Sauron
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RIP Lorenzo Odone, 1978-2008
The young man named above ought to be an icon of amatuer science.
Lorenzo was the son of two World Bank economists, an Italian and his American wife. At age 6 he was diagnosed with a rare and little understood
disease called ALD. ALD is a genetically transmitted disease passed from mother to son. Daughters can only be carriers, never victims. The disease
results in the demyelination of nerve fibers. The doctols told the Odones that their son would not live past 8.
Well, he dies yesterday at age 30.
The story of why was dramatized in the Nick Nolte-Susan Sarandon film LORENZO's OIL. I recommend it. To summarize, the Odones, with no training in
chemistry, biochemistry, pharmacology or medicine set out to educate themselves in these disciplines, organized and funded international conferences
on ALD and almost alone, did what medical science had been too distracted to accomplish: come up with a succesful, simple therapy for ALD boys.
ALD works by allowing fatty acids to accumulate in the blood stream and dissolve myelin. By rationalizing the mechanism of this process for the first
time, the Odones were able to conceive of a competitive inhibitor, erucic acid, principle component of rapeseed oil. Against medical advice they
obtained pure erucic triglyceride ester and fed it to their son. Soon his blood fatty acid levels began to drop.
The therapy could not remyelinate Lorenzo's nervous system. But no further deterioration took place. And ALD boys newly diagnosed and with little
neurological damage, when started on the therapy also showed no signs of the normally remourseless progression of the symptomology of ALD.
(AdrenoLeukoDystrophy, by the way.)
Augusto Odone obtained a patent on the therapy and founded The Myelin Foundation.
His wife died in 2000 and now with Lorenzo gone, Augusto Odone plans to sell his house in Fairfax Virginia and return to Italy.
Shining examples of what motivated amateirs can achieve.
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12AX7
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Was his cause of death related to the ALD?
Heartwarming story.
Tim
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not_important
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http://news.bbc.co.uk/2/hi/health/3907559.stm
He died of pneumonia after getting food stuck in his lungs.
http://www.news.com.au/heraldsun/story/0,21985,23787743-663,...
that sort of thing is not uncommon with people having nerve damage or musculature problems that prevent ready movement and body control. So not
directly from the disorder, but likely as a result of the condition.
a bit more at Wiki (gasp!)
http://en.wikipedia.org/wiki/Augusto_and_Michaela_Odone
http://en.wikipedia.org/wiki/Adrenoleukodystrophy
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blogfast25
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Interesting and moving story. I'd never heard of Lorenzo Odone before...
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Sauron
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Heartwarming?
The Odones helped a great many other people's sons but, tragically, their own and only son was too far gone to do much good. They prolonged his life
to be sure. But from about age 6-7 he could not see, speak, hear, smell, walk. He was a prisoner inside his own mind.
Susan Sarandon received an Academy Award for her portrayal of Lorenzo's mother. See the movie. It is well worth your while.
Heartrending, I'd say.
[Edited on 31-5-2008 by Sauron]
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12AX7
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Quote: | Originally posted by Sauron
But from about age 6-7 he could not see, speak, hear, smell, walk. He was a prisoner inside his own mind. |
Ah, that would pretty well suck then...
Quote: | Heartrending, I'd say.
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Ah, better word for it.
Tim
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beastmaster
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A moving and inspirational example of what we as humans can do if we are motivated. My prayers to the family.
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brew
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Kind of puts things in perspective when a situation like that described is presented. It also is motivating as I am working towards a degree in
Biomed, and if I work hard and think creatively, I too may be able to contribute. Thankyou for posting this story
bmc
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Sauron
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Adrenoleukodystrophy, IIRC, affects one boy out of 10,000 and prior to the Odone oil therapy, those boys were condemned to death before age 8. Now
most of them can live normal lives not because of CDC Atlanta or Mass General or Johns Hopkins or some other center of medical research, and certainly
not because of any of Big Pharma who wouldn't go anywhere near such an "orphan" disease. But because two amateurs cared enough to apply themselves in
a race against death - a race they won.
Sadly we cannot expect all orphan diseases to be so tractible of a therapy, but that should not prevent us from trying.
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FreedomFighter
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That's the boy from the film "Lorenzo's Oil".... R.I.P.
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Jdurg
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Please don't think that Big Pharma won't research a disease because they don't care. It costs BILLIONS of dollars to research a medication and have
it meet all of the legal and regulatory requirements of safety agencies across the globe. If the risk of financial ruin for failing to come up with a
successful compound didn't exist, there would be a lot more research into the more "obscure" diseases and conditions out there.
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Sauron
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Big Pharma does not research diseases like ALD which involve too few sufferers to be potentially profitable. Hence "orphan diseases".
In the case of ALD, when the Odones announced their success with use of triglyceride of erucid acid, which was bootlegged in from the UK, the parents
of ALD boys facing imminent death screamed for rapid FDA approval and got it.
When HIV sufferes clamored for fast track approval of AZT they got it, too.
AZT was not developed to treat HIV, at all. So in this instance Burroughs Wellcome got a free ride and rapid approval because of the political clout
of the gay community. They didn't spend billions developing AZT for an anti-HIV treatment, and they didn't spend billions getting FDA approval - did
they? No more than the Odones spent billions developing rapeseed oil and olive oil, or getting FDA approval.
But of course, you are right, that the way the system is set up at present, Big Pharma MUST spend billions of dollars on R&D and then dealing with
the Feud & Drag Administration (as my old boss, who consulted for FDA, called them.)
(No doubt Burroughs Wellcome did spend a lot of money developing AZT for whatever its original application was, but they got to sell it for that,too,
after it was fast tracked for AIDS. So the money did not go to waste, far from it.
[Edited on 1-6-2008 by Sauron]
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Nicodem
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Since I happen to do work for the so called "Big Pharma" from time to time, I do know that Sauron is absolutely correct in his claims that they are
not interested in developing cures for orphan diseases, antibiotics or any other medicines that are used either by only very, very few affected (like
ALD patients) or very seldom and for too short periods of time (like antibiotics and similar medicines). The reasons are like always connected with
money. Statistically common chronic diseases that still don't have effective enough cures are the main target of the Big Pharma. Alternatively, new
chronic syndromes and pathologies are being proposed in order to launch new drugs on the market (this is especially common practice for
psychopharmaceuticals). It is however interesting that nowadays with the occurrence of bugs resistant to common antibiotics, some attention is
nevertheless being paid again to this field (after many decades of doing nothing!). However the registration expenses are a real obstacle so unless
this problem becomes more urgent only the academic sphere will do research (and we all know that academic research in the pharmaceutical area is only
to get papers published and not to develop drugs). Yet, the orphan diseases generally are of just about no interest to anybody but those affected and
their families. So the example of the Odone family is indeed something outstanding.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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Sauron
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Apropos your remark about newly coined syndromes justifying investigational psychopharm agents, I note that there was or is some controversy about
Palatine's application for approval of PT-141 aka bremelanotide, for treatment of female sexual dysfunction.
The controversy is about whether FSD exists or not.
In a more general light, FDA insists that drugs cannot be approved for anything other than treatment of disease. Aging is not a disease per se so FDA
effectively blocks research into the extension of the human lifespan. Medications have to be directed toward a particular aspect of aging:
arteriosclerosis, senility, coronary dieases, are all fair game. This strikes me as an odd impediment to some potentially very valuables lines of
research, and I have a hard time working out the rationale for this policy.
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Tacho
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The history of the Odones always impressed me a lot. I have folowed their lifes since I watched "Lorenzo's oil". It is really a movie that makes me
think about what we can acomplish. What they did was amazing. I cannot stop wondering that, if Augusto and his wife had the internet we have today,
their son's (and all ALD victims') history could have been very different.
As for the "Big Pharma", its Darwin's natural selection. Companies that cannot pay their bills cease to exist. Governments and non-profit institutions
moved by donations are the only ones that can (or should) spend money on research of rare diseases. And governments would be wasting taxpayer's
money, because many, many people die of common diseases that could be cured with just a little extra investment.
[Edited on 2-6-2008 by Tacho]
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Sauron
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The fact that pharm companies are profit driven is plain, but that does not make it an endearing trait.
Even in the public sector, the research budgetary process is far from being a zero-sum game. Every dollar spent on X is a dollar not spent on Y.
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Tacho
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True, but the "mean-corporations-are-the-source-of-all-evil" approach does not help to solve the problem.
I was very touched by the Odone story. I fell sorry for Lorezo and wish all the best to Augusto, but I'm aware that those feelings exist because their
story was on a well made movie and, of course, the parents' achievement was remarkable.
As you point out, reason, not emotion or media, should decide whether the money goes to X or Y.
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Sauron
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I'm far from anti-corporate. I do think that Big Pharma is having a bit of an image problem and could take steps to improve their PR.
Also note that the pharm companies do upgefuck, at great cost. They spend those billions on R&D of a drug that then does not make it through the
costly regulatory approval process. After all that is what the regulators are there fore. If we could trust the pharm companies to self regulate we
would not need the FDA. Bitter experience tells us otherwise.
Look at that truly horrendous debacle with an investigational drug in Europe a year or two ago. A German pharm company was paying a British contractor
to run human clinical trials on paid volunteers and these went horribly wrong. That was the end of the program for this drug. (No one died but about a
dozen people, a large segment of the test group, had terrible, life threatening reactions.)
You would have expected that the developers would have had some clue as to the possibility of such, but no, nothing had shown up in in vitro tests or
animal studies.
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Jdurg
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The drug discovery/production process is pretty interesting. First, a chemist has to come up with a compound based upon research. (E.G. they don't
go and mix random things together and hope to find something. They look at the condition they are trying to find a treatment for and first work out
if they can create something through a computer). So initially, a lot of chemical research takes place on computers. If they create something, they
then have to go and ensure that there are no patents out there for that compound as you don't want to get sued for selling something that you claimed
you created when in reality some other company did it.
Then, once the compound is made and fully documented on how to make it, it will go through a massive database of compounds to search for any similar
structures that have toxic side effects. If the structure of it matches up with a known "toxic" compound in the database, the drug is terminated. A
large number of drugs tend to die here. If it isn't matched up with a toxic compound, it will go to animal trials. If it doesn't pass those trials,
it is terminated.
If it does pass animal trials, it still needs approval for First In Human trials. Then it still has a long way to go before it's approved and allowed
for general release. Typically, if it's a compound that helps a widespread problem the FDA and other regulatory agencies will give it an "expidited
approval process".
Sadly, all the computer simulations and animal trials in the world can not fully reproduce reactions in humans and contraindications with other
compounds. If it could, my job would be a HELL of a lot easier.
It's really sad that we can't create compounds for a low cost with no safety concerns for every condition out there. It's just that all the money
required to keep up those databases, pay all the people who work on the research and development, pay for the advertising and pay for the
application/registration fees, etc. etc. has to be made up somehow. Typically, exclusivity and patent protection is so short for new drugs that if
you don't meet your expected sales of the compound you'll lose money on it. It sucks.
You can never truly understand how much money, time and effort it takes to create a drug until you've seen the process.
That is why I praise the Odone's for what they've done. They were able to do research without having to go through the FDA or the regulatory
agencies. As an independant group, they didn't have to deal with the fears of being sued and losing billions upon billions of dollars. Since their
goal was to just treat the disease and no worry about payroll, marketing, application fees, etc. the research for them was much easier than it would
be for an organized corporation.
Oh yeah, the history of the FDA is also very interesting. They initially weren't developed to "protect" the public, per se. They were developed due
to people selling things that had no active component in it, but claiming that it did. So the FDA was developed as a way to stop scammers and let the
public know that something they approved actually had what it said it did in it.
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Sauron
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Well, for openers, it helps to have some knowledge of the biochemistry of the disease or syndrome so that there is some basis from which to
rationalize a therapy.
Pharmacologists have a lot of data about the effects and side effects of existing therapeutic agents and so that gets factored in.
There are a number of pharmacological and physiological paramaters that the compounds needs to posess, most of which are unfamiliar to chemists
outside of medicinal chemistry, for example log-p which is the octanol-water partition coeffecieint, which speaks to bioavailability.
So the pharm company might say to the chemists, "Find us compounds that have this range of molecular weight, this range of log-p, and contain the
following substructures."
Previously this might have rapidly proceeded to a broad synthetic attack, but nowdays the battleground is silicon. QSAR is relied upon increasingly to
predict the physical, chemical, and pharmacological properties of compounds not yet synthesized. This is in response to the high cost of synthesis as
well as advances in computing power and speed.
Once QSAR (Quantitative Structure-Activity Relationships) applications have screened candidates, then combinational libraries can be put to work to
rapidly and efficiently prepare and screen candidates for particular activity - often without isolation and purification. The main tools here are
those of parallle synthesis.
]
If everything goes well, then a relatively few candidates will emerge which can be isoloated, purified, characterized, and subjected to further tests
for the particular properties desired, along with requisite low toxicity.
At this point methodology reverts to the more conventional.
Note that a lot of important discoveries are still made by serendipity.
Substances being screened as potential therapies for one thing turn out to have powerful therapetic effects in a totally unected direction.
This has happened over and over again and is of course the obverse of promising drugs which turn out to have negative side effects.
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phlogiston
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I met Augusto Odone in person at a scientific meeting a few years ago. Theirs is an beautiful story of love-driven determination, and I wish them all
the best. I have been working on this disease and the transporter that is deficient in these patients (ALDP, a peroxisomal membrane protein of the
ABC-transporter family) for several years now. Believe me, a real effort is being made by many scientist to cure these patients (and many others
suffering from all kinds of rare metabolic disorders)
Note, BTW, in contrast to what was suggested in the movie, Lorenzo's oil does not actually cure or halt the progress of the disease, not even if you
start early. Trials in patients have shown this. It does dramatically reduce the plasma levels of very-long-chain fatty acids, but it does not affect
the progress of the disease. The severity of ALD patients is highly variable: some patients live to grow pretty old with very few symptoms, while
others suffer from a rapidly progressing childhood form of the disease. The reason for this is unknown, but I think it is possible that Lorenzo would
have lived equally long as he did even if he was not given this oil.
Current strategies being tried are gene therapy or drugs that upregulate alternative metabolic pathways.
-----
"If a rocket goes up, who cares where it comes down, that's not my concern said Wernher von Braun" - Tom Lehrer
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methyl_ethyl
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As you all have stated quite eloquently, "Big Pharma" has no interest in developing drugs for orphan diseases (developing being the operative word
here), however small biotech has funded more than a few long term R&D programs on licensing / milestone / royalty payments paid by big pharma for
development of orphan drugs. Granted only the creme de la creme are seen, acknowledged, and licensed by big pharma, however this has become the
business model for many small biotech companies.
At the heel of the hunt no big pharma has any real vested interest in developing orphan drugs, however if a small company has the resources to take a
drug through phase I/II and is fortunate enough to yield some really decent data; big pharma is much more inclined to take a closer look. Quite often
if the small company is run well, this can work to their advantage and they can make out with enough capital to fund R&D for another few years.
If the company is not run well however, the company is susceptible to the vices of big pharma, and may be eaten alive, used, abused, sued, and
tattooed.
Just wanted to point out that Big Pharma does in fact care about orphan diseases, they just don't want to put capital up front to fund the development
of it if the outcome is not guaranteed through at least Phase I/II. And that may be the only reason small Biotech companies are still around...
much_love
methyl_ethyl
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Sauron
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The pharm companies have boards of firectors answerable to stockholders and the stockholders want to see ROI (return on investment).
It's just the way the world goes round.
Sic gorgeamus a los subjectatus nunc.
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