The Rockefeller University

Neurologix, Inc.

Other

Medtronic, Inc.

Cornell University

Thomas Jefferson University

Neurologix Research, Inc.

Rudolf Magnus Institute

Michael G Kaplitt

Matthew J During

Andres M Lozano

Martin J Kaplitt

Joost Verhaagen

Sergei Moussatov

Brian L Alexander

Serguei Moussatov

Edward B Diethrich

The invention provides materials and methods for p11-mediated therapy of psychiatric disorders. The invention provides vectors for increasing p11 expression and methods of treating a mammal with one or more symptoms of a psychiatric disorder. The invention also provides methods for improving a mammal's responsiveness to treatment for a psychiatric disorder. The invention further provides model animals for depression and depression therapy.

Materials and methods for gene mediated therapy of psychiatric disorders

A fluid infusion device and a method of using the same. The device includes an outer, flexible guide catheter having a distal end for introduction beneath the skull of a patient and a proximal end remaining external of the patient. A flexible infusion fiber is located within the guide catheter and has a distal end extending outwardly from the guide catheter to be located in a target area within the patient's brain. The infusion fiber can be fixed or axially movable within the guide catheter. In the latter embodiment, the proximal end of the infusion fiber extending outwardly from the guide catheter can be manipulated to locate the distal end of the infusion fiber in the target area. An infusion pump is connected to the proximal end of the infusion fiber to infuse a minute quantity of fluid at an extremely low flow rate into the brain of the patient.

Infusion device and method for infusing material into the brain of a patient

Sequences are provided that are capable of directing circular adeno-associated virus replication, useful in vectors for providing therapeutic agents to a subject in need thereof. The vectors of the invention are particularly useful in the treatment of acute medical conditions requiring rapid gene expression. Further provided are methods for producing packaged defective viral vectors.

Method for generating replication defective viral vectors that are helper free

The present invention describes a method of identifying inducible genetic regulatory sequences that can control the transcription of specific gene transcripts. Methods of using inducible genetic regulatory sequences are also discussed. In particular, the genetic regulatory sequences of the present invention can modulate the transcription of a nucleic acid transcript in vivo.

Transcriptional regulation of target genes

The invention provides methods and compositions for localized delivery of a vector comprising a therapeutic agent to a specific region of the brain associated with a neurodegenerative diseases that is characterized by an excess buildup of buildup of intracellular protein aggregates. In particular, the invention provides methods and compositions used to deliver an adeno-associated virus vector (AAV) comprising a nucleotide sequence encoding an inhibitor of apoptosis protein (IAP) to cells in the region.

Use of apotosis inhibiting compounds in degenerative neurological disorders

The invention provide methods and compositions for localized delivery of a vector comprising a therapeutic agent to a specific region of the brain that is overstimulated in neurodegenerative diseases. In particular, the invention provides methods and compositions used to deliver an adeno-associated virus vector (AAV) comprising a nucleotide sequence encoding glutamic acid decarboxylase (GAD) to cells in the hippocampus, subthalamic nucleus of the basal ganglia, mesaphilia and thalamus.

Glutamic acid decarboxylase (GAD) based delivery system

Glutamic acid decarboxylase (GAD) based delivery systems

The invention provide methods and compositions for localized delivery of a vector comprising a therapeutic agent to a specific region of the brain that is overstimulated in neurodegenerative diseases. In particular, the invention provides methods and compositions used to deliver an adeno-associated virus vector (AAV) comprising a nucleotide sequence encoding glutamic acid decarboxylase (GAD) to cells in the subthalmic nucleus of the basal ganglia, mesaphilia and thalamus.

The invention provide methods and compositions for localized delivery of a vector comprising a therapeutic agent to a specific region of the brain that is overstimulated in neurodegenerative diseases. In particular, the invention provides methods and compositions used to deliver an adeno-associated virus vector (AAV) comprising a nucleotide sequence encoding glutamic acid decarboxylase (GAD) to cells in the subthalmic nucleus of the basal ganglia, mesaphilia and thalmus.

The invention relates to a method of delivering exogenous DNA to a target cell of the mammalian central nervous system using an adeno-associated virus (AAV)-derived vector. Also included in the invention are the AAV-derived vectors containing exogenous DNA which encodes a protein or proteins which prevent or treat nervous system disease, and a method of prevent or treating such disease.

AAV-mediated delivery of DNA to cells of the nervous system

The invention relates to a method of delivering exogenous DNA to a target cell of the mammalian central nervous system using an adeno-associated virus (AAV)-derived vector. Also included in the invention are the AAV-derived vectors containing exogenous DNA which encodes a protein or proteins which treat nervous system disease, and a method of treating such disease.

The invention relates to the use of adeno-associated virus vectors for the transfer of genes to the heart and vasculature. The vector preferably contains a gene encoding a protein which improves heart and vascular function during heart failure. In a specific embodiment, the vector is introduced into the heart and vasculature via a catheter, with the aid of fluoroscopy. The method and vectors for use therein provide for safe and stable gene expression of the transferred genes.

Method for transferring genes to the heart using AAV vectors

The present invention relates to a viral vector capable of the transfer and in vivo expression of growth-associated protein (B-50/GAP-43) in neuronal target cells of a mammalian host. The viral vector contains a recombinant DNA molecule comprising a B-50/GAP-43 gene operably associated with a promoter, which promoter controls short term, high level expression of the B-50/GAP-43 gene. Preferably, the viral vector is a defective viral vector, in particular a defective herpes virus or an adeno-associated virus. In a specific embodiment, defective herpesvirus, adenovirus, and adeno-associated virus viral vectors containing the rat B-50/GAP-43 gene under control of the human cytomegalovirus immediate early promoter have been prepared. The invention further provides a method for treating nerve damage in a subject. The method comprises introducing a vector comprising a B-50/GAP-43 gene operably associated with a promoter into a damaged nerve tissue of a subject. Preferably, the promoter controls short term, high level expression of the B-50/GAP-43 gene, such that the B-50/GAP-43 gene is expressed in the tissue of the subject. Preferably, the vector used in the therapeutic methods of the invention is a viral vector. The vectors of the invention, capable of expression a B-50/GAP-43 gene, can also be used in vitro to enhance the survival of cultured cells, in particular, cultured neurons for transplantation.

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New York, NY, United States of America

Michael G Kaplitt