I've seen a couple of stories in the press about the death of Lorenzo Odone, who had adrenoleukodystrophy (ALD). ALD occurs when an essential protein that removes very long chain fatty acids (VLCFAs) is missing, resulting in a build-up of VLCFAs in the body which damage the brain. Most sufferers die within 1 to 10 years of showing symptoms.
Lorenzo Odone lived until the age of 30, despite doctors giving him little chance of surving beyond the age of 8 or so. His relative longevity has been ascribed to 'Lorenzo's Oil', a mixture of glycerol trioleate and glycerol trierucate. The oil was initially used as a treatment by Lorenzo Odone's parents, who were understandably unwilling to simply watch their son die. They undertook a considerable amount of research, despite being laypeople with no medical expertise. They thought that the oil would help inhibit the creation of VLCFAs. Lorenzo's condition apparently stabilised after the oil became part of his diet. Since two laypeople creating a therapy that had eluded the finest minds of medicine is quite a story, a film was made, titled 'Lorenzo's Oil'. The money the Odone's made from the film went into the Myelin project, which funds research into diseases like ALD and MS.
However, the Odones found the scientific community sceptical. In the Guardian obituary, Lorenzo's sister Cristina Odone writes "Not all members of the scientific community welcomed this approach; or, indeed, their portrayal on film as hard-hearted and arrogant. A backlash against the Odones saw various researchers from around the world denying the efficacy of Lorenzo's oil, and most doctors refused to prescribe it. In 2005, however, the world's top authority on ALD, the late Dr Hugo Moser, published the findings of a 10-year study which showed that a statistically lower incidence of ALD occurred in those boys whose diet included Lorenzo's oil". This is what interested me in the story, as it fits into a neat narrative about laypeople taking on the might of the scientific establishment, and being treated in a cold-hearted and callous manner as a result.
Firstly, I would say that an initial sceptical approach was sensible. The only evidence that Lorenzo's Oil might work was from the apparent stabilisation in the condition of Lorenzo himself. There could be a huge number of other reasons why this happened that had nothing to do with Lorenzo's Oil. The only way to find out whether it really worked or not was to conduct scientific trials. Until this had been done, it was sensible to be sceptical of a therapy for which there was essentially no evidence of efficacy.
So, what of Moser's study? This is certainly not my area of expertise, but I can at least have a look at the methodology of the paper. The trial followed 89 boys who were thought to be at risk of ALD based on an assay of VLCFAs in their plasma. All of the boys were given Lorenzo's Oil and 'moderate fat restriction' in their diet. The study concluded that treatment with Lorenzo's Oil caused a reduction in plasma hexacosanoic acid, which was associated with a reduced risk of developing abnormalities on an MRI scan. However, this was a single arm trial: there was no placebo group. I'm not criticising the study for this; if the treatment is likely to help, then it is probably unethical to withhold it from the subjects of the study. But it does make it more difficult to know whether the results are because of the therapy, or because of something else. What would be more interesting, I think, would be to look at whether there is a difference between subjects given Lorenzo's Oil and a reduced VLCFA diet, and those just given the diet. As far as I can tell, this has not been done. So it is difficult to know if the oil has any effect on its own. A more recent study in the journal Metabolic Brain Disease followed 11 subjects, all of whom were taking Lorenzo's Oil and were on a diet restricted in VLCFAs. Again, this doesn't allow us to separate the effects of the oil from the effects of the diet.
While these studies might show some evidence for an effect of Lorenzo's Oil before symptoms appear, it seems that the treatment doesn't work well in symptomatic subjects. This may be because the compounds that make up Lorenzo's Oil do not cross the blood/brain barrier.
Now, I'm not saying that Lorenzo's Oil doesn't work. This isn't homeopathy, after all, and there does seem to be a plausible mechanism by which it might work. I'm not even saying that what the Odones have acheived is not impressive. What I am saying is that the evidence that it does work is fairly weak, it is far from being a miracle cure, and the story is a little bit more complicated than the narrative that is being presented.
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7 comments:
I never knew that Cristina Odone was related to Lorenzo of 'Lorenzo's Oil'. Actually, I think the only thing I did know about Cristina was that she once had trouble editing her own entry on Wikipedia and had to send a copy of her passport to a Wikipedia Editor.
Yes, I didn't know that either. The only thing I remember about Cristina is related to an early post here, where she irritated me by claiming that the Catholic church has some sort of monopoly on "charity, compassion, self-sacrifice and modesty".
And I spelled her name wrong.
Yes. I only realised Cristina Odone was related to those Odones when she wrote something in her Observer column that told the story in a way that cast the “blinkered scientists” rather overtly as the bad guys. I wrote the Observer an annoyed letter at the time (which they didn't print) because as written it was (i) wrong and (ii) meat and drink to sundry Alt Loons. You will note they had to print a somewhat shamefaced correction about the doctors she was dissing.
The Odone parents’ achievement with the oil was definitely a considerable one, but the film was fairly clearly “Hollywood-ed Up” to highlight the “against all odds and the vehement opposition of hidebound experts” narrative. Having said that, though, Cristina Odone is pretty sane about medicine, science and scientists, certainly by the standards of national newspaper columnists. For instance, you can see her defending the reputation of the late Sir Richard Doll here (where critics on the thread include tiresome perennial blog-troll uber-idiot John Stone of JABS, aka “Pluralist”), and talking about MMR here.
dr aust
Thanks for those links. It is, as you say, 'meat and drink to sundry Alt loons'.
Interesting also to see that Cristina Odone has a relatively sane attitude towards science. Especially as she seems so totally bonkers on the Catholic advocacy front.
It's also interesting that in the piece about Lorenzo's Oil that dr aust linked to, Cristina Odone is apparently advocating the use of a medicine, the patent of which is held by her father. I'm emphatically not accusing Cristina of anything dodgy here. There is, after all, some evidence that the oil might do something. But can you imagine the uproar if the column had been about, say, vaccination?
Yes, interesting to wonder what the spin would have been, Paul.
BTW, the Lorenzo's Oil paper makes clear (in the end under "Conflict of Interests") that Augusto Odone has signed all the product royalties he gets over to the Myelin Project, which is a charitable foundation he and others set up to fund research into demyelinating diseases and to help sufferers and their families. So he doesn't make any money out of it personally.
I think the point of the study design is that the prognosis is so bad for the "at risk" kids (judged as being that way by the fact that the plasma C24 lipid assay shows their levels are already high) that their only real therapeutic option is bone marrow (i.e. stem cell) transplant. But finding donors for that would likely be a problem, so the longer the boys can be kept "asymptomatic" the better. Odone co-authored the paper (and some others) with the world authority on the disease and its treatment (the late Hugo Moser), so it is a model of how you should do it, really. You could contrast it with some of the appalling quack therapies being peddled for autism.
There is an interesting obit for Hugo Moser, who was fictionalised as the Peter Ustinov character in the Lorenzo's Oil film, and who died just last year, in the Guardian here. The obit is part-written by Augusto Odone, who talks quite touchingly about his and Moser's real-life relationship and how it was portrayed in the film.
dr aust:
Yes, I should have made clear that the royalties were going to the Myelin Project, so thanks for pointing that out. As I said, I wasn't accusing Cristina Odone of anything dodgy, but if you were an alt med loon that's exactly the sort of apparent conflict of interest you would jump on in order to discredit Odone's piece.
I should also say that I wasn't criticising the research. It's clearly a situation in which the ideal of a double-blind, randomised, placebo-controlled trial is going to be impossible to realise. The point was only that given the current state of the evidence, it isn't really clear how much Lorenzo's Oil helps as compared to the reduced fat diet. While the oil certainly seems to be useful, it isn't the miracle cure you might imagine it is from reading the press.
As always, thanks for the comments and links: I always learn something from them.
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