PEGylated albumin for plasma expansion in ARDS caused by COVID-19

Description:

Project ID: D2001-06

Background
Capillary leakage of important ions and proteins, such as albumin from blood vessels can lead to a buildup of fluid in interstitial space (organ swelling) as well as hypoperfusion of organs. Capillary leak (CL) is a central component of multiorgan failure and a secondary component to severe sepsis caused by bacterial or viral infections, systemic inflammatory response syndrome (SIRS), and acute respiratory distress syndrome (ARDS). Systemic inflammation causes endothelial cell injury and cytokine release that exacerbates the CL. Current treatments utilize vasopressors and resuscitation with plasma volume expanders. However, there is still debate about their safety and side effects. For example, treating with additional albumin assumes the rate of extravasation will remain constant, but this is not true for some patients; the treatment can actually worsen CL by increasing albumin in the interstitium, further reducing oncotic pressure. Therefore, there is a need for a treatment option that will effectively prevent or treat hypovolemic conditions, such as ARDS.

Invention Disclosure
Researchers at the University of Toledo have developed a modified human albumin with a PEGylation product at multiple sites on the albumin protein. The PEGylated albumin (PEG-Alb) has a hydrodynamic radius that is sufficiently large enough to preclude its leaking through the capillaries while still retaining oncotic properties and its ability to bind ligands such as sodium ions, fatty acids, drugs, and bilirubin.  This was shown in an LPS model of shock and resulted in better blood pressure, hematocrit, and less lung injury compared to controls treated with unmodified albumin. Additionally, PEG-Alb was found to be more effective than albumin in maintaining blood pressure and hematocrit in the caecal ligation and puncture model of sepsis. In both models, labelled PEGylated albumin was found to be retained within the blood vessels. PEG-Alb increased the half-life of modified albumin, 5 times that of regular albumin.

Applications

  • Volume expansion in states of shock; i.e. ARDS, SIRS, sepsis, pancreatitis, burn and trauma
  • Hyperosmotic agent driving ultra-filtration in peritoneal dialysis, leukapheresis
  • Hyperviscosity states, nutritional albumin deficiency, hypoalbuminemic patients, nephrotic syndrome, anorexia
  • Patients with liver cirrhosis following parcenthesis or liver failure
  • Treatment of ARDS caused by COVID-19 and other viral infections, such as Dengue Fever and Ebola

Advantages

  • Decrease organ fluid extravasation
  • Longer half-life compared to albumin
  • Antioxidant effect, attenuates cytokines release due to CL
  • Decrease need for additional fluids during a state of hypotension

IP Status:             US 7,348,312, US 7,037,895, US 7,605,130, US 7,345,150, US 7,884,068

Publication:         Plasma expansion by polyethylene-glycol-modified albumin. Clinical Science (2004) 107, 263-272
                             Use of multiple fluorophores for evaluating microvascular permeability in control rats and rats with sepsis. Clinical Science (2008) 114, 123-130

Patent Information:
Category(s):
Inflammation
Immunity
For Information, Contact:
Stephen Snider
AVP Tech Transfer
The University of Toledo
419 530 6225
Stephen.Snider@utoledo.edu
Inventors:
Ragheb Assaly
J Dignam
Joseph Shapiro
Keywords:
Albumin
Capillary leakage
Plasma expanders