Progress Report: Dr. Florian Eichler’s AMN Gene Therapy Pilot Study

Last year, The Myelin Project (in partnership with the Cure ALD Foundation) granted $50,000 to Dr. Florian Eichler’s pilot study of gene therapy in adrenomyeloneuropathy (AMN).

Dr. Eichler and his team  established an AMN animal model proof of concept showing a gene therapy approach could provide benefit where no treatment is currently available. This pilot will help move Dr. Eichler’s research program forward towards human studies.

We received the following update from Dr. Eichler:


“We have now gone beyond our first paper (Gong et al 2015) describing proof of concept that we can deliver AAV9-mediated gene therapy to brain cells in cell culture and a mouse model of AMN and thereby lower VLCFA. After finding that we got into the right cell types (glial cells, microglia, endothelial cells) that normally express ABCD1, we tested different routes of delivery.

We found that while distribution after direct delivery into the brain ventricles was not optimal, behavior of the AMN mice was better compared to after IV delivery. We therefore developed a method for delivery into CSF from the lumbar spine area (similar to a spinal tap). This seems to lower VLCFA in spinal cord. FDA reviewed our data and is encouraging us to move forward with toxicity and biodistribution studies

Our current challenge is to better define clinical trial end points for AMN. In a small unfunded pilot study we are defining variability of balance measures in AMN patients but also aiming to address other needs in preparation for trials.”


Objectives: The success of gene therapy for AMN depends on targeted delivery and optimized outcome measures. We aim to (1) compare the biodistribution of ABCD1 after AAV9-mediated delivery to that of endogenous expression in wild-type mice, and (2) examine the test-retest variability of walking and balance measures in AMN patients.

Methods: (1) Perform immunohistochemistry across different spinal cord levels (cervical/thoracic/lumbar) to determine which cell types express ABCD1 and compare the distribution to that after intrathecal AAV9-mediated ABCD1 delivery. (2) Assess 25 foot and 6-minute walk test as well as sway amplitude on force plate on subsequent day measurements in 10 patients with AMN.

Relevance to the Leukodystrophies: This treatment will address unmet need and further help advance intrathecal approaches for other leukodystrophies.

Dr. Florian Eichler studies the genetics of peroxisomal disorders, lipid metabolism, and spatial aspects of nuclear magnetic resonance spectroscopy. For more information about Dr. Eichler, please see the biography below.


Dr. Florian Eichler received his M.D. from the University of Vienna Medical School. After graduating in 1997, he entered residency in Pediatrics and pursued studies on cerebral blood flow and metabolism. In 1999 he won a scholarship to study in vivo MR spectroscopy in pediatric patients with metabolic and neurometabolic conditions at Johns Hopkins and joined the laboratory of Dr. Hugo Moser, dedicated to peroxisomal disorders at the Kennedy Krieger Institute. He then underwent residency training in Child Neurology at the Massachusetts General Hospital (MGH). After completing residency in 2005 he joined the staff at MGH.

Now an Associate Professor of Neurology at Harvard Medical School he is extending his research into animal models of neurodegenerative disorders. His research focus is on the genetics of peroxisomal disorders, lipid metabolism, and spatial aspects of nuclear magnetic resonance spectroscopy. As director of the leukodystrophy clinic at the MGH he sees patients with a variety of white matter disorders. He currently holds several NIH awards funding studies to analyze metabolic changes seen in the brain by MR measures and to determine the neurotoxicity of newly discovered atypical sphingolipids.

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