Research Ben's Dream has provided funding grants for the following research activities: Columbus Children's Research Institute - Ohio State University, Dr. Haiyan Fu University of North Carolina – Chapel Hill, Dr. Haiyan Fu In addition our collaborative fundraising efforts with the Children's Medical Research Foundation (CMRF) has helped provide funding for grants CMRF has issued to the following principle investigators at University or Hospital research centers: University of California – Los Angeles, Dr. Elizabeth Neufeld University of North Carolina – Chapel Hill, Dr. Joseph Muenzer University of Minnesota, Dr. Chester Whitley Medical College of Georgia, Dr. Robert Yu University of South Florida, Dr. Paul Sanberg Michigan State University, Dr. Margaret Jones Women’s & Children’s Hospital – Australia, Dr. John Hopwood To date, researchers have successfully cloned the human gene and cDNA encoding of the enzyme missing in Sanfilippo patients, allowing them the potential of correcting the gene. They also have developed an automated method of sequencing the DNA (mutation analysis) of the Sanfilippo gene in afflicted patients. A Sanfilippo "B" mouse model was developed enabling further studies of the disease as well as advances in testing for potential therapies. These models have been shared with other investigators and are currently available to other interested institutions. Gene Therapy continues to progress. Researchers have constructed two adeno-associated viral (AAV) gene therapy vectors containing the missing gene in Sanfilippo patients. To date, results have demonstrated increased long term enzyme activity in specific areas of the Sanfilippo mouse brain that were microinjected with the vectors. In looking at the efficacy of the gene transfer, researchers are currently examining the spreading of the corrected gene throughout the brain and whether the expressed enzyme corrects the storage. The goal of this research is to develop basic and pre-clinical data needed to obtain FDA approval for a Sanfilippo AAV gene therapy clinical trial. Research on Enzyme Replacement Therapy (ERT) has been successful in reversing lesions in the liver, and investigators are currently working on different methods to ensure transfer of the enzyme into the brain. Once the blood-brain barrier is breached, it is expected that ERT will provide an effective therapy for Sanfilippo and other diseases causing brain dysfunction. Several commercially available drugs that are active as inhibitors of ganglioside production (known to contribute to the development of mental retardation) will be orally or intravenously administered to the Sanfilippo mouse model. Cell Replacement Therapy also will be tested as a treatment for Sanfilippo Syndrome by investigating the possibility of grafting normal glial cells (essential elements of the nervous system) into the brain of Sanfilippo mice. The hope is that the grafted normal glial cells can correct the metabolic defects in abnormal nerve cells in the mice. This strategy has been successfully applied to the treatment of a number of neuro-degenerative diseases, such as Multiple Sclerosis and Parkinson's Disease.