Provided herein are thiosuccinyl-crosslinked hemoglobin analogs useful as blood replacement agents, pharmaceutical compositions comprising the same and the methods of use and preparation thereof.

A Direct Sodium Removal method, apparatus and solution for treating patients in heart failure, and having a glomerular filtration rate greater than 15 mL/min/1.73 m.sup.2, or residual kidney function corresponding to normal to CKD Stage 4, is provided in which a no or low sodium DSR infusate is administered to the peritoneal cavity for a predetermined dwell period and then removed, thereby removing sodium from the body. The resulting elimination of fluid from the patient by i) functioning of the kidneys through urination and ii) direct removal of osmotic ultrafiltrate from the peritoneal cavity, restores serum sodium concentrations to healthy levels and thereby reduces fluid overload in the patient.

A Direct Sodium Removal method, apparatus and solution for treating patients in heart failure, and having a glomerular filtration rate greater than 15 mL/min/1.73 m.sup.2, or residual kidney function corresponding to normal to CKD Stage 4, is provided in which a no or low sodium DSR infusate is administered to the peritoneal cavity for a predetermined dwell period and then removed, thereby removing sodium from the body. The resulting elimination of fluid from the patient by i) functioning of the kidneys through urination and ii) direct removal of osmotic ultrafiltrate from the peritoneal cavity, restores serum sodium concentrations to healthy levels and thereby reduces fluid overload in the patient.

A direct sodium removal (“DSR”) infusate regimen and methods of use are provided for removing sodium and reducing fluid overload in patients with severe renal dysfunction and/or heart failure, in which a patient has at least a first DSR session with a first DSR infusate having no or low sodium that is instilled into a patient's peritoneal cavity for a first dwell period to cause sodium and excess fluid to migrate to the patient's peritoneal cavity, and thereafter, the patient may undergo conventional dialysis to rebalance the patient's fluid and sodium levels.

A direct sodium removal (“DSR”) infusate regimen and methods of use are provided for removing sodium and reducing fluid overload in patients with severe renal dysfunction and/or heart failure, in which a patient has at least a first DSR session with a first DSR infusate having no or low sodium that is instilled into a patient's peritoneal cavity for a first dwell period to cause sodium and excess fluid to migrate to the patient's peritoneal cavity, and thereafter, the patient may undergo conventional dialysis to rebalance the patient's fluid and sodium levels.

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.

The invention relates to mRNA therapy for the treatment of Acute Intermittent Porphyria (AIP). mRNAs for use in the invention, when administered in vivo, encode human porphobilinogen deaminase (PBGD), isoforms thereof, functional fragments thereof, and fusion proteins comprising PBGD. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to affect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of PBGD expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient PBGD activity in subjects, namely porphobilinogen and aminolevulinate (PBG and ALA).

The invention relates to mRNA therapy for the treatment of Acute Intermittent Porphyria (AIP). mRNAs for use in the invention, when administered in vivo, encode human porphobilinogen deaminase (PBGD), isoforms thereof, functional fragments thereof, and fusion proteins comprising PBGD. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to affect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of PBGD expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient PBGD activity in subjects, namely porphobilinogen and aminolevulinate (PBG and ALA).

Provided herein are thiosuccinyl-crosslinked hemoglobin analogs useful as blood replacement agents, pharmaceutical compositions comprising the same and the methods of use and preparation thereof.

Provided herein are thiosuccinyl-crosslinked hemoglobin analogs useful as blood replacement agents, pharmaceutical compositions comprising the same and the methods of use and preparation thereof.