Provided herein are improved compositions and methods for enzyme replacement therapy using modified human cystathionine beta synthase (CBS) in the treatment of homocystinuria and related diseases and disorders.

The present invention provides a method of PEGylating a human truncated cystathionine β-synthase protein containing a mutation of a cysteine to a serine at amino acid position 15 (htCBS C15S). The htCBS C15S was PEGylated with one of 5 kDa, 10 kDa, or 20 kDa NHS ester PEG molecules. In-process monitoring of the PEGylation process was used in the method to reduce levels of unPEGylated htCBS C15S and htCBS C15S with insufficient PEGylation. Administration of the PEGylated htCBS C15S had efficacy throughout the course of treatment for homocystinuria.

The present disclosure describes the engineering of microbial cells for fermentative production of cystathionine and provides novel engineered microbial cells and cultures, as well as related cystathionine production methods. An engineered microbial cell that expresses a heterologous cystathionine beta-synthase or a heterologous cystathionine gamma-synthase, wherein the engineered microbial cell produces cystathionine.

The present disclosure provides formulations for a drug product comprising a PEGylated CBS protein having the amino acid sequence of SEQ ID NO: 1. Dosages and dosing regimens are provided for treatment of homocystinuria in a subject in need thereof. Additionally, the dosages and dosing regimens are also provided to reduce the level of homocysteine (Hcy) or increase the levels of cysteine (Cys) and/or cystathionine (Cth) in a subject in need thereof.

The present disclosure provides enzyme replacement therapy using gene therapy vectors, such as adeno-associated virus (AAV) vectors expressing human Cystathionine Beta-Synthase (CBS) to reduce the amount of serum homocysteine (Hcy) and increase the amount of downstream metabolites, such as cystathionine and cysteine (Cys), which can be used for treatment of diseases, such as homocystinuria and homocysteine remethylation disorders.

The present invention provides a method of PEGylating a human truncated cystathionine β-synthase protein containing a mutation of a cysteine to a serine at amino acid position 15 (htCBS C15S). The htCBS C15S was PEGylated with one of 5 kDa, 10 kDa, or 20 kDa NHS ester PEG molecules. In-process monitoring of the PEGylation process was used in the method to reduce levels of unPEGylated htCBS C15S and htCBS C15S with insufficient PEGylation. Administration of the PEGylated htCBS C15S had efficacy throughout the course of treatment for homocystinuria.

Provided are compositions and methods for enzyme replacement therapy using modified human cystathionine beta synthase (CBS) in the treatment of homocystinuria and related diseases and disorders.

Provided are compositions and methods for enzyme replacement therapy using modified human cystathionine beta synthase (CBS) in the treatment of homocystinuria and related diseases and disorders.

The present invention describes methods to produce a synthetic or semi-synthetic cysteine synthase/PLP-dependent decarboxylase (sCs/PLP-DC). More particularly, the invention relates to genetic modification of organisms including eukaryotes and prokaryotes to express a functional sCs/PLP-DC. The invention includes methods to produce taurine in organisms that contain native or heterologous (transgenic) taurine biosynthetic pathways or cells that have taurine by enrichment. The invention also relates to methods to increase taurine levels in the cells and to use the said cells or extracts or purifications from the cells that contain the invention to produce plant growth enhancers, food, animal feed, aquafeed, food or drink supplements, animal-feed supplements, dietary supplements, health supplements or taurine.

The present disclosure provides methods for treating homocystinuria or elevated homocysteine levels in subjects, including methods of improving cognitive function and ameliorating skeletal fragility, and methods of stratifying patient populations to determine disease progression or severity and/or to determine treatment regimens. In some embodiments, the methods of improving cognitive function in a subject having elevated total plasma homocysteine (tHcy) levels further comprise providing a cognitive or behavioral intervention.