Moser worked on lipid chemistry with Manfred Karnofsky, until becoming a resident in neurology at
Massachusetts General Hospital (MGH), where he established a neurochemistry program. Hugo set up the test for urinary sulfatides and compared the composition of urinary lipids with that of brain in
metachromatic leukodystrophy. Moser spent formative years in the research laboratories of the neurochemist
Jordi Folch-Pi and
Marjorie Lees at
McLean Hospital. At McLean Hospital he interviewed
Ann Boody for a position in his laboratory. This proved to be the beginning of a long and successful professional and marital partnership between the two. In the early research years, Moser and Boody worked on
lysosomal disorders. They were the first to describe the presence of cholesterol sulfate in the human brain. They further investigated the role of
steroid sulfatases in
metachromatic leukodystrophy and
multiple sulfatase deficiency, and they identified acid ceramidase as the enzyme deficient in
Farber's disease. In 1964, Moser returned to the
Joseph P. Kennedy research laboratories at MGH, and with Mary Efron and her junior faculty staff, Harvey Levy and Vivian Shih, he started screening programs for amino acid disorders and
lysosomal disorders. When training with other neurologists under Ray Adams at the
Fernald State School in
Waltham, Massachusetts, Moser became interested in providing better services for persons with developmental and physical disabilities. He was appointed research director and later superintendent of the Fernald State School. He also founded and directed the Eunice Kennedy Shriver Center for research and training in intellectual disability. During this time he became a Harvard University Professor of Neurology at MGH, and established a model of a close link between clinical practice, training and community services for the developmentally disabled and bench research.
ALD research In 1976, Moser accepted the position of president of the
Kennedy Krieger Institute and professor of Neurology and Pediatrics at
Johns Hopkins in Baltimore. Here he was able to merge areas of service, training and research. Yasuo Kishimoto, who had helped Kuni Suzuki make the discovery of elevated very long chain fatty acids in
Adrenoleukodystrophy brains at
Albert Einstein College of Medicine, followed Moser from the Shriver Center to the Kennedy Institute. With Kishimoto's help, Hugo and Ann Moser developed the first assay for ALD in
fibroblasts In 1981, they developed the
plasma assay. Moser worked with Jim Powers for many years defining the phenotypic variation in ALD. Jack Griffin, then a fellow at NIH in endocrinology, first described the adult form of ALD. Beyond establishing the diagnostic testing for
X-linked adrenoleukodystrophy, Moser also contributed to the discovery of the
gene for X-ALD. During an interview with the
American Neurological Association, he recalled how a post-doc by the name of Patrick Aubourg had come from Paris to work in his lab. Aubourg began working on the gene abnormality at Kennedy Krieger. However, it was Aubourg's work with Jean-Louis Mandel in
Strasbourg that finally led to identification and mapping of the gene. As soon as diagnostic testing was established, Moser began to fight for treatment of patients with ALD. Together with the parents’ association
United Leukodystrophy Foundation he provided support and guidance for families stricken by this devastating illness. Back in 1982, Johns Hopkins performed the first
bone marrow transplantation in ALD. However, it wasn't until Aubourg transplanted a very mildly involved patient with his nonidentical twin as a donor, that bone marrow transplantation had a successful outcome. Moser went on to collaborate a great deal with the
University of Minnesota, where Bill Krivit and Charlie Peters developed a unique method of transplantation of ALD boys. Moser's clinical partners Sakkubai Naidu and Gerald Raymond worked together with him on these clinical trials in ALD patients.
Lorenzo's oil One of Moser's longest endeavors was his work on
Lorenzo's oil. It began with his relationship with
Augusto and Michaela Odone, the parents of
Lorenzo Odone, the namesake for ''Lorenzo's oil''. Moser had diagnosed their son with the plasma assay. With the boy's subsequent decline, Moser had suggested dietary therapy and
immunosuppression, which turned out not to be successful and contributed to frustration and tension between the Odones and Moser. Together, they organized a symposium at Kennedy Krieger where Bill Rizzo presented data that showed that adding
oleic acid (C-18 monounsaturated) to
fibroblast cultures of ALD patients would reduce their
fatty acids. Odone made an independent intellectual computation – namely that the use of
erucic acid, which is C-22:1 (C-22 monounsaturated), would increase the effectiveness – and Lorenzo's oil was developed. Controlled studies, however, indicate that Lorenzo's oil is not effective at treating symptomatic ALD, although it may delay the onset of symptoms if taken before they set in. ==References==