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May 2007

Hugo W. Moser, MD (1924-2007)

Arch Neurol. 2007;64(5):758-759. doi:10.1001/archneur.64.5.758

Hugo W. Moser used to relate the advice he had received early in his training: make it your goal to know everything about a disease. The man who would make this his directive for adrenoleukodystrophy (ALD), peroxisomal disorders, and other diseases of the developing brain died on January 20, 2007, at the age of 82.

Born in Bern, Switzerland, he spent his early childhood in Berlin, Germany. His father was an art dealer and his mother an actress. The family fled Nazi Germany in 1933 and subsequently lived in the Netherlands, Italy, Spain, and Cuba, before obtaining visas and immigrating to the United States.

Hugo W. Moser, MD

Hugo W. Moser, MD

He attended Harvard College from 1942 through 1943 but left to enter military service. He subsequently received his medical degree from the College of Physicians and Surgeons at Columbia University, in New York City, in 1948 where he also served as a medical intern at the Columbia-Presbyterian Medical Center. In 1950, he moved to Boston, Mass, and was an assistant in Medicine at the Peter Bent Brigham Hospital. He served in Korea as a medical officer in the Medical Services Corps, US Army from 1952 to 1954. He returned to study at the Graduate School of Arts and Sciences at Harvard and received his MA degree in 1955.

From 1955 to 1957, he was a research fellow in the Department of Biological Chemistry at Harvard and then in 1957 to 1960 he entered the neurology residency program under under Dr Raymond Adams at the Massachusetts General Hospital. He continued on at the Massachusetts General Hospital and Harvard eventually rising to the rank of full professor.

In 1968, he became the assistant superintendent of the Walter Fernald State School in Waltham, Mass, and then in 1974, the superintendent. He was instrumental in the creation of the Eunice Kennedy Shriver Center for Mental Retardation and served as its codirector from 1974 through 1976 until his departure to Baltimore.

In 1976, he was appointed president of the Kennedy Institute in Baltimore and professor of neurology and pediatrics at Johns Hopkins University. In 1988, ostensibly as retirement, he stepped down and undertook directorship of the Center on Research on Mental Retardation and Related Aspects of Human Development from 1988 to 1995 and then became director of the Neurogenetics Research Center from 1995 to 2007.

From the early research years, Dr Moser was involved in the study of lipid metabolism and other metabolic disorders of the brain. With his lifelong partner, his wife Ann, work was done in metachromatic leukodystrophy and multiple sulfatase deficiency. He was also involved in the determination that ceramidase deficiency resulted in Farber disease (lipogranulomatosis).

In the early 1980s, the focus of primary research became the peroxisomal disorders. It had been determined that the brains of individuals with ALD had unusual lipids–saturated very long chain fatty acids (VLCFA).1 Latching on to this, the Mosers showed that VLCFA levels could be measured in fibroblasts and in plasma.2,3 Since the development of this plasma VLCFA assay, it has been used to diagnose thousands of individuals4 and became one of the primary tools in the diagnosis of other peroxisomal disorders. The subsequent diagnosis and collection of specimens lent itself to a repository of cell lines with a variety of peroxisomal disorders that was instrumental in the stepwise determination of various genetic defects in peroxisome protein importation.

With this diagnostic test, the phenotypic variation within families with ALD could be realized and for the first time, asymptomatic individuals who were at risk for developing adrenal insufficiency and the childhood cerebral disease could be determined. With this ability, however, came the burden of now advising families that not only did their son have childhood cerebral ALD and would die of that disorder, but also the information that his younger brother had the same biochemical abnormality and was also at risk.

At the time that this understanding of the biochemical abnormality was becoming available, a promising potential treatment was also uncovered. It had been noted that while there was an elevation in VLCFA levels, they could not be reduced simply by dietary means.5 It was subsequently noted that use of monounsaturated fatty acids, a mixture referred to as Lorenzo's oil, with diet would effectively reduce blood levels of VLCFA.6,7

Worldwide, investigators embarked on a number of open studies that demonstrated that despite normalization of these VLCFA levels, the tragic course of cerebral inflammatory disease was unaffected. Again, other studies published in the early 1990s did not show appreciable change in individuals with adrenomyeloneuropathy, the adult form of the condition, thus leading to an opinion that the agent was ineffective in ALD.8

At this time, we continued the study of asymptomatic boys examining the role of the oil as a preventative therapy. In 2005, the experience was reported in the Archives of Neurology.9 Examining boys who had normal findings on magnetic resonance imaging and neurologic examination at baseline, a proportional hazards model demonstrated that lowering the level of VLCFA reduced the risk of developing magnetic resonance imaging abnormalities and therefore childhood cerebral disease.9 The results of this study, while limited, did lead to reevaluation of the use of Lorenzo's oil as a preventative therapy and to its investigation in a placebo-controlled double-blind study in adrenomyeloneuropathy.

His most recent endeavor was to get testing for ALD and other peroxisomal disorders into the panel of disorders tested in regional newborn screening. It was apparent to those of us who worked in the field that while we could try and test every at-risk family member, there were too many families who did not know that they were at risk. Hugo once again turned to his right arm, Ann, who in conjunction with Walter Hubbard, PhD, developed a methodology using tandem mass spectroscopy that will be adaptable for newborn screening.10

Hugo was dedicated to his patients and their families. He advocated and actively supported the family group for leukodystrophies, the United Leukodystrophy Foundation. He was a yearly fixture at their July meetings in Illinois sitting with families at dinner discussing their situation.

He was so proud of his own family, the accomplishments of his children, and his grandchildren. The only thing that I knew that ever moved him to leave when there was work to be done was his love of the symphony, and he was a patron of the Baltimore Symphony Orchestra. The only force that could make him do anything else than what he wanted at a particular moment was his beloved wife Ann. Their extraordinary partnership in science and life was apparent to all of us who knew them and we mourn his passing with her.

While we cannot all aspire to know and do everything for a particular disease, we are grateful that there are individuals such as Hugo Moser who could motivate a team of scientists and clinicians forward.

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Article Information

Correspondence: Dr Raymond, Kennedy Krieger Institute, 707 N Broadway, Baltimore, MD 21205 (raymond@kennedykrieger.org).

Igarashi  MSchaumburg  HHPowers  J  et al.  Fatty acid abnormality in adrenoleukodystrophy.  J Neurochem 1976;26851- 860PubMedGoogle ScholarCrossref
Moser  HWMoser  ABKawamura  N  et al.  Adrenoleukodystrophy: elevated C26 fatty acid in cultured skin fibroblasts.  Ann Neurol 1980;7542- 549PubMedGoogle ScholarCrossref
Moser  HWMoser  ABFrayer  KK  et al.  Adrenoleukodystrophy: increased plasma content of saturated very long chain fatty acids.  Neurology 1981;311241- 1249PubMedGoogle ScholarCrossref
Moser  ABKreiter  NBezman  L  et al.  Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls.  Ann Neurol 1999;45100- 110PubMedGoogle ScholarCrossref
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Rizzo  WBLeshner  RTOdone  A  et al.  Dietary erucic acid therapy for X-linked adrenoleukodystrophy.  Neurology 1989;391415- 1422PubMedGoogle ScholarCrossref
Moser  HW Lorenzo oil therapy for adrenoleukodystrophy: a prematurely amplified hope.  Ann Neurol 1993;34121- 122PubMedGoogle ScholarCrossref
Moser  HWRaymond  GVLu  SE  et al.  Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo's oil.  Arch Neurol 2005;621073- 1080PubMedGoogle ScholarCrossref
Hubbard  WCMoser  ABTortorelli  S  et al.  Combined liquid chromatography-tandem mass spectrometry as an analytical method for high throughput screening for X-linked adrenoleukodystrophy and other peroxisomal disorders: preliminary findings.  Mol Genet Metab 2006;89185- 187PubMedGoogle ScholarCrossref