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Hugo Moser, 82; neurologist's portrayal in `Lorenzo's Oil' belied his real character

January 26, 2007|Thomas H. Maugh II | Times Staff Writer

Dr. Hugo Moser, the prominent neurologist who was vilified in the movie "Lorenzo's Oil" but who was known as a compassionate and energetic researcher by the parents of hundreds of children with the rare neurological disease known as adrenoleukodystrophy, died Saturday at Johns Hopkins Hospital in Baltimore after a long battle with pancreatic cancer. He was 82.

Moser identified the biochemical abnormalities underlying a family of 15 closely related genetic disorders, the best known of which is adrenoleukodystrophy, or ALD. He and his wife -- Ann Boody Moser -- developed a screening test for diagnosis of ALD, tested potential treatments and were refining a screening test for newborns at the time of his death.

But he probably is best known to the public from Peter Ustinov's portrayal of him in the movie as an arrogant, obstinate physician who resisted the efforts of Lorenzo's parents, Augusto and Michaela Odone, to develop a treatment for the disease -- a portrayal that he later called "an abomination."

Moser and Augusto Odone eventually reconciled -- Michaela died in 1999 -- and Odone was listed as a co-author of a 2005 paper which demonstrated that Lorenzo's oil provides at least some benefit in staving off the disease in boys who have not yet developed symptoms.

After Moser's death, Odone said he was "not only a brilliant partner in ALD research, but a dear friend whose support has been invaluable to our family all these years."

ALD, which affects about one in every 20,000 males, is one of a family of genetic disorders that affect the peroxisome, an organelle that cells use to dispose of certain chemicals that build up during the metabolism of food.

Researchers have identified at least 640 genetic mutations that alter the peroxisome membrane so that critical enzymes cannot enter to destroy a family of molecules called very long-chain fatty acids.

As the fatty acids build up in the blood and the brain, they impair the production of myelin, the protective sheath that covers nerve fibers. Nerves then short-circuit, producing symptoms that include seizures, loss of muscle control, adrenal insufficiency (Addison's disease) and speech, vision and hearing problems. In the most severe forms, such as ALD, the disorders often are fatal.

Moser had been working on ALD and related disorders since 1955, toiling most of that time in anonymity. He and his wife developed the first blood plasma screening test to identify the disorders -- an important achievement because many forms of the disease are often misdiagnosed as multiple sclerosis.

"Once we developed the plasma assay, literally thousands of patients came out of the woodwork," he said recently.

At first, he had little to offer the newly diagnosed patients.

His team had spent long years untangling the biochemical abnormalities behind the disorders and had tested several potential drugs, but none seemed to provide any benefit. One treatment he tested that was useful was a bone marrow transplant, but that helped only boys in the earliest stages of the disease, before their myelin had been irreversibly damaged.

Along the way, he published about 350 journal articles and 100 book chapters about his research on metabolic disorders and the care and treatment of children with developmental disabilities.

The 1992 movie, however, pulled him into the public consciousness. "The film had a huge impact in making people aware of the disease," he said. Unfortunately, it also overstated the benefits of the oil, and the medical community "became dubious about the whole idea. As a result, our first grant applications to test the oil were turned down."

The film tells the story of the Odone family, who were shocked when their bright, exuberant, 5-year-old son Lorenzo suddenly began to deteriorate, losing the ability to walk, see and speak.

Although they were not scientists, the parents researched the disease and, according to the movie, eventually developed a treatment called Lorenzo's oil. The oil is a mixture of oleic acid and erucic acid -- fatty acids found in olive and rapeseed oils.

Lorenzo's oil is thought to work by tying up enzymes that produce the very long-chain fatty acids, preventing their synthesis. Initial studies showed that daily administration of the oil lowered blood levels of those fatty acids to normal.

Lorenzo, who turned 28 last year, has been taking the oil ever since. He is still blind, mute and confined to bed, nearly immobile, but Augusto Odone attributes his survival to the treatment.

The actual story was somewhat more complicated.

The idea that oleic and erucic acids could be beneficial was actually developed by Dr. William B. Rizzo of the Medical College of Virginia, who demonstrated in a laboratory that they could prevent cells from making the long-chain acids.

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