The present invention relates to lysosomal enzymes modified by use of cell based methods, a compositions comprising a modified lysosomal enzyme, as well as methods for producing a modified lysosomal enzyme and therapeutic use of such modified lysosomal enzyme. In particular, the present disclosure relates to a modified lysosomal enzyme which has low Man6P and low exposed Mannose and high sialic acid content of alpha2,3 type enabling long circulation time and improved uptake into difficult-to-reach organs like heart, kidney and brain.

Disclosed are compositions and methods of treating a neurodegenerative disease in an individual. The methods disclose administration of an Integrin α4β1, Very Late Antigen-4 positive neural precursor cell (“VLA4+NPC”) transfected with a lentivirus overexpressing wild type GCase to an individual having a neurodegenerative disorder. The neurodegenerative disease may include lipid storage diseases, for example Gaucher disease, Parkinson's disease (PD), Dementia with Lewy bodies.

The disclosure relates to compositions and methods for altering, e.g., enhancing, the expression of GCase proteins, whether in vitro and/or in vivo. Such compositions include delivery of an adeno-associated viral (AAV) particle. The compositions and methods of the present disclosure are useful in the treatment of subjects diagnosed with, or suspected of having Parkinson Disease or related condition resulting from a deficiency in the quantity and/or function of GBA gene product or associated with decreased expression or protein levels of GCase protein.

The present invention relates to methods and compositions for treating a subject with a condition selected from: i) an on-going cytokine storm, ii) acute respiratory distress syndrome (ARDS), and/or iii) acute lung injury (ALI), using a composition comprising β-glucocerebrosidase, or a vector encoding β-glucocerebrosidase. In certain embodiments, the condition is caused by COVID-19 virus infection or other viral infection.

The present disclosure is directed to methods of treating a steatosis-associated disorder by administering a therapeutic agent selected from a lysosomal enzyme, an autophagy-inducing agent, or a combination thereof. Steatosis-associated disorders discussed herein include GSD Ia, GSD Ib, GSD Ic, NAFLD, and NASH. Other embodiments are directed to methods of reversing steatosis, modulating autophagy, inducing autophagy, and reversing glycogen storage.

A conjugate of a physiologically active polypeptide and immunoglobulin Fc with attenuated immune response is disclosed. Also disclosed are a method for preparing the conjugate, a composition for reducing an immune response including the conjugate, and a method for reducing the immune response of the physiologically active polypeptide. A method for maintaining the reduction in the intrinsic binding affinity of the conjugate for an Fc gamma receptor and/or a complement, and a composition including the conjugate are also disclosed.

Methods and compositions for treating Gaucher disease are described.

The present disclosure provides transposon-based methods of genetic editing in pluripotent stem cells, and methods of lineage specific differentiation of such edited pluripotent stem cells into floor plate midbrain progenitor cells, determined dopamine (DA) neuron progenitor cells, and/or DA neurons, or into glial cells, such as microglial cells, astrocytes, oligodendrocytes, or ependymocytes. Also provided are compositions and uses thereof, such as for treating neurodegenerative diseases and conditions, including Parkinson's disease.

The present invention provides compositions comprising one or more active pharmaceutical ingredients, wherein the compositions are in the form of high solids concentration pastes capable of being injected in relatively low volumes into an animal using standard commercially available syringes. The invention also provides methods of making such compositions, particularly those compositions comprising high molecular weight active ingredients (e.g., antibodies, enzymes and other proteins and peptides) at relatively high therapeutic concentrations in the high solids concentration pastes. The invention further provides methods of using such formulations in treating, preventing and/or ameliorating certain diseases and physical disorders in animals, including humans, in need thereof. The invention also provides kits comprising the formulations of the invention and a suitable syringe, which in some aspects may be pre-loaded or pre-filled with a composition of the invention.

The present invention is related to a dual promoter lentiviral vector and methods of use for the treatment of diseases and disorders, specifically lysosomal storage disorders.