In Vivo Gene Therapy in AMN
Dr. Florian Eichler | Harvard School of Medicine
Dr. Eichler is an Associate Professor of Neurology at Massachusetts General Hospital (MGH) and Harvard Medical School. His career has been dedicated to advancing the care and treatment for devastating neurogenetic conditions. Following neurogenetics training at Johns Hopkins with the late Dr. Hugo Moser and residency in pediatric neurology at MGH, he became the Director of the Leukodystrophy Service that cares for patients with an increasing variety of neurogenetic conditions. Dr. Eichler runs a laboratory at MGH that explores the relationship of mutant genes to specific biochemical defects and their contribution to neurodegeneration. In 2015, he became Director of the Center for Rare Neurological Diseases at MGH. The Center aims to eradicate rare disorders of the nervous system by leveraging the power of biological insights towards design and implementation of clinical trials. Dr. Eichler is the principal investigator of several NIH-funded studies on neurogenetic disorders as well as a gene therapy trial of adrenoleukodystrophy. For this work, he received the Martin Research Prize from MGH and the Herbert Pardes Clinical Excellence Award from the Clinical Research Forum. Dr. Eichler also serves as chair of the Rare Disease Think Tank at MGH and is founder and president of the international consortium ALD Connect, a patient powered research network that is dedicated to curing adrenoleukodystrophy.
Biomarkers for Adrenoleukodystrophy (ALD)
Dr. Troy Lund | University of Minnesota
Dr. Troy Lund and his lab manage the largest biorepository in the world for patients with the cerebral form of adrenoleukodystrophy (ALD). They utilize both mouse models and human studies to study the initiation of disease, the role of the blood-brain-barrier, and the mechanism of bone marrow transplant in treating the cerebral form of ALD. These studies are all tied to the hematopoietic system. In ALD, he has advanced the field by identifying new biomarkers to better understand how the genotype of ALD is related to the phenotype of disease as well as the critical role of early diagnosis and disease-specific neuroimaging. Dr. Lund is a co-investigator on all protocols to treat ALD with hematopoietic cell transplant at the University of Minnesota
Translation Research in ALD
Dr. Stephan Kemp | Amsterdam UMC | The Netherlands
Dr. Kemp (geneticist/biochemist) and Dr. Engelen (pediatrician/neurologist) are the principal investigators the ALD research group. They are following the largest ALD cohort worldwide. The aims of their research are to understand the natural history of ALD, develop new and sensitive clinical endpoints for clinical trials and identify predictive biomarkers. In 2015, the Amsterdam UMC was designated the national expert center for ALD. They also maintain the ALD mutation database at www.adrenoleukodystrophy.info. In 2015, they successfully nominated ALD for addition to the Dutch newborn screening program. Dr. Kemp is the project leader of the SCAN study; the pilot for implementing ALD newborn screening in the Netherlands
Imaging Methods & Evaluation of Lorenzo’s Oil in ALD
Dr. Gerald Raymond | Johns Hopkins
Dr. Gerald Raymond’s research laboratory focuses on the study of adrenoleukodystrophy (ALD) and other neurogenetic conditions. Dr. Raymond’s lab is developing new tools to diagnose, manage, and treat all aspects of ALD and improve the lives of affected boys, men, and women with this condition.
ALD Model in Zebrafish
Joshua Bonkowsky | University of Utah
Dr. Josh Bonkowsky is Division Chief of Pediatric Neurology at the University of Utah and the medical director of the Primary Children’s Center for Personalized Medicine in Salt Lake City, Utah. His lab uses zebrafish, a model organism with a readily manipulated genome, to study leukodystrophies, their mechanisms of action and possible therapeutic interventions. The group characterized an ALD model in zebrafish which phenocopies correlates of the human disease, including locomotor deficits and increased VLCFA levels. These animals also display abnormalities in early CNS development. Work is now underway to develop a cerebral ALD model and investigate the role of inflammation in this model.
Neonatal Screening for ALD
Ann Moser | Moser Center for Leukodystrophies, Kennedy Krieger Institute
Moser’s focus is to develop a neonatal screening test for X-linked adrenoleukodystrophy (ALD) by using the newborn blood spot that is collected on all US babies at birth. In December 2008, together with the MD State Newborn Screening Laboratory, we started a pilot study screening for ALD in 5000 newborns born in the local Baltimore hospitals. Ann Moser received a bachelor’s degree in biochemistry in 1961 from Radcliffe College. During the time she was an undergraduate, she was a technician in Dr. Konrad Bloch’s laboratory at Harvard University. After working as a technician in laboratories in different hospitals, Moser joined the John F. Kennedy Institute (later Kennedy Krieger Institute) in 1976 as a senior technician. In 1982, she became an assistant in neurology. Since 1991, Moser has been working as a research associate in neurology. She is a co-director of the Peroxisomal Diseases Laboratory in the Hugo W. Moser Research Institute at the Kennedy Krieger Institute.
A Therapeutic Approach in AMN mice
Dr. Klaus-Armin Nave & Dr. Celia Kassman | The Max-Planck Institute of Experimental Medicine | Germany
This lab generated a mouse model of human ALD with a null mutation in the Abcd1 gene. Similar to human ALD patients these mice display impaired peroxisomal beta-oxidation and accumulation of VLCFA in brain and adrenals. However, they lack neurological symptoms, and have a normal life-span. The data suggested that VLCFA accumulation by itself is insufficient to trigger demyelination or neurodegeneration in mice. Other environmental, genetic, and/or epigenetic factors may be involved in disease development. *Winners of The Myelin Project’s 2010 Augusto Odone New Investigator Award*