NTSAD Research Initiative
Purpose
NTSAD’s Research Initiative strives to:
- clearly communicate disease-related research developments
- provide networking for basic and clinical scientists focused on our disorders
and funding organizations - galvanize the lysosomal storage and leukodystrophy diseases community.
NTSAD seeks to define the relevant research by understanding and communicating research already underway, by promoting the viability of current research, and by securing public and private sources of research funding.
The Research Initiative Committee is a network of committed and passionate people directly affected by lysosomal storage and leukodystrophy diseases dedicated to raising the funds necessary to vigorously pursue treatments and ultimately cure these devastating diseases.
NTSAD established the Scientific Advisory Research Evaluation Subcommittee to liaison to the scientific community in order to assess current research developments and advise the Research Initiative Committee on the leading scientific efforts. Together these committees endeavor to unite and motivate scientific and philanthropic leaders from around the world.
NTSAD solicits proposals for innovative research projects that should generate strong preliminary data for major funding in the area of genetic neurodegenerative disorders and, in partnership with other organizations or as part of a larger consortium, the Research Initiative funds research that can lead to novel treatments for lysosomal or leukodystrophy diseases impacting the central nervous system. Click here for a sample RFP.
Research as Background
With its inception in 1957, the founding families envisioned that NTSAD was to be an umbrella organization that would include not only the more prominent known disorders at the time: Tay-Sachs, a lysosomal storage disorder and Canavan, a leukodystrophy, but also related conditions posing similar clinical symptoms as well as shared familial, emotional and scientific problems. Fifty years ago, many of these “allied diseases” were not yet identified or named, but today the “allied diseases” represent a family of more than 50 genetic diseases including leukodystrophies and other lysosomal storage diseases affecting the central nervous system.
By supporting scientific research, these families wanted to find the answers to these questions:
- What causes these diseases?
- How do these diseases progress?
- Can we stop the progression?
- Can we treat the diseases? Can we cure these diseases?
- Can we prevent the diseases?
NTSAD’s support of the scientific process eventually led to some of the most exciting discoveries and firsts in genetics, including finding some of the genetic causes of disease and the resultant understanding of prevention through carrier testing, community screenings, and prenatal analysis. But significant questions about disease progression, treatment and cure remain.
Research Gains Momentum at the Turn of the Century, 2001-2003
In 2001, the organization rededicated itself to funding cutting-edge scientific and medical research and established the NTSAD Research Initiative. In 2003, NTSAD saw the culmination of several years of hard work as significant movement in the lysosomal storage disease therapeutics arena continued.
- Clinical trials of a substrate inhibitor drug now known as Zavesca®, now owned by Actelion, proceeded for Type I Gaucher disease while other trials got underway in the U.S. and the U.K. for Niemann-Pick Type C, Gaucher Type C and Late Onset Tay-Sachs. Currently FDA approved for use for Gaucher Type I and being prescribed in Europe, this novel drug continues to be tested.
- FDA approval of Fabrazyme® enzyme replacement therapy for Fabry disease brought relief for this potentially fatal lysosomal storage disorder causing renal failure, stroke, heart disease and debilitating pain. Fabrazyme is owned by Genzyme.
- Aldurazyme® an enzyme replacement therapy for MPS I also owned by Genzyme received FDA approval for the treatment of MPS I by delaying the progression of MPS I in the body systems and organs most affected by the disease.
- The number of infants receiving stem cell transplants from umbilical cord blood increased for newborns diagnosed prenatally or soon after birth with Krabbe disease. This complicated process continues to be a viable option for babies with MPS, and is still considered highly experimental for other lysosomal storage diseases.
- In early 2003, a group of children affected by Canavan disease were enrolled in a gene therapy trial at the Robert Wood Johnson Medical School Cell and Gene Therapy Center. The patients were being evaluated every three months to track the impact of this delicate procedure.
- The first clinical trials of enzyme replacement therapy for Pompe disease began in 2003 for approximately 35 children around the world. Quality of life and physical improvements were quickly seen in some of the children. A second study involving younger infants was about to begin.
- While not yet an FDA-approved medication, “Lorenzo’s Oil” continues to show positive impact in pre-symptomatic boys with Adrenoleukodystrophy.
The Pace Picks Up, 2003-2005
The broader genetic disease community and the lysosomal storage disease community in particular continue the trend toward greater collaboration at various levels. NTSAD participates in and often pioneers these therapeutic efforts in a highly visible way, working with the allied disease lay advocacy organizations and their leadership to bring about new efforts such as the Lysosomal Storage Disease Research Consortium and GOLD-Global Organisation for Lysosomal Diseases, while also participating in important dialogues with academic and medical institutions, with biotech companies focusing on treatment for these difficult disorders, and with the federal government for increased awareness and funding.
- Zavesca clinical trials for Late Onset Tay-Sachs disease continued with 30 participants at two study sites, as well as other trials for the small molecule drug with Niemann-Pick Type C and Gaucher disease.
- First clinical trial for juvenile Tay-Sachs and Sandhoff began in Toronto, Canada, while protocol developed for an unprecedented clinical study in infants in the U.S.
- In several academic laboratories around the world, scientists study the impact of varying novel approaches to conquer the blood-brain barrier on larger animal models of the LSDs, including canine MPS and feline gangliosidoses.
- The LSD Research Consortium, an unparalleled collaborative effort of patient organizations, was established in July 2004. The Consortium created a partner program with the National Institute of Neurological Disease and Stroke and the Office of Rare Diseases at the National Institutes of Health to encourage translational research for this specific group of rare diseases.
What was said at the October 2002 Annual World Symposium on Lysosomal Storage Disorders in Baltimore continues to ring true:
| Until recently, the basic biology and possibilities of treatment for lysosomal storage diseases (LSDs) were poorly understood and/or underdeveloped. The recent successes in the treatment of these diseases have rekindled an interest in expanding the knowledge base about their basic and clinical aspects. Understanding these mechanisms of disease causation will continue to lead to additional treatment options for LSDs for affected patients. |
2006 NTSAD’s Golden Anniversary, 50 years and beyond
Today research goes beyond the grant-making process and encompasses a comprehensive knowledge of global activities that may someday impact people dealing with genetic diseases of the central nervous system. NTSAD attains that knowledge base through its Scientific Advisory Committee and its Research Evaluation Subcommittee, ongoing alliances with related patient advocacy groups and umbrella organizations such as the Genetic Alliance and the National Organization for Rare Disorders (NORD).
- After several years of study it was concluded that Zavesca does not halt the progression of Late Onset Tay-Sachs, the investigation of the drug in babies and children continues.
- Niemann-Pick Type C has shown encouraging results after 12 months in adult and pediatric patients, showing improvement or stabilization of key features of the disease such as saccadic eye movements, swallowing, cognition and auditory function. These promising results warrant discussion with regulatory authorities and continuation as planned for 24 months.
- Gaucher Type III showed inconclusive results after 12 months.
- A phase I clinical trial of an acetate supplement therapy in Canavan disease is ongoing at Sheba Medical Center in Israel.
- In April FDA granted marketing approval for Myozyme® (alglucosidase alfa) in the U.S. Myozyme is indicated for use in patients with Pompe disease (GAA deficiency). Myozyme has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared to an untreated historical control, whereas use of Myozyme in patients with other forms of Pompe disease has not been adequately studied to assure safety and efficacy.
- Shire announced in July that the FDA has granted marketing approval for Elaprase, a human enzyme replacement therapy for the treatment of Hunter syndrome, also known as Mucopolysaccharidosis II (MPS II). Shire Press Release.
- Even though none of lysosomal storage disease centers were awarded grants Rare Disease Clinical Research Center from the Office of Rare Diseases in 2003, it still yielded a positive outcome because the research community convened to form the Lysosomal Disease Research Network to better position itself for future federal funding. NTSAD is an ongoing part of that effort.
- By gaining official charitable status in the United Kingdom and having an executive director in place, GOLD is moving forward on an international level and NTSAD has been part of the development of that international organization, which brings together all stakeholders, including clinical researchers, biotechnology corporate executives and nonprofit disease organizations.
- The passage of the Rare Diseases and Orphan Product Development Acts in 2002 continues to ensure that research moves forward and products are developed for rare diseases. Working closely with NORD, NTSAD’s leadership, member families, and chapters and affiliates NTSAD strongly advocated for this legislation.
NTSAD also interacts regularly and maintains important relationships with biotechnology and pharmaceutical companies that focus on the development of treatments for lysosomal storage diseases. Our scientific advisors and some of our member families are involved in prototype medical treatments such as hematopoietic stem cell transplantation using umbilical cord blood, gene therapy, substrate deprivation, and soon, pharmacological chaperone therapy. There is ever-increasing evidence that the pediatric form of diseases such as Tay-Sachs and the potential treatments for it share certain characteristics with other neurodegenerative conditions, especially adult disorders of the central nervous system such as Alzheimer’s, Parkinson’s or Lou Gehrig’s (ALS) diseases. NTSAD is dedicated to promoting common areas of research interest to advance all potential research avenues. Our involvement with research, be it basic science, translational or clinical, is the key to better understanding these rare genetic conditions and to working to bring the target patient populations closer to effective medical treatments.
2002 NTSAD Research Initiative Funded Researchers and Projects:
Bruce A. Bunnell, Ph.D.
Tulane University Health Sciences Center
“In utero Gene Therapy of Sandhoff Disease in a Murine Model”
Stephanos Kyrkanides, D.D.S., M.S., Ph.D.
University of Rochester School of Medicine & Dentistry
*"Perinatal Gene Therapy for β-hexosaminidase disorders (Tay-Sachs and Sandhoff diseases)”
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* This project was later awarded significant funding in a multi-year NIH grant – congratulations! |
Paola Leone, Ph.D.
University of Medicine and Dentistry of New Jersey
"Neuroprotective Effect of Minocycline in Sandhoff Disease"
Professor Thomas N. Seyfried, MS, Ph.D.
Boston College
“Therapeutic evaluation of NB-DGJ for ganglioside storage diseases”
2002 Research Initiative Resultant Publications
Baek, R.C., Kasperzyk, J.L., Platt, F.M., and Seyfried, T.N. N-butyldeoxygalactonojirimycin reduces brain ganglioside and GM2 content in neonatal Sandhoff disease mice. J. Neurochem. 90: (Suppl. 1) 89, 2004.
2003 Research Initiative Funded Researchers and Projects:
Jean-Pyo Lee, Ph.D./Evan Y. Snyder lab
Beth Israel Deaconess Medical Center/Burnham Institute
“Therapeutic Potential of Neural Stem Cells in the Gangliosidoses (Tay-Sachs & Sandhoff Diseases)”
Cynthia Tifft, M.D., Ph.D., FACMG
Children’s Research Institute of Children’s National Medical Center
“Comprehensive Biochemical Analysis of Cerebrospinal Fluid in Patients with GM2 Storage Disorders:
Molecular Pathogenesis of Disease Progression”
2003 Research Initiative Resultant Publications
Lee J-P, Taylor RM, Platt F, Snyder EY, Neural stem cell therapies & applications to lysosomal storage disorder in J.A. Barranger, M.A. Cabrera-Salazar (Eds), Lysosomal Storage Diseases, Plenum Press (in press).
2006 – 2007 Research Initiative Funded Researchers and Projects
Susan L. Cotman, Ph.D.
Massachusetts General Hospital
“Small molecule screening to identify modifiers of lysosomal trafficking, a putative therapy for Batten”
Doug Martin, Ph.D.
Auburn University
“Pre-clinical gene therapy for GM2 in a feline model”
Miguel Esteves, Ph.D.
Massachusetts General Hospital
“AAV-mediated gene therapy for Tay-Sachs: Vector selection for pre-clinical development”
Aryan Namoodiri, Ph.D.
Uniformed Services University of the Heath Sciences
* “Conditional Gene Knockout of Acetyl Co A Synthease 1 to Mouse Canavan Disease and Other Leukodystrophies”
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This grant was made possible by through the generous support of NTSAD Members with children affected by Canavan and the Research Initiative Fund. *This project was recently awarded significant funding in a multi-year NIH grant – congratulations! |