Prevail Therapeutics, Inc.

Columbia University

Alector LLC

Asa Abeliovich

Herve Rhinn

Laura Heckman

Franz Hefti

Li Chin Wong

Hsuan-Ni Lin

Arnon Rosenthal

Tina Schwabe

Seung-Joo Lee

Ilaria Tassi

Toru Yamashita

Hervé Rhinn

GENE THERAPIES FOR LYSOSOMAL DISORDERS

This Application is a continuation of international patent application serial number PCT/US2018/054223, filed Oct. 3, 2018, which claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application Ser. No. 62/567,303, filed Oct. 3, 2017, entitled 'GENE THERAPIES FOR LYSOSOMAL DISORDERS', and 62/567,305, filed Oct. 3, 2017, entitled “GENE THERAPIES FOR LYSOSOMAL DISORDERS”, the entire contents of each of which are incorporated herein by reference.

Gene therapy for neurodegenerative disorders

The disclosure relates to compositions and methods for treatment of diseases associated with aberrant lysosomal function, such as fronto-temporal dementia (FTD). The disclosure also provides expression constructs comprising a transgene encoding progranulin or a portion thereof. The disclosure provides methods of treating FTD by administering such expression constructs to a subject in need thereof.

Gene therapies for lysosomal disorders

The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof alone or in combination with one or more PD-associated genes. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

The disclosure relates to compositions and methods for treatment of diseases associated with aberrant lysosomal function, such as Parkinson's disease and Gaucher disease. The disclosure provides expression constructs comprising a transgene encoding beta-glucocerebrosidase, an inhibitory RNA targeting alpha-Synuclein, or a combination of the foregoing. The disclosure further provides methods of treating Gaucher disease, Parkinson's disease or other synucleinopathies by administering such expression constructs to a subject in need thereof.

The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding one or more inhibitory nucleic acids targeting SCNA or a portion thereof, TMEM106B or a portion thereof, or any combination of the foregoing. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof, Lysosomal Membrane Protein 2 (LIMP2), Prosaposin, or any combination of the foregoing. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

Provided herein are transgenic non-human animals whose genomes comprise two or more human genes selected from TREM1, TREML1, TREM2, TREML2, and TREML4, to methods of screening candidate agents that bind to and/or modulate the function and/or activity of at least one of the human genes in the transgenic non-human animals, and to methods of screening candidate agents to determine their effect on one or more activities and/or functions associated with expression of at least one of the human genes in the transgenic non-human animals. Further provided herein are methods of recapitulating a human TREM immune system in a non-human animal, and methods of generating a non-human animal disease model comprising a human TREM repertoire.

Transgenic mice expressing human TREM proteins and methods of use thereof

The invention provides optimized miRNA sequences and their therapeutic use. The invention provides optimized miRNA constructs for treatment of neurodegenerative diseases.

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New York, NY, United States of America

Asa Abeliovich