Lysosomal Storage Diseases Research Consortium

In 2005-2006 (to date), NTSAD opted to focus its research funding efforts on the Lysosomal Storage Disease Research Consortium (LSDRC) grants initiative. Co-founded by NTSAD and the National MPS Society, the LSDRC is a collaborative research-funding group comprising LSD patient support groups and private family research foundations. The LSDRC has entered into an agreement with the National Institute of Neurological Disorders and Stroke (NINDS) for the purpose of a jointly sponsored program to provide financial, scientific and administrative support towards preclinical or translational research specifically addressing the neurological aspects of lysosomal storage disorders (LSD). The NINDS and LSDRC administrate their own funded applications and each entity is responsible for monitoring scientific progress that each entity supports through this initiative.

The goal of this mechanism is to stimulate interest in and to solicit applications for lysosomal storage disorder research focused on improving central nervous system (CNS) treatment outcomes, enhancing the effectiveness of delivery and targeting of cells, enzymes, drugs and genes into the brain. This funding opportunity specifically encourages the transition from basic studies in LSDs to translational research for improved delivery of therapeutic cells, proteins, genes and small molecules across the blood-brain barrier.

The lysosomal storage diseases are a group of about 50 different diseases, each characterized by a specific lysosomal enzyme deficiency in a variety of tissues. They occur in total in approximately 1 in 5,000 live births and display considerable clinical and biochemical heterogeneity. The majority are inherited as autosomal recessive conditions although two, MPS II and Fabry disease, are X-linked.

Lysosomal enzymes are normally involved in the intracellular degradation of macromolecules to low molecular weight compounds. Deficiencies of these enzymes result in the accumulation of un-degraded macromolecules within the lysosomes. As a result the cells do not perform properly leading to progressive damage throughout the body, including the heart, bones, joints, respiratory system and central nervous system.

There is no cure for these disorders. Enzyme replacement therapy is a treatment that can benefit the somatic manifestations of LSDs, but when given by intravenous infusion does not enter the brain. The neurological progression continues in those LSDs with associated CNS involvement.

LSDRC/NINDS Partnership

The National Institute of Neurological Disorders and Stroke at NIH and the LSDRC partnership encourages and supports research. Each member of the partnership has responsibility for conducting independent peer review of the research funding applications that are received in response to the Program Announcement. The NINDS makes funding decisions on applications adhering to the standard NIH receipt, review and award dates and thereafter for the three-year duration that the announcement is active. If, following decisions for each NINDS funding cycle, there remain some unfunded high-quality grant applications, the NINDS shares those applications and summary statements with the LSDRC for consideration for funding. The LSDRC makes an independent decision to fund these applications and provides funds directly to investigators.

The NINDS and the LSDRC administrate their own funded applications and each entity is responsible for monitoring scientific progress. As appropriate, the principal investigators may be asked to share the NINDS progress reports with the LSDRC representatives, and vice versa.
It can be viewed at: http://grants.nih.gov/grants/guide/pa-files/PAS-06-202.html.

NEXT EXPIRATION DATE for R01 Applications: November 7, 2007

LSDRC Application Review Committee

• Dr. Mark Haskins (chair), University of Pennsylvania, Veterinary Pathology
• Dr. Lorne Clarke, British Columbia Children’s Hospital, Department of Medical Genetics
• Dr. Alessandra D’Azzo, St. Jude Children’s Research Hospital, Department of Genetics
• Dr. Robert Desnick, Mount Sinai School of Medicine, Department of Human Genetics
• Dr. Jeffrey Medin, University of Toronto, Department of Medical Biophysics
• Dr. Mark Sands, Washington University School of Medicine, Division of Bone Marrow Transplantation and Stem Cell Biology
• Dr. William Sly, St. Louis University Medical School, Department of Biochemistry and Molecular Biology
• Dr. Steven Walkley, Albert Einstein College of Medicine, Sidney Weiner Laboratory of Genetic Neurological Disease

The LSDRC Review Committee reviews all applications and related materials received from the NINDS, including summary statements, and makes funding decisions based on the amount of resources available as determined by the LSDRC Executive Committee. Several different grants have been funded through this partnership.

From its current funds, the LSDRC Review Committee may give priority to applications needing additional targeted research. Innovative science and novel therapeutic approaches are of interest to the LSDRC. The goal is that results from the targeted research will enhance the principal investigator’s opportunity of receiving NIH funding. The total amount awarded depends on the quality of the applications received and the areas of need. NIH study section reviews and scores supplement the reviews of the LSDRC Review Committee, however, please note that decisions with respect to LSDRC funding will be made independent of the NIH scores and summary statement content.

LSDRC Consortium partners

• The National MPS Society, Inc.
• National Tay-Sachs & Allied Diseases Association, Inc.
• The Canadian Society for Mucopolysaccharide & Related Diseases, Inc.
• The Sanfilippo Syndrome Medical Research Foundation, Inc.
• Hunter’s Hope Foundation
• National Niemann-Pick Disease Foundation

2006-2007 LSDRC Grantees and Institutions

Eain M. Cornford, PhD
Brentwood Biomedical Research Institute
"Gene delivery across the blood-brain barrier in Lafora knockout mice project”

Christina Schroeder, Ph.D.
The Scripps Research Institute
“CNS Therapy Development for Lysosomal Storage Disorders”

Kostantin Dobrenis, Ph.D.
Albert Einstein College of Medicine of Yeshiva University
“Gangliosidosis Therapy Using Neuronotropic Enzyme”

Angela Gritti, Ph.D.
Fondazione Centro San Raffaele del Monte Tabor - DIBIT
“Neural Stem Cell-based Therapy for GM2 Gangliosidosis”

Synthia Mellon, Ph.D.
University of California, San Francisco
“Neurosteroid Therapy for Lysosomal Storage Disorders”

Thomas N. Seyfried, MS, Ph.D.
Boston College
“Evaluate MJ-DGJ as a substrate reduction therapy, neural stem cells (NSCs) as a cross-correctional therapy, and caloric restriction (CR) as an anti-inflammatory therapy for ganglioside storage diseases”