In Vivo Gene Therapy in AMN
Dr. Florian Eichler | Harvard School of Medicine
In partnership with the Cure ALD Foundation, we granted $50,000 to Dr. Florian Eichler’s pilot study of gene therapy in adrenomyeloneuropathy (AMN). Dr. Eichler and his team have established an AMN animal model proof of concept showing a gene therapy approach could provide benefit where no treatment is currently available. Currently, when young men with adrenoleukodystrophy (ALD) begin showing adult-onset signs of AMN, they slowly lose their ability to walk. This pilot will help move Dr. Eichler’s research program forward towards human studies.
Imaging Methods & Evaluation of Lorenzo’s Oil in ALD
Dr. Gerald Raymond | University of Minnesota | USA
In late 2015, we granted $25,000 to Dr. Gerald Raymond’s research laboratory at the University of Minnesota which focuses on the study of X-linked adrenoleukodystrophy (ALD) and other neurogenetic conditions. In collaboration with the Inherited Metabolic and Storage Disease Bone Marrow Transplantation Program, the Center for Orphan Drug Research, the Center for Magnetic Resonance Research, and others, 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.
Biomarkers for Adrenoleukodystrophy (ALD)
Dr. Troy Lund, PhD, MD | University of Minnesota | USA
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
Schwann Cell Transplantation for Multiple Sclerosis
Dr. Timothy Vollmer | Yale University School of Medicine | USA
One of the earliest research projects we funded was the transplantation of one million myelin-forming cells into the brain of a Multiple Sclerosis patient, a first in medical history. The trial was led by Dr. Vollmer and was financed entirely by The Myelin Project. This first patient recovered well from the procedure. Although no clinical improvement observed (probably because of the small number of cells transplanted), neither did it worsen. Thus the procedure itself was confirmed as safe. The first-ever attempt to transplant myelin-producing cells in the human CNS, the Yale trial showed the surgical procedure to be safe, with none of the patients suffering adverse side effects from the transplantation. This result was largely unexpected-many researchers believed that operating in the MS brain was too risky and that it would exacerbate the subjects’ condition. But that did not occur. As mentions of the trial filter into journal articles, several researchers, both within and outside of The Myelin Project Work Group, have taken note of the safety of the transplantation procedure. Now that safety is no longer an issue, other researchers are likely to replicate the transplantation trial with Schwann cells or other cell types.
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*
Neonatal Screening for ALD
Ann Moser | Moser Center for Leukodystrophies, Kennedy Krieger Institute | USA
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.
Lentiviral Gene Transfer in Krabbe’s Disease
Ian Duncan, Ph.D. | University of Wisconsin | USA
The core research area of this laboratory is myelin. Myelin is the insulator of axons and is essential for normal impulse transmission in the nervous system. We are interested in both the development of myelin in the central nervous system (CNS) and how myelin is targeted in acquired disorders of the CNS, in particular in multiple sclerosis (MS). To explore both development and disease of myelin, we use a variety of models, including animals with mutations in myelin genes (the myelin mutants), to study both the genetic control of myelin formation and maintenance and myelin repair. We are especially interested in cells that could be transplanted into the CNS to repair areas of myelin disease.
Bone-marrow derived cells for Multiple Sclerosis (MS) Treatment
Professor Neil Scolding, FRCP PhD | Institute of Clinical Neurosciences | UK
About 30 years ago, investigators began to think that cell therapies might be useful to treat loss of myelin caused by multiple sclerosis (MS). The disease has proved more complex, and tissue repair in the brain and spinal cord more challenging than we first thought. Many factors contribute to myelin and nervous tissue damage in MS. Cells capable of myelin repair are present in damaged areas but nonetheless do not seem to repair myelin. This might mean that simply adding more myelin-making cells to lesions won’t be enough to help in this disease. Professor Scolding is studying bone marrow derived stem cells. These have a very limited capacity for turning into myelin forming cells. But they seem to stimulate repair processes that are key to tissue regeneration in MS. A small safety study of these cells in six patients with chronic MS is nearing completion. The final report will be made when the data analysis is finished. Dr. Scolding has said, “We are grateful indeed to the Myelin Project for our funding, without which this trial would have proved very difficult to complete.”