Research on adrenoleukodystrophy : looking back on Pr. Hugo Moser’s career



Written on Thursday 4 April 2013

Hugo Moser, recognized adult neurologist, dedicated all his life to  adrenoleukodystrophy (ALD) and worked tirelessly to help patients and their families. Ann Moser, his widow, and Pr. Gerald Raymond, his righ-hand man and trainee, look back on his career. 

 

What discoveries arising from Dr. Moser’s work lead to the implementation of the first diagnostic test for ALD?

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“.

In the early 80’s, the focus of primary research became the peroxisomal disorders. It had been determined that the brains of individuals with adrenoleukodystrophy (ALD) had unusual lipids – saturated very long chain fatty acids (VLCFA). Latching on to this, the Mosers showed that this could be measured in fibroblasts and in plasma. Since the development of this plasma VLCFA assay, it has been used to diagnose thousands of individuals and became one of the primary tools in the diagnosis of other peroxisomal disorders.

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.

 

Dr. Moser also developed different types of therapies for patients with ALD. Can you briefly present them? 

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 of very long chain fatty acids, they could not be reduced simply by dietary means. 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.

Worldwide, investigators embarked on a number of open studies that demonstrated despite normalization of VLCFA that the tragic course of cerebral inflammatory disease was unaffected. Again, other studies published in the early 90’s did not show appreciable change in individuals with adrenomyeloneuropathy, the adult form of the condition leading to an opinion that the agent was ineffective in ALD.

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. The results of this study while limited, did lead to reevaluation of the use of Lorenzo’s oil as a preventative therapy and to investigate it in a placebo-controlled double blind study in adrenomyeloneuropathy.

He was also involved in the first use of bone marrow transplantation in X-linked adrenoleukodystrophy at the Johns Hopkins Hospital.  While this attempt was not successful, others were not deterred and in 1990, Professor Aubourg reported the successful transplantation of an individual with early disease.

Other attempts at therapy would continue including trials with beta-interferon, thalidomide, and 4-phenylbutyrate. There were also extensive studies performed in collaboration on the natural history of ALD including progression of disease in men and women, the use of neuroimaging, and attempts to study the neuroinflammation seen in cerebral disease.

 

How did these discoveries impact the lives and care of the patients?

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 always impatient with the lack of treatment for ALD and he worked tirelessly to advocate for the affected individuals and their families. He would personally take calls, respond to emails, and write letters to assist individuals. Visitors were always welcome whether they were physicians, researchers, or families. One of the most important strengths of Dr. Moser’s career was the wide ranging network he created of scientists and families all working toward a common purpose.

 

What legacy was left by Dr. Moser?

His most recent endeavor was to get testing for adrenoleukodystrophy 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, developed a methodology using tandem mass spectroscopy that will be adaptable for newborn screening.

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