2006 Grants Funded

The LSD Research Consortium (LSDRC) is a collaborative research-funding group, comprised of 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 will administrate their own funded applications and each entity will be 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 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.

Relationship Between the LSDRC and the NINDS

The NINDS will have sole responsibility for conducting peer review of the applications that are received in response to the Program Announcement. It can be viewed at http://grants.nih.gov/grants/guide/pa-files/PAS-04-120.html. The NINDS plans to make funding decisions on applications adhering to the standard NIH receipt, review and award dates starting February 2005 and thereafter for the 3-year duration that the announcement is active. If, following decisions for each NINDS funding cycle, there remain some unfunded high-quality applications, the NINDS will share those applications and summary statements with the LSDRC for funding consideration. The LSDRC will make independent decisions to fund these applications and will provide funds directly to investigators.

The NINDS and the LSDRC will administrate their own funded applications and each entity will be responsible for monitoring scientific progress that each entity supports through this initiative. As appropriate, the principal investigators may be asked to share the NINDS progress reports with the LSDRC representatives, and vice versa.

Application Review Committee and Funding Decisions

Drs. Elizabeth Neufeld and Alessandra D’Azzo reviewed the list of scientific and medical advisors from the 6 participating parent support groups to establish an independent grant review committee. The members of the LSDRC Grant Review Committee are:

• 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 will review all applications and related material received from the NINDS, including summery statements and make funding decisions based on the amount of funds available for research funding as determined by the LSDRC Executive Committee. Several different grants may be funded.

The LSDRC currently has $310,000 to award for the duration of the program, although this amount may increase as other groups join the LSDRC or funding is otherwise enhanced. TheLSDRC 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 then receiving NIH funding. The total amount awarded will depend on the quality of the applications received and the areas of need. NIH study section reviews and scores will supplement the reviews of the LSDRC committee, however, please note that decisions with respect to LSDRC funding will be made independent of the NIH scores and summary statement content.

Eligible Research Costs

Grant applications may fund salaries, equipment essential to the project, and specified consumable supplies. Grant monies are not to be used to cover general overhead of the institution involved.

The lysosomal storage diseases are a group of about 40 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 undegraded 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.

For information about LSDs http://www.lsdn.com/glance_overview.htm