Research

Mucolipidosis Research - Grant Awarded

ISMRD is delighted to announce on behalf of all our funding partners in the ML Research initiative, the approval of a second proposal to begin research on Osteoporosis in Mucolipidosis II - A Potential Corrective approach.

Dr Sandra Pohl works in the  section of Biochemistry, Children's Hospital, University Medical Centre Hamburg-Eppendorf, Germany. Her work will look at how I1-6 may represent a potential target for the treatment of osteoporosis in ML II and ML III.

The aim of the project is: Skeletal alterations are common symptoms in mucolipidosis (ML) II and III patients leading to progressive decline of mobility, stiffness and chronic joint pain, strongly reducing the quality of life. In bone cells of patients the targeting of multiple lysosomal enzymes is disturbed. Consequently, the accumulation of nondegraded storage material in lysosomes impairs the function of bone-forming osteoblasts, osteocytes and chondrocytes of the cartilage. We found that the progressive bone loss in MLII mice is caused by the presence of dysfunctional osteoblasts combined with an increased number of bone-resorbing osteoclasts, which is most likely induced by the strongly elevated expression of the osteoclastogenic cytokine interleukin-6 (Il-6), that could be shown also in MLIII cultured osteoblasts. Therefore,cytokine interleukin (IL-6) may represent a potential target for treatment of osteoporosis in MLII and MLIII to restore correct bone remodeling in patients. The applied experimental in-vivo approach to block Il-6-mediated increase in osteoclast number in MLII and MLIII represents an urgent first step therapeutic strategy, which can profit from the concomitant phase II clinical studies using an Il-6 signaling inhibitor.

ISMRD is thrilled with the tremendous support from so many families and groups towards this outcome, and delighted to be supporting this significant new development in research into this serious disease.

ISMRD logo1 MPS USA MPS Australia MPS Spain

The Wagner Foundation, The Irish MPS Society,

The Austrian MPS Society, Rock4Dakotah


ISMRD is delighted to announce on behalf of all our funding partners in the ML Research initiative, the approval of a proposal to begin research on Gene Therapy in ML II.

Allison Bradbury and Charles Vite from the University of Pennsylvania will work with Steven Gray who is based at the University of North Carolina. Their research project will explore the delivery of a healthy copy of the defective gene using a viral delivery system. The ML II cats at the University of Pennsylvania have been the basis for important study of this disease for many years now.

ISMRD launched this ML research initiative early in 2016 and has drawn in vital funding partnerships from the US National MPS Society, the Wagner Foundation, the Spanish MPS Society, Rock4Dakotah, the Australian MPS Society, the Austrian MPS Society, the Irish MPS Society, and many families from around the globe who worked so hard to fundraise for this initiative. Together we raised a stunning $150,000 which has enabled this research to begin.

The formal title of the project is: To evaluate AAV Gene Therapy in the feline model of ML II.

The aims of the project are: Feline mucolipidosis II (ML II) is a model of human ML II, a devastating and incurable disorder that is often fatal in childhood. ML II is an inherited disorder in which one copy of a faulty gene is inherited from each parent. Gene therapy utilizes a virus as a vehicle to deliver a healthy, functional copy of the defective gene.

One specific type of virus, adeno-associated virus (AAV), has been engineered to act as a safe and efficient gene delivery system. Systemic, or intravenous, delivery of AAV has been evaluated in animal models of numerous diseases related to ML II and has recently been approved for a human clinical trial.

In light of recent success in animal models and human patients of similar diseases, we are encouraged that systemic AAV gene therapy holds potential as a treatment for ML II. In this study we will evaluate intravenous AAV gene therapy in the feline model of ML II in order to collect preclinical data to inform human clinical trials.

ISMRD is thrilled with the tremendous support from so many families and groups towards this outcome, and delighted to be supporting this significant new development in research into this serious disease.