The present invention relates to methods for administering autologous and/or allogeneic B cells genetically modified to produce a therapeutic agent, such as a therapeutic protein. Specifically disclosed are methods for administering a single, maximally effective dose of genetically modified B cells and for administering multiple doses of genetically modified B cells. The compositions and methods disclosed herein are useful for the long-term, in vivo delivery of a therapeutic agent.

Provided are methods of treating subjects having, or at risk of having, heart disease, cardiovascular disease, coronary artery disease, cerebrovascular disease, acute or chronic renal disease, and/or symptoms thereof with certain therapeutically effective doses and dosing regimens comprising an isolated and purified lecithin-cholesterol acyltransferase (LCAT) enzyme, in particular, a recombinant human LCAT (rhLCAT) enzyme, e.g., MEDI6012. The methods involving administration of the described doses of rhLCAT increase serum levels of high density lipoprotein (HDL) and apolipoprotein A1 (apoA1) and decrease, or do not appreciably increase, serum levels of apolipoprotein B in the treated subjects, thus affording treatment of heart disease, heart-related diseases and coronary artery disease. The methods involving the described dosing regimens and doses of rhLCAT or MEDI6012 administered to a subject further provide cardio-, myocardio- and cardiovascular protection for the subject, including protection against ischemic stroke, myocardiocyte apoptosis, atherosclerosis progression and the like.

A synthetic or recombinant human lecithin cholesterol acyltransferase (LCAT) variant is provided which comprises an LCAT enzyme having a substitution at position 114 based on the residue numbering of wild-type (WT) human LCAT [SEQ ID NO:1], wherein said variant is characterized by one or more of: (i) an esterification rate higher than the esterification rate of WT human LCAT; and/or (ii) an association with higher density lipoprotein levels as compared to subjects having WT LCAT. Also provided are vectors encoding the variant, compositions containing same, and methods of using the variant proteins and vectors for treatment of a variety of disorders associated with defective wt LCAT.

A synthetic or recombinant human lecithin cholesterol acyltransferase (LCAT) variant is provided which comprises an LCAT enzyme having a substitution at position 114 based on the residue numbering of wild-type (WT) human LCAT [SEQ ID NO:1], wherein said variant is characterized by one or more of: (i) an esterification rate higher than the esterification rate of WT human LCAT; and/or (ii) an association with higher density lipoprotein levels as compared to subjects having WT LCAT. Also provided are vectors encoding the variant, compositions containing same, and methods of using the variant proteins and vectors for treatment of a variety of disorders associated with defective wt LCAT.

The present invention is related to a combination useful in the prevention and/or treatment of red blood cell disorders, in particular, acute and chronic complications associated with red blood cell dysfunction, increased red blood cell cholesterol and decreased plasma levels of lipophilic antioxidant (sickle cell disease, thalassemia, diabetes). The invention in particular relates to pharmaceutical formulations, regimens, methods of treatment and uses thereof.

The present invention is directed towards methods for treating non-alcoholic fatty liver disease (NAFLD) in a patient and determining prognosis of NAFLD in a patient.

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of a Lipid transport and metabolism gene, in particular, by targeting natural antisense polynucleotides of a Lipid transport and metabolism gene. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of a Lipid transport and metabolism genes.

A synthetic or recombinant human lecithin cholesterol acyltransferase (LCAT) variant is provided which comprises an LCAT enzyme having a substitution at position 114 based on the residue numbering of wild-type (WT) human LCAT [SEQ ID NO:1], wherein said variant is characterized by one or more of: (i) an esterification rate higher than the esterification rate of WT human LCAT; and/or (ii) an association with higher density lipoprotein levels as compared to subjects having WT LCAT. Also provided are vectors encoding the variant, compositions containing same, and methods of using the variant proteins and vectors for treatment of a variety of disorders associated with defective wt LCAT.

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of a Lipid transport and metabolism gene, in particular, by targeting natural antisense polynucleotide of a Lipid transport and metabolism gene. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of a Lipid transport and metabolism genes.

The present invention is related to a combination useful in the prevention and/or treatment of red blood cell disorders, in particular, acute and chronic complications associated with red blood cell dysfunction, increased red blood cell cholesterol and decreased plasma levels of lipophilic antioxidant (sickle cell disease, thalassemia, diabetes). The invention in particular relates to pharmaceutical formulations, regimens, methods of treatment and uses thereof.