NTSAD Research Initiative

2010 Research Initiative Funded Researchers and Projects

In April, the NTSAD Research Initiative Committee announced 5 new grants totaling one-half million dollars for 2010. This is the largest dollar amount that has been funded in the Research Initiative’s history and is the first time that multi-year grants have been awarded: 4 of the 5 grants are two-year grants. The grants are as follows:

Jean-Pyo Lee, PhD / Evan Y. Snyder, MD, PhD (Burnham Medical Research Institute): The Therapeutic Potential of Human Induced Pluripotent Stem Cells (IPSCs) in the Sandhoff Disease Mouse Model of Lysosomal Storage Disorders.

  • Description: This cutting-edge project will investigate the mechanisms of a new type of stem cells: induced pluripotent stem (IPS) cells.
  • Benefit: If IPS derived cells could be used for therapy that would be a major step forward, as it takes away the problem of tissue rejection and the problem of working with embryonic stem cells.

Maria Traka, PhD (University of Chicago): Development of an in vitro approach to identify molecular pathways of Canavan disease

  • Description: The investigator will use a mouse model of Canavan disease to study the molecular pathways in Canavan disease.
  • Benefit: The project has a high likelihood of enhancing our knowledge of Canavan disease which will help develop therapies in the future.

Fran Platt, PhD (University of Oxford): Optimizing the Therapeutic Potential of Anti-inflammatory Therapy in Tay-Sachs and Related Diseases: Targeting IL-1ß Generated by Aberrant NLRP3 Inflammasome Activation

  • Description: Develop a mouse model of Sandhoff disease that lacks a particular receptor and use various analyses to determine the degree of anti-inflammatory benefit achieved in these mice, which will define the mechanism that triggers inflammation.
  • Benefit: This grant addresses a significant problem involving ganglioside-associated neuro-inflammation. Clinical trials could proceed quickly if confirmation of a particular inflammatory mechanism can be confirmed.

Gustavo Maegawa, PhD (Johns Hopkins University) Developing a High Throughput Screening Assay to Identify Potential Drugs for Metachromatic Leukodystrophy

  • Description: This grant is based on the principle that small molecules can enhance residual enzyme activity in patients with lysosomal storage diseases (LSD’s). Through high throughput screening, candidate compounds for metachromatic leukodystrophy will be identified.
  • Benefit: The cell-based assay will also indentify small molecules that could have broader application for treatment of other LSD’s.

Doug Martin, PhD (Auburn University): Sheep as a Model of Tay-Sachs Disease

  • Description: Characterization of disease progression in Tay-Sachs disease sheep and treatment the sheep with AAV vectors).
  • Benefit: The sheep is the first true Tay-Sachs disease animal model (as the mouse and cat models are Sandhoff disease models). Also, the large sheep brain is closer in size to the human brain. Therefore, the current proposal is an essential step to test promising therapeutic strategies.

 

2009 Research Initiative Funded Researchers and Projects

Florian Eichler, MD
Massachusetts General Hospital
A Biomarker for Disease Progression in GM2 and other Neurolipidoses

Alexey Pshezhetsky, PhD
University of Montreal
Novel Therapy for Tay-Sachs Disease, Sialidosis and Galactosialidosis using a Metabolic Bypass Catalyzed by the Lysosomal Sialidase Neu4

Mark Sands, PhD
Washington University Combination Therapy for Krabbe Disease; co-funded with Hunter’s Hope Foundation

Joe Clarke, MD, PhD
Hospital for Sick Kids Toronto
Pyrimethamine Clinical Trial for Late Onset Tay-Sachs

Edwin Kolodny, MD
New York University Medical Center
Pyrimethamine Clinical Trial for Late Onset Tay-Sachs

 

2008 Research Initiative Funded Researchers and Projects

Angela Gritti, PhD and Alessandra Biffi, PhD
San Raffaele Telethon Institute for Gene Therapy
“Evaluation of Combined Approaches Using Hematopoietic and Neural Stem Cells for the Treatment of Globoid Cell Leukodystrophy”

Stephanos Kyrkanides, PhD
Stony Brook University “Retrograde transfer of therapeutic vectors enabled by the trigeminal sensory system”

 

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
* “Preclinical Research toward Acetate Supplementation Therapy for Canavan Disease”

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!

 

2004-2005 Research Initiative Funded Researchers and Projects:

James A. Shayman, M.D.
University of Michigan
“High throughput screening for inhibitors of ganglioside GM2 synthase”

 

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).

Lee et all. Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease. Nature Medicine, March 2007. (click here for simplified summary)

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)”

* 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

Kasperzyk et al. N-butyldeoxygalactonojirimycin reduces neonatal brain ganglioside content in a mouse model of GM1 gangliosidosis. J. Neurochem. 89: 645-653, (2004). (click here for simplified summary)

Hauser et al. Inheritance of lysosomal acid beta-galactosidase activity and gangliosides in crosses of DBA/2J and knockout mice. Biochem. Genetics, 42: 241-257, (2004). (click here for simplified summary)

Baek et al. Poster Session DP2: Gangliosides: N-butyldeoxygalactonojirimycin reduces brain ganglioside and GM2 content in neonatal Sandhoff disease mice. J. Neurochem. 90: (Suppl. 1) 89, (2004).

Denny et al. Poser Session PSM06: Metabolism: Retinal glycosphingolipid abnormalities in Sandhoff and GM1 gangliosidosis mice. J. Neurochem. 94 (s1), 39-43. (2005).

Denny et al. Caloric restriction extends longevity without altering brain lipid composition or cytoplasmic neuronal vacuoles in Sandhoff mice. J. Neurochem. 94 (s1), 39-43. (2005). (click here for simplified summary)

Baek et al. Neural stem cell transplantation reduces brain GM2 and GA2 content in a mouse model of Sandhoff disease. J. Neurochem. 94 (s1), 23. (2005). (click here for simplified summary)

Baek et al. N-butyldeoxygalactonojirimycin reduces brain ganglioside and GM2 content in neonatal Sandhoff disease mice. J. Neurochem. 90: (Suppl. 1) 89, (2004). (click here for simplified summary)

Kyrkanides et al. B-hexosaminidase lentiviral vectors: transfer into the CNS via systemic administration Molecular Brain Research (2005) 133: 286-298. (Click here for simplified summary)