Research is Underway

The following 3 grants were awarded for 2017. Research updates will be posted when available.

1. Proof of concept study of HSC gene therapy for Tay-Sachs disease
   Alessandra Biffi, MD
   The project will test a novel gene therapy approach for Tay-Sachs and Sandhoff Disease by establishing a stable population of brain cells, which will serve as a sustained and balanced supply of the deficient enzymes in the patients.
2. Minimally invasive delivery of AAV gene therapy in the Tay-Sachs Sheep
   Heather Gray-Edwards
   The study will evaluate the efficacy and biodistribution of the state-of-the-art gene therapy in Tay-Sachs Disease sheep.
3. Development of a quantitative method for the determination of a pentasaccharide in GM1-gangliosidosis patient cells to assess the potential therapeutic efficacy of a beta-galactosidase pharmacological chaperone drug candidate
   Tim Wood / Stephane Demotz
   This study's goals are to develop a quantitative, sensitive, and robust method to determine a biomarker for GM1-gangliosidosis, and to explore treatment conditions of a drug candidate for GM1 patient cells.

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Research is Underway

1. Rapid Identification of New Biomarkers for the Classification of GM1 and GM2 Gangliosidoses: A HNMR-linked Metabolomics Stragegy
   Martin Grootveld
   By identifying the markers of GM1 and GM2 in plasma, cerebrospinal fluid, and urine, a greater understanding of the disease will contribute to identification of treatments.
2. Novel Combined Gene/Cell Therapy Strategies to Provide Full Rescue of the Sandhoff Pathological Phenotype
   Angela Gritti
   This study will evaluate Sandhoff Disease gene and cell therapy approaches, comparing three therapeutic methods to assess these therapies for Sandhoff disease.
3. Clinically Relevant Outcome Measures for Patients with Late Onset Tay-Sachs disease
   Ascertained Real-Time Through Patient Wearable Technology
   Cynthia Tifft
   This study will collect patient data to identify outcome measures for future clinical trials for Late Onset Tay-Sachs.
4. Identifying Novel Therapeutics for Treating GM2 Gangliosidoses
   Beverly Davidson
   This study will analyze the drugs Miglustat and Lucerastat, and drugs that act in a similar manner, testing their ability to be used as a treatment for GM2.

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Research is Underway

1. Development and validation of a rapid, MS/MS-based method
   to detect Hexosaminidase deficiency in Tay-Sachs disease
   Denis Lehotay
   Advancing research for Tay-Sachs screening, this study furthers the work to establish newborn screening and an eventual cure.
2. Intravascular Gene Therapy Studies to Improve Methods of Delivery
   Douglas Martin
   This research advances work into developing a less invasive and safer approach to treating Tay-Sachs and Sandhoff Disease.
3. Defining the Natural History of Canavan Disease through Development of an International Registry
   Healther Lau / Paola Leone
   
An international registry of Canavan Disease will contribute to showing the effectiveness of potential therapies and provide more data for future studies.
4. Registry and Repository for Late Onset GM2 Gangliosidoses
   Florian Eichler
   This study will take steps to accumulate and organize information, leading to improved trial design for Late Onset GM2 patients. It includes review of literature and surveys, determination of optimal outcome measures for a pilot project, and creation of electronic case report forms.
5. Generation of a knock-in mutant Hexb Mouse Model
   Eric Sjoberg
   Advancing Late Onset research, this study will focus on creating a model environment equivalent to a human Late Onset condition. The model will be made available for other Late Onset research.

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Research Completed

Lectin-Assisted Transnasal Delivery of Corrective Enzyme for GM1 Gangliosidosis

This grant funded research into Transnasal delivery, exploring this alternative as a method of delivering enzyme replacement therapy. With its distinctive advantage of being convenient and non-invasive, Transnasal delivery offers potential for treating brain disorders like GM1.

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Research Completed

Studies of the Molecular and Biochemical Bases of Neurodegeneration in Sialidosis
NEU1 is a key lysosomal enzyme in brain cells. Patients with Sialidosis, a rare pediatric lysosomal storage disease, have too little or no NEU1 enzyme. Scientists from d’Azzo Lab analyzed the effects of NEU1 deficiency and identified new genes that may help develop therapies for both Sialidosis and Alzheimer's disease. Read More

Research Completed

1. Clinical Outcome Measures for a Gene Therapy Trial in Infantile and Juvenile GM2
   Florian Eichler
   Neurological and neuropsychological evaluations of children with GM2 resulted in a Severity Scale that will help scientists further clinical trial design for GM2 gene therapy.
2. Optimization of Efficacious Gene Therapy for Canavan Disease
   Guangping Gao
   Advancing gene therapy for Canavan disease, this research examined the efficiency of deliverying therapy by injections to the central nervous system. Both systematic intravenous (IV) injections and direct-to-brain intracerebroventricular (ICV) injections were studied.
3. Studies of Taurine-Conjugated GM2 in Tay - Sachs Disease
   Yu-Tah Li
   This study explored lipids in the brain of Tay-Sachs patients.

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Research Completed

1. The Therapeutic Potential of Human Induced Pluripotent Stem Cells (IPSCs)
   in the Sandhoff Disease Mouse Model of Lysosomal Storage Disorders
   Jean-Pyo Lee
   Advancing development of stem them therapy for Tay-Sachs and Sandhoff disease, this pilot study examined the benefits of using transplanted stem cells with a protein factor.
2. Developing a High Throughput Screening Assay to Identify Potential Drugs for Metachromatic Leukodystrophy
   Gustavo Maegawa
   Researchers developed expertise to convert skin cells to brain cells, to be used as a model system to test potential drugs for neurological diseases.
3. Sheep as a Model of Tay-Sachs Disease
   Doug Martin
   This research characterizes the disease progression of Tay-Sachs to assist with therapeutic strategies.
4. Optimizing the Therapeutic Potential of Anti-inflammatory Therapy in
   Tay-Sachs and Related Diseases: Targeting IL-β Generated by Aberrant NLRP3 Inflammasome Activation
   Fran Platt
   The impact of inflammation on the symptoms of lysosomal storage diseases was researched to further potential therapies in treating Tay-Sachs and Sadhoff diseases.
5. Development of an in vitro approach to identify molecular pathways of Canavan disease
   Maria Traka
   From this research into the rare leukodystrophy Canavan disease, it was determined the loss of key enzyme ASPA function did not lead to the death of oligodendrocyctes neuron cells. This study ay help identify new pathways for treating Canavan disease.

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Research Completed

1. Investigator-Initiated Clinical Trial of Pyrimethamine
   Joe Clarke & Edwin Kolodny
   This study examined the potential clinical benefit of a therapy called PYR (Pyrimethamine) for the treatment of late-onset Tay-Sachs Disease and Sandhoff Disease. Further studies are needed to evaluate the benefits and safety.
2. A Biomarker for Disease Progression in GM2 and Other Neurolipidoses
   Florian Eichler
   This research studied the use of Magnetic Resonance Imaging (MRI) techniques to examine cerebral blood flow changes, providing more data to detect diseases at an early stage.
3. Novel Therapy for Tay-Sachs Disease, Sialidosis and Ggalactosialidosis
   Using Metabolic Bypass Catalyzed by the Lysosomal Sialidase Neu4
   Alexey Pshezhetsky
   This research provided an explanation as to why the Tay-Sachs disease is severe in humans, but not in mice up to one year of age. The results contribute to further study of the treatments for Tay-Sach disease.
4. Combination Therapy for Krabbe Disease
   Mark Sands
   This study combined Bone Marrow Transplantation (BMT) with gene therapy for the treatment of Globoid-cell leukodystrophy (GLD, Krabbe disease), proposing this viabile and less invasive way to treat the disease.

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On this page:

Research Initiative Grants
2008
2007
2004-2005
2003
2002

2008 Research Initiative Grants

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”

2008 Research Grants - Resulting Publications

Gentner, S, et al., Therapy of Globoid Cell Leukodystrophy Sci Transl Med 2, 58ra84 (2010)

Kyrkanides, S, et al., The trigeminal retrograde transfer pathway in the treatment of Neurodegeneration, Journal of Neuroimmunology, 209 (2009) 139–142 pdf Journal of Neuroimmunology Pathway Treatment Neuro Kyrkanides 2009 (1.08 MB) (.pdf)

2007 Research Initiative Grants

Susan L. Cotman, PhD
Massachusetts General Hospital
“Small molecule screening to identify modifiers of lysosomal trafficking, a putative therapy for Batten”

Doug Martin, PhD
Auburn University
“Pre-clinical gene therapy for GM2 in a feline model”

Miguel Esteves, PhD
Massachusetts General Hospital
“AAV-mediated gene therapy for Tay-Sachs: Vector selection for pre-clinical development”

Aryan Namoodiri, PhD
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

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