The National MPS Society awarded $547,000 in grant funding for 2012 which includes the second year funding for grants awarded in 2011 plus the 2012 grants. The funding the Society provides has been and continues to be critical as we move forward with our mission to find the cures. We received 16 letters of intent from researchers around the world for the three grants offered in 2012. After reviewing those letters, our Scientific Advisory Board review committee requested full grant proposals from seven researchers.
The Society will also fund $25,000 to support the Lysosomal Disease Network’s NIH grant research goals. The funding is designed for the Neuroimaging Core, which will benefit the four MPS projects. An additional $15,000 has been allocated for a mucolipidosis partnership grant with the Gandhi Foundation to Dr. Sara Cathey at Greenwood Genetics Center, “PTC 124 for nonsense mutation suppression in ML II and III cultured fibroblasts.” A $10,000 partnership grant with the Ryan Foundation funded the University of MN project “Brain Structure and Function in Developmentally Normal Children Ages 4-7.” The Society also provides funding for post-doctoral fellows to attend scientific meetings, such as the American Society of Gene and Cell Therapy.
MPS II – two years @ $45,000 each year
Gustavo H.B. Maegawa, MD, PhD
Johns Hopkins School of Medicine, Department of Pediatrics
“Induced-neuronal (iN) cells as tools to study the pathogenesis of neurological manifestations in MPS-II.”
Mucopolysaccharidosis type II (MPS-II) is a genetic disease caused by the inability to breakdown large molecules called glycosaminoglycans. MPS-II is caused by the deficiency of an enzyme located in the lysosome, essential recycling units present in each cell. In MPS-II, the accumulation of undegraded material results in dysfunction of the lysosomes, compromising the entire cells and ultimately multiple organs/systems. The mechanisms how the storage of glycosaminoglycans can severely affect brain causing severe mental disabilities have not been fully elucidated. Using a new technology, we are now able to convert skin cells into
brain cells, called “induced-neuronal cells”. The hypothesis of the project is that the induced-neuronal cells from patients are research tools to study mechanisms causing the neurological problems in MPSII. In this project, I aim to convert skin cells from MPS-II patients into the induced-neuronal cells and determine how they can be used to study brain disease in MPS-II. The results of this project will provide cell-model to study the brain disease in the MPS-II, which can subsequently result in the discovery of novel treatments for the neurological problems commonly seen in affected patients.
MPS IV – two year @ $40,000 each year
Shunji Tomatsu, MD, PhD
Nemours Children’s Clinic – Delaware Valley of the Nemours Foundation
“Development of Long Circulating Enzyme Replacement Therapy for MPS IVA.”
Mucopolysaccharidosis type IVA (MPS IVA) results from a deficiency of the enzyme N-acetylgalactoseamine- 6-sulfate sulfatase. This enzyme is required for the breakdown of complex sugars called “glycosaminoglycans (GAGs).” GAGs are normally found throughout the body, including bones and joints, and are constantly broken down and replaced with new GAGs. In MPS IVA, GAGs cannot be broken down properly, resulting in their abnormal accumulation. Patients with MPS IVA often present with systemic skeletal abnormalities (bone deformities, short stature, and spinal cord compression).
Several treatment strategies for MPS have been tested. These treatments showed limited effect on bone and brain involvement. Recently, an enzyme replacement therapy strategy using modified long-circulating β- glucuronidase on MPS VII mice was shown to almost completely correct brain storage of GAGs and to reduce storage materials substantially in bone. Given the success of this therapy in MPS VII mice, the question of whether the modified enzyme also works to improve bone pathology is of great interest in MPS IVA mice. We have developed an assessment method to evaluate skeletal pathology quantitatively in MPS mice. We expect the new treatment strategy to improve bone lesions in MPS IVA, leading to increased mobility and a better quality of life
MPS III Grand Challenge Grant – multi year $235,000 with support from Team Sanfilippo
Dr. Brian Bigger
Stem Cell & Neurotherapies Group
“Evaluation of high dose genistein aglycone in the treatment of mucopolysaccharide disease
types IIIA, B and C.”