Recombinant adeno-associated virus for the treatment of GRN-associated adult-onset neurodegeneration

摘要

Provided is a recombinant AAV (rAAV) suitable for use in treating adult onset neurodegeneration caused by granulin (GRN) hemiinsufficiency, such as progranulin (PGRN)-associated frontotemporal dementia (FTD). rAAV comprises (a) an adeno-associated virus 1 capsid, and (b) a vector genome packaged in an AAV capsid, said vector genome comprising an AAV inverted terminal repeat, a coding sequence for human progranulin, and progranulin control sequences that direct the expression of Also provided is a method of treating a human patient with PGRN-FTD and other adult-onset neurodegeneration caused by granulin (GRN) insufficiency, comprising a recombinant adeno-associated virus having an adeno-associated virus 1 (AAV1) capsid. (rAAV) to the central nervous system (CNS), wherein the rAAV further comprises a vector genome packaged in an AAV capsid, wherein the vector genome is an AAV inverted terminal repeat, encoding for human progranulin sequences, and regulatory sequences that direct expression of progranulin.