CSF Bio-markers for Adrenoleukodystrophy (ALD)
University of Minnesota
Troy C. Lund, PhD, MD
"We expect to find new and novel proteins found in the CSF of boys with cALD that are greater in abundance than control samples. Based on preliminary data, we anticipate that the number of protein hits to be in the 300-5-- range. A large number of these proteins will show differential expression between cALD and control samples.
The approach described in this proposal will allow for the identification of new and novel proteins which could be predictors of disease status, disease progression, or outcome after therapy (which currently involves hematopoietic cell transplant) when combined with clinical statistics in our database. Identified proteins may also become robust biomarkers for other conditions such as adult cALD or AMN."
Roles of microglia macrophages and their therapeutic use in combination with lentiviral gene transfer in Krabbe’s Disease
Ian Duncan, Ph.D.
University of Wisconsin, Madison, Wisconsin USA
Chairman of The Myelin Project's Scientific Advisory Panel
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.
Newborn Screening of
The Kennedy Krieger Institute
707 North Broadway, Baltimore, MD 21205 (800) 873-3377
Internationally recognized for improving the lives of children and adolescents with disorders and injuries of the brain and spinal cord, the Kennedy Krieger Institute in Baltimore, MD serves more than 11,000 children each year through inpatient and day treatment programs, outpatient clinics, home and community services and school-based programs.
Kennedy Krieger provides a wide range of services for children with developmental concerns mild to severe, and is home to a team of investigators who are contributing to the understanding of how disorders develop and pioneering new interventions and earlier diagnosis. For more information on Kennedy Krieger Institute, visit www.kennedykrieger.org.
Peroxisomal proliferation and degeneration -
A therapeutic approach in AMN mice
Dr. Klaus-Armin Nave
Dr. Celia Kassmann
The Max-Planck Institute for Experimental Medicine | Gottingen, Germany
In x-ALD, mutations of the ABCD1 gene lead to impaired oxidation of VLCFA in virtually all cell types. Inactivation of the homologous gene in the mice shows a very late onset neuropathy starting at 16 months that is reminiscent of Adrenolmyeloneuropathy (AMN), the adult onset of of x-ALD. We have 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.
Histological as well as ultrastructural analysis did not reveal obvious myelin pathology. Our data suggest 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. For more information, click here. *Winners of The Myelin Project's 2009-2011 Augusto Odone New Investigator Award*
Kennedy Krieger Institute
707 North Broadway, Baltimore, MD 21205
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.
Bone-marrow derived cells for the treatment of Multiple Sclerosis (MS)
Professor Neil Scolding, FRCP PhD
University of Bristol Institute of Clinical Neurosciences, U.K.
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.”
Schwann Cell Transplantation
for Multiple Sclerosis patients
Yale University School of Medicine
15 York Street New Haven, CT 06510
On July 19, 2001, members of The Myelin Project Work Group took a great leap forward when they transplanted one million myelin-forming cells into the brain of a Multiple Sclerosis sufferer, 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.
The Odone Research Fund at the KKI
Augusto was a remarkable man who, after his young son, Lorenzo, became ill with X-linked adrenoleukodystrophy (ALD), sought to find a cure for this devastating, rapidly progressive neurological disease. Augusto, by trade an economist who worked for the World Bank, immersed himself in medical literature, studied the metabolism of fatty acids, and invented a formulated oil mixture—now known as Lorenzo's Oil—that he used as a dietary supplement to slow his son's disease. After more than 20 years, Lorenzo's oil is still being used to prevent the neurological disease in hundreds of asymptomatic ALD boys.
After the deaths of Michaela in 2000 and Lorenzo in 2008, Augusto continued his international support of research on ALD and other leukodystrophies. We honor his life, as well as his commitment and dedication to finding treatments for these neurological disorders. In his honor, we have established the Odone Fund for research on ALD at Kennedy Krieger Institute. Click here for more information.