The Doctor, The Father, The Movie and the Medicine: Lorenzo's Oil Update

[Guest guest]

To all ers,

I know this is not about CMT, but it is 'neurological' and involves

myelin and many of us are familiar with the story of Lorenzo's Oil.

So, if you don't want to read this update, just delete this message

now. Otherwise, read on. ~ Gretchen

The Doctor, The Father, The Movie and the Medicine

Cast apart by 'Lorenzo's Oil,'

Two unlikely collaborators Write their own sequel

By JONATHAN EIG

Staff Reporter of THE WALL STREET JOURNAL

October 8, 2005; Page A1

In the Hollywood version of the tale, Hugo Moser was the obstinate

scientist who stood in the way of a family trying to cure a boy's

rare and fatal disease. Augusto Odone was the heroic father who

fought to save his son.

But the story didn't end with the 1992 movie " Lorenzo's Oil. " Dr.

Moser is 80 years old now, Mr. Odone is 72. Thanks to a surprising

discovery and another tragedy, the oil that brought these two men

together and drove them apart prompted one more scene no one saw

coming: a reconciliation.

" If we made this story up, " Dr. Moser says, " no one would have

believed it. "

In the autumn of 1983, 5-year-old Lorenzo Odone (pronounced oh-DOH-

nay), began slurring his speech. His parents had recently moved to

Washington from Africa's Comoros islands, where Mr. Odone, an

Italian, worked for the World Bank. They told themselves that their

son's strange speech patterns had something to do with his new

environment. Then came the tantrums, the clumsy falls and the hearing

loss. They had no explanations for those.

The following spring, a neurologist told Lorenzo's parents their son

had adrenoleukodystrophy, or ALD, a hereditary disease that affects

about one in 21,000 males. The neurologist sent them to the man who

probably knew more about the disease than anyone else: Dr. Moser,

director of the neurogenetics research center at the Kennedy Krieger

Institute in Baltimore and a professor of neurology at s Hopkins

University.

The Odones couldn't understand why a perfectly healthy boy would

sicken so fast. They refused to accept the diagnosis, which offered

no hope for a cure. Dr. Moser gave them a piece of conclusive

evidence: A blood test on a Odone, Lorenzo's mother, showed

she was a carrier for ALD.

Though the news was devastating, Dr. Moser had a soothing effect. He

is a silver-haired man with ruddy cheeks. His patients gently tease

him for the sloppy way he eats. They also talk about his resemblance

to a well-worn teddy bear.

He spoke calmly and slowly to the Odones in a German accent. In

patients with ALD, he explained, the body fails to break down certain

types of fatty acids, which are produced by the body and found in

food. As these acids accumulate in the brain, neurological problems

begin. In boys, symptoms typically appear between the ages of 2 and

10. Nerve damage shuts down the body's functions, eventually leaving

victims comatose. Death comes fast, frequently within two or three

years. Girls aren't affected, though some adult women develop a

milder, nonfatal form of the disease.

Dr. Moser told the Odones nothing could be done. He'd conducted an

experiment with an extreme low-fat diet, but it hadn't worked. Bone-

marrow transplants offered some hope of rejuvenating damaged cells,

but not for patients with symptoms as severe as Lorenzo's. The doctor

said he could try slowing the disease by suppressing Lorenzo's immune

system, but there was no evidence to suggest it would work.

" I wanted to find a way, " recalls Mr. Odone, whose English is still

accented by his Italian heritage. " Who was I? A fool parent. "

Mrs. Odone, a New York native who majored in French in college, was

even more determined. Together, the couple began learning about the

latest ALD research. They bought a medical dictionary and some

biology textbooks. They called college friends who were doctors. They

asked Dr. Moser to organize a meeting of the world's leading experts

and offered to help pay with $30,000 from their savings.

It was unusual for parents to thrust themselves into the world of

scientific research, but Dr. Moser says he encouraged the Odones.

He'd spent much of his career studying a rare disease and welcomed

the help.

He was amazed at how many of the world's leading ALD experts agreed

to attend the Odones' meeting on short notice. The session was held

in 1984 at the Kennedy Krieger Institute. " He had a remarkable

capability of getting people excited about things, " the doctor says

of Mr. Odone.

The Odones learned about research regarding oleic acid, which reduced

the level of certain fatty acids in the bloodstream. It hadn't been

tried in humans, in part because it was difficult to find a

laboratory willing to make large amounts palatable for human

consumption.

But the couple was impatient. Within months of his diagnosis, Lorenzo

was bedridden and uncommunicative. Applying charm and money, Mrs.

Odone found a small lab in Ohio that could render oleic acid as an

oil. It looked like salad dressing. Dr. Moser helped the couple

settle on a dosage. They mixed some with Lorenzo's food -- he ate

mostly pureed spaghetti, carrots, potatoes and celery -- spooning it

into his mouth.

The results of blood tests at Dr. Moser's lab astonished them: The

fatty acids in Lorenzo's blood, while far from normal, had fallen by

50%. Dr. Moser was encouraged. But he reminded the Odones that the

results meant little because there was no apparent change in

Lorenzo's brain function.

After poring over medical journals and talking to doctors, Mr. Odone

developed a theory that oleic acid worked best in combination with

other acids. He decided to add one-part erucic acid, a rapeseed

extract, to four parts oleic acid. In 1986, they gave the new mixture

to Lorenzo and his fatty acids returned to normal. His condition,

however, didn't improve.

In the summer of 1987, word reached a and Ron Brazeal of

Sycamore, Ill. The Brazeals had lost one son to ALD and had another

who was bedridden as a result of the disease. They founded an

advocacy group for parents, the United Leukodystrophy Foundation.

Although Lorenzo showed few visible signs of improvement, the Odones

asked Dr. Moser and the Brazeals to publish an article about the

mixture in the ULF newsletter.

Dr. Moser had been encouraging the Odones' research, but he told the

Brazeals the oil probably didn't have any tangible benefits, both

sides recall. Dr. Moser didn't want to raise false hopes. He also

worried about some studies suggesting that erucic oil might cause

heart damage. The Brazeals, bowing to the wishes of Dr. Moser and

their group's medical advisory board, told the Odones they wouldn't

publish.

The rejection incensed the Odones, who formed a rival group to

promote ALD research. They called it the Myelin Project, for the

nerve coating destroyed by ALD. If they could find a way to restore

the myelin in Lorenzo's brain, the Odones thought he would get

better. Soon the Odones' Myelin Project and the ULF were competing

for members, money and attention.

In September of 1987, Dr. Moser felt compelled to make the separation

formal. He sent a private letter to the Odones, in which he wrote: " I

must dissociate myself from the public awareness and fund-raising

program in regard to adrenoleukodystrophy that you are now

undertaking. "

But the Odones had taken their story to the media, a tale of parents

with no medical expertise who believed they were on the verge of

curing their fatally afflicted son. , an Australian

filmmaker, picked up on one account and thought the story should be a

movie. He cast Nick Nolte and Sarandon to star as Mr. and Mrs.

Odone.

As the Odones became media celebrities, Dr. Moser watched in despair.

" I hated it, " he says now. " had dedicated my whole energy to this

disease and the papers were saying these parents had discovered

something everybody else had missed. That hurt the most. "

When reporters asked about the oil's promise, he said he was still

running tests. When peers asked privately about the oil, he says he

told them, " I don't think it does anything for anyone. "

Dr. Moser was in fact studying Lorenzo's Oil. He sought and received

special permission from the Food and Drug Administration to

administer the oil to boys with ALD, even though it hadn't been

formally tested. Dr. Moser had become convinced that the heart damage

reported in mice wouldn't occur in humans.

He didn't expect the oil to reverse damage done to boys who had

already developed symptoms. But he maintained hope that it would

delay or prevent the onset of the disease in those not yet stricken.

Within the ALD community, a black market developed among parents

whose children weren't eligible to enroll in Dr. Moser's study.

With the movie " Lorenzo's Oil " moving into nationwide release in

January 1993, Dr. Moser and his wife, Ann, flew to Chicago to attend

a showing. The Brazeals joined them. Dr. Moser wasn't consulted on

the movie and says he didn't know what to expect.

Sitting three rows from the back of the theater, the couples chuckled

at what they saw. Ustinov, portraying a character based on Dr.

Moser, had mastered the doctor's accent and his way of waving his

hands as he speaks. " He made a perfect imitation of me, right? " Dr.

Moser says now. " Except that I never wear bow ties. "

But as the movie continued, Dr. Moser grew angry. In one scene, Ms.

Sarandon, as Mrs. Odone, called the doctor a " wretched man " who " does

absolutely nothing. " At another point in the film the doctor declared

to the Odones: " I will have nothing to do with your oil. "

Even more upsetting to Dr. Moser was the movie's conclusion, in which

Lorenzo's improvement is portrayed as both clear and remarkable. He

blinks in response to his mother's questions and helps choose stories

to be read to him. As the credits rolled, the movie showed healthy

real-life boys extolling the virtues of Lorenzo's Oil. In reality,

some of the boys shown carried the gene but hadn't developed

symptoms. (About half of ALD carriers don't develop the childhood

disease but instead get a milder affliction in adulthood.)

After " Lorenzo's Oil " opened in theaters, the treatment was no longer

a modest experimental approach to a little-known disease. Reviews

were glowing. The New York Times called it " completely gripping. " Pop

star Phil recorded a song called " Lorenzo " that included the

line, " Dark shadows, sounds of thunder raging over me, came this

monster called 'A-dre-no-leu-ko-dys-tro-phy.' "

Dr. Moser defended himself in letters to several newspapers,

magazines and the FDA. " As a work of fiction, 'Lorenzo's Oil' would

be a marvelous movie, " he wrote in the medical journal, the Lancet.

Unfortunately, he continued, it exaggerated the effects of the oil

and exaggerated or invented conflicts between him and the family.

He saw the Odones shortly after the movie's release when he agreed to

appear with them on CNN. Dr. Moser says he sat calmly through the

first half of the program, but by intermission he was furious. In the

second half of the show, he says, he lost his temper and called the

movie " an abomination. "

After the taping, Mr. Odone " somewhat apologized, " Mr. Moser recalls,

blaming the movie's director for portraying the story as a battle

between loving parents and the heartless medical establishment. Mr.

Odone confirms the interaction but says he didn't back down from his

initial conclusion: " If inquiries are promising, no matter how

preliminary, the product should be given, particularly when the

disease is absolutely certain to be mortal. " Mr. , the

filmmaker, didn't respond to requests for comment.

In the years that followed, the Odones and Dr. Moser barely saw each

other aside from occasionally running into each other at medical

conferences. The Odones sent Lorenzo's blood samples to Dr. Moser's

lab but started taking their son to another neurologist for

examinations. " We did not trust each other, " Mr. Odone says.

The Odones continued to feed the oil to Lorenzo, now a teenager,

while providing round-the-clock care, paid for by their insurance, in

their Fairfax, Va., home. His condition was unchanged. Mr. Odone

yearned to go home to Piedmont, Italy, but Lorenzo couldn't be moved.

Mrs. Odone was overwhelmed at times by the stress, her husband says.

She taped notes to cabinets and walls instructing nurses on how to

perform countless tasks such as making Lorenzo's soup and cleaning

his humidifier. She fired dozens of nurses. A devout Catholic, she

found a priest willing to give her Mass over the phone because she

didn't want to leave the house.

In the summer of 1999, Mrs. Odone was diagnosed with lung cancer. She

didn't attend check-ups and rejected some treatment because she

couldn't bear to be away from Lorenzo, her husband says.

As she grew sicker, Mrs. Odone began phoning Dr. Moser several times

a week asking about the side effects of certain cancer-related tests.

The phone calls were the first substantive communication between the

doctor and the Odone family in years. In the past, the doctor and

Mrs. Odone had clashed. Mrs. Odone was so focused on curing her son,

Dr. Moser said, that she showed little interest in broader

applications of the research on ALD.

Now, Mrs. Odone confided to Dr. Moser her fears that Lorenzo's care

would suffer when she died. " I was just so totally impressed with

her, " the doctor says.

A few days after their last phone conversation, Dr. Moser read Mrs.

Odone's obituary in the Washington Post and sat down to write a

letter of condolence to Mr. Odone. The doctor praised Mrs. Odone for

her work and promised to keep working toward their common goal of a

cure. " It was only a few paragraphs, but it was very, very nice, " Mr.

Odone recalls. " He made an opening. I called him and I said, 'Of

course, Hugo, I will be with you all the way.' "

Despite the thaw, Dr. Moser still had little hope that Lorenzo's Oil

would help even boys who showed no symptoms of the disease. For

years, he had been tracking dozens of such patients taking the oil,

but at the very beginning of the trial, one had become sick and died.

In 2002, Dr. Moser was asked to present results from the study, which

is still under way, at a symposium in Belgium. But as he began

analyzing the data, he detected a surprising pattern. Among boys

taking Lorenzo's Oil and maintaining low-fat diets, a greater number

than he had expected remained healthy. But then why, Dr. Moser

wondered, had that one boy died?

He looked again at the earliest available brain scans. This time, he

detected subtle signs of brain damage he'd missed before. That meant

the boy was sick before he'd started using the oil, and his death,

therefore, was not a strike against it.

Dr. Moser called Mr. Odone to tell him the news but began by

insisting he not alert the media. The doctor didn't want to raise

expectations the way he thought the movie had. He wanted to crunch

his numbers again, and if they held up, publish the results in a

scientific journal. Mr. Odone agreed.

A few months later, the men met at the Belgium conference. They

hadn't seen each other since Mrs. Odone's memorial service and Dr.

Moser thought the usually gregarious man seemed lonely. Dr. Moser was

hobbled by a knee injury at the time. As they walked to dinner, Mr.

Odone held the doctor's elbow.

Dr. Moser presented the results of his study, which he described as

preliminary. A few months later, the men met at a conference in Italy

sponsored by Mr. Odone's Myelin Project. The two were talking when

Dr. Moser blurted out a question: Would Mr. Odone agree to co-author

his paper on the study? He hadn't given any thought to the matter

before asking, he said. Dr. Moser says he acted out of respect for

Mr. Odone's scientific contributions, not out of guilt.

As they worked on the study, the pair communicated several times a

week. Mr. Odone teased the doctor about his earlier skepticism, but

Dr. Moser didn't reply. " I am not a joking person, " he says. " I would

like to be. " The work, Mr. Odone said, " cemented our newfound

friendship. "

The study, written by Dr. Moser, Mr. Odone and 11 others, was

published in the July issue of Archives of Neurology. Dr. Moser's

name was first on the list of authors, the spot usually reserved for

the scientist who performed the bulk of the research. Mr. Odone was

listed last, in the spot often reserved for a special honoree.

The report said Lorenzo's Oil seemed to reduce the likelihood that

boys with the genetic marker for ALD would develop the debilitating

form of the disease. Of 89 boys tested, 66, or 74%, remained well.

Without the oil, the paper said, only half the boys would have been

expected to remain well. Mr. Odone was especially pleased with the

paper's conclusion and its recommendation that all boys with

asymptomatic ALD receive Lorenzo's Oil.

Dr. Moser's study wasn't perfect, partly because it relied on a small

statistical sample and partly because it included no control group in

which children received placebos. The FDA -- as it does on occasion --

gave Dr. Moser approval to work without a control group to avoid

unnecessary loss of life. Also problematic: Some of the boys who

remained healthy might have done so without the oil. Some or all

could develop the adult form of ALD.

Asked if the study is a validation of the oil, Dr. B. Rizzo,

a professor at the University of Nebraska, and one of the first to

study the effects of oleic acid on ALD, says: " I'm not 100%

convinced, because the study's design is flawed. But I think it is. I

hope it is. " One cause for optimism: Kids who hewed closest to the

low-fat diet were more likely to stay healthy.

Last year, Mr. Odone began suffering memory loss, confusion and

difficulty walking. Doctors initially suspected he was suffering from

Parkinson's Disease. Dr. Moser helped arrange for Mr. Odone to see a

specialist and he was diagnosed with a less-serious condition: Normal

Pressure Hyrdrocephalus, an accumulation of fluid that causes parts

of the brain to enlarge.

After surgery, in a rash of bad luck, Mr. Odone suffered a bad fall

and then developed pneumonia. He's confined to a wheelchair much of

the time now and attends daily physical therapy sessions at the

Kennedy Krieger Institute, the same building where Dr. Moser works.

Most days, Dr. Moser takes the elevator two floors down from his

office and chats with Mr. Odone during the sessions.

Lorenzo continues to receive daily doses of the oil. He is 27 years

old now, a grown man with thick sideburns and bushy eyebrows. On a

typical day, he lies cocooned in a blanket in the living room. A

poster from his movie hangs on a wall behind him. Sometimes, a

volunteer reads stories aloud, but Lorenzo makes no response.

By all medical reckoning, Lorenzo should have died years ago. Whether

he's sustained by the intensive care or by the oil treatment is

anyone's guess. Mr. Odone continues to hope for a cure for his son.

Even though he thinks it helps those without symptoms, he knows the

oil isn't the answer for Lorenzo. Dr. Moser has moved on to his next

goal: to develop a simple, inexpensive blood test to detect ALD in

newborns.

Sitting in the kitchen of his home with Dr. Moser recently, Mr. Odone

said he gets great pleasure from the fact " that so many boys have

been saved and so many more are going to be saved. " He looked at the

doctor for confirmation. Even though Dr. Moser thinks more tests need

to be conducted, he nodded in agreement.