturated VLCFAs
in the blood – just as Odone’s theory says it should – it has no discernible
effect on the progress of the disease. Once demyelination has begun, says
Moser, reducing levels of saturated VLCFAs to normal is useless.

Moser divides his 257 patients into three groups. The first of these
consists of 96 boys suffering, like Lorenzo, from ALD. ‘My experience is
that the oil does not change the course of that illness,’ says Moser. Last
autumn Moser and his colleagues published a paper in the Journal of Inherited
Metabolic Disease showing that boys who received the oil after their nervous
systems had begun to degenerate lived on average only 20 months after diagnosis
– no more than boys who died from ALD in the past, before the oil was disovered.

The results from the second group, 100 adult men suffering from AMN,
are more equivocal. In these patients, says Moser, the oil appears to improve
the ability of nerve fibres to conduct electrical impulses – one of the
key functions destroyed by demyelination. But Moser is cautious about this
finding’s significance: overall, he calls the result ‘a marginal improvement
in an otherwise wholly negative study’.

A crucial, but as yet unanswered, question is whether the oil can prevent
the onset of ALD. The 61 boys in Moser’s third group had no symptoms when
doctors first gave them the oil. According to Moser, 53 of these boys are
still free of symptoms, but only time will tell whether any of them escape
ALD because of the oil. In the meantime, the news is hardly reassuring.
One boy in the group has developed ALD despite his treatment starting when
he was three, and his blood levels of saturated VLCFAs having always been
normal. Body scans indicate that a further seven boys have begun to develop
the early signs of demyelination. ‘It is not 100 per cent preventive,’ says
Moser. ‘The jury is still out.’ Croda, which manufactures and holds the
patent on Lorenzo’s oil, declined to comment to ¿ìè¶ÌÊÓƵ on the results
emerging from the clinical trials. Last month, however, the company told
the Stock Exchange that it plans to expand its interests in ‘therapeutic’
oils: its share price rose about 5 per cent in a day.

Meanwhile, Moser’s pessimism is echoed by other researchers, some of
whom were initially optimistic about Lorenzo’s oil. It was Rizzo’s team
in Virginia that confirmed that the levels of VLCFAs in Lorenzo’s blood
had come down to normal after treatment with the oil. ‘I got very excited,’
says Rizzo, ‘and we started to treat other patients.’ Having conducted his
own trials on 18 boys with ALD, he is more downbeat. ‘I thoroughly agree
with his (Moser’s) data,’ says Rizzo. ‘You do a lot of things you think
logically will help. But many times they don’t work.’ Like most ALD researchers,
Rizzo credits Odone for his tenacity and insight, but is also adamant that
the film goes too far in its claims.

Nobody doubts that giving an obscure genetic disease Hollywood status
will help to raise funds for research. But as Rizzo puts it: ‘There are
families out there that think the oil is a cure, and it isn’t. And there
are alternative approaches that should be tried and might be missed.’

Julian Coleman is a freelance science writer.