Research Home University of North Carolina - Chapel Hill, Dr. Joseph Muenzer Gene therapy research on Sanfilippo B Syndrome (MPS III B) directed by Dr. Joseph Muenzer has been made possible at the University of North Carolina at Chapel Hill (UNC) by the support of The Children’s Medical Research Foundation, Inc. The goal of the MPS III B research at UNC is to develop methods using gene therapy to express or produce the enzyme missing (N-acetylglucosaminidase and abbreviated NaGlu) in MPS III B in the central nervous system. If the enzyme is made in adequate amounts and in the correct form, the storage of glycosaminoglycan (GAG) could be reversed or prevented from further occurring. This MPS III B gene therapy research at UNC has been possible because of a MPS III B animal model developed and provided to UNC by Dr. Elizabeth Neufeld and co-workers at UCLA. Dr. Muenzer’s laboratory has focused on using the adeno-associated viral (AAV) vectors as the method to deliver the human NaGlu gene into the brain of MPS III B animals. AAV vectors containing the coding sequence for the NaGlu gene have been made. Dr. Muenzer’s laboratory has successfully produced the NaGlu enzyme using AAV gene therapy and corrected the GAG storage in vitro in MPS III B human fibroblasts. The NaGlu enzyme has also been expressed using AAV gene therapy in many brain areas of MPS III B animals. Studies are in progress to determine how best to produce the NaGlu enzyme in the central nervous system and to determine if the expressed NaGlu enzyme in the MPS III B animals is able to correct GAG storage. The storage of GAG in cells and tissues is due to the missing enzyme NaGlu which causes the clinical problems seen in children with MPS III B. Although, we have not succeeded in proving that the enzyme produced after the injection of AAV vectors into the brain of animals corrects the GAG storage, studies with primary mouse brain cell cultures are very encouraging. We have been able to establish primary cultures of MPS III B mouse brain, kidney, liver and skin fibroblast cells. The AAV gene therapy vectors, when added to the cell cultures, are capable of producing the NaGlu enzyme in these MPS III B primary cell cultures, including brain cell, and the storage of GAG is corrected. In addition, AAV expressed enzyme is secreted by the cultured brain cells into the culture media. This secreted enzyme is also able to correct the storage of GAG when added to MPS III B mouse brain cells in culture. These experiments support the concept that AAV vectors can deliver the MPS III B human gene to brain cells, and the enzyme produced will correct the storage of GAG in the central nervous system. The MPS III B research at the University of North Carolina in Dr. Muenzer’s laboratory has been performed by Dr. Haiyan Fu in collaboration with Dr. Jude Samuski (Director, UNC Gene Therapy Center). The goal of Dr. Muenzer’s laboratory is to develop the preclinical animal data demonstrating successful enzyme production and correction of storage in MPS III B prior to applying to the Food and Drug Administration for permission to submit a Phase I AAV gene therapy clinical trial for Sanfilippo B Syndrome.