Feb 8, 2010 - Study at the Karolinska Institute suggests potential for reducing the high death rate from sepsis, one of the top-10 causes of death in the U.S.

Study at the Karolinska Institute suggests potential
for reducing the high death rate from sepsis,
one of the top-10 causes of death in the U.S.
Study results published in current issue of ASAIO Journal

BERKELEY, Calif., Feb. 8, 2010—ExThera Medical announced today that the results of a preliminary study (“Cytokines in blood from septic patients interact with surface immobilized heparin”) of its proprietary medical device, Seraph™ extracorporeal affinity therapy, have been published in the current issue of the Journal of the American Society for Artificial Organs (Jan.-Feb. 2010).

One very important clinical application of Seraph (Selective Removal by Apheresis) is expected to be the treatment of sepsis within intensive care units. Seraph consists of a specially designed cartridge packed with a novel bioactive polymer substrate that acts as a hemofilter. By incorporating immobilized heparin, the cartridge’s high-surface-area can safely and selectively reduce cytokine levels and remove certain pathogens from a patient’s blood before the blood is (re)infused.

In the study conducted at the Karolinska Institute in Stockholm, Sweden, when blood from septic patients was passed through a miniature version of the Seraph cartridge, concentrations of pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) were “significantly reduced from initially very high levels.” In the control group, passage of blood from septic patients over non-heparinized beads did not affect the TNF- α levels. “We conclude that surface heparinization may be a useful technique for selectively regulating the levels of heparin-binding cytokines from whole blood. This may have implications for the treatment of hyper-inflammatory conditions such as severe sepsis,” said principal investigator Jonas Axelsson, M.D., Ph.D., of Karolinska Institute’s Department of Renal Medicine.

“The removal of blood-borne pathogens by adsorption onto heparinized surfaces such as Seraph may become a viable method for treating sepsis patients at both the onset and advanced stage of the disease,” said George Pitarra, President and Managing Director of Emergence LLC. “Although a considerable amount of clinical work remains to be done, we are extremely encouraged by the results of the Karolinska study.”

“It is well-established that heparin can bind an enormous variety of peptides with high specificity at the appropriate binding sites,” added Olle Larm, Ph.D., CEO of ExThera AB. “In addition to the affinity of heparin for cytokines, heparin also is capable of binding the pathogens responsible for the onset of sepsis as previously demonstrated during our earlier in vitro experiments and now in this ex vivo study at the Karolinska Institute. Apheresis based on a bioactive heparinized polymer surface such as Seraph avoids the constraints of drugs, which typically target only one pathogen and do not affect the cytokine level. The combination of specific removal of cytokines and the removal of pathogens from the blood stream may give clinicians a new paradigm for treating septic patients.”

“The use of bioactive synthetic polymers to treat or even cure disease may open a whole new area of application for biomaterials—which have previously been used after the fact—to rebuild, replace or augment body parts already damaged by disease and trauma,” added Bob Ward, Chairman of Emergence LLC. “I am very happy to be working on this project with Professor Olle Larm and his team, as Dr. Larm pioneered the surface heparinization of biomaterials in blood contacting medical devices.”

About Seraph™
Selective Removal by Apheresis (Seraph™) is based on the unique binding capacity of the immobilized, naturally occurring heparin molecule. Disease-causing microorganisms use cell surface glycoconjugates such as heparin as receptor molecules for cell attachment, e.g., to facilitate their invasion and colonization of tissue. Similar receptors can be built into a polymer surface for selective removal of these microorganisms from blood. ExThera Medical is investigating the clinical impact of the ability of immobilized heparin to bind viruses, bacteria, parasites and excess cytokines in blood, while developing both therapeutic products to treat patients in the clinic, and devices that purify blood prophylactically before (re)perfusion. Both product types treat blood in a flow-through Heparin Affinity Apheresis™ column or cartridge, using heparin that has been chemically bonded to a novel polymer with precisely controlled surface chemistry and nano-structure. Smaller cartridge-type devices may also be effective in reducing iatrogenic disease associated with conventional extracorporeal blood-handling, including kidney dialysis, cardio-pulmonary bypass, and even blood-banking. In these circuits the inflammatory cascade is initiated when blood contacts a man-made surface, releasing proteins and cell aggregates into the circulating blood. This can lead to brain damage and other complications related to the activation of the inflammatory system. ExThera Medical’s Seraph.

About Sepsis
Sepsis is a condition that results from the immune system’s response to severe infection leading to cardiovascular collapse and multiple organ failure. It is one of the top-ten causes of death in the U.S., killing over 225,000 Americans each year, more than lung and breast cancer combined. Severe sepsis has reported mortality rates ranging from 30 to 60 percent, and an average cost of $22,100 per case. Over three quarters of a million new cases of sepsis are identified in the U.S. annually, with an equally large case population in Europe and Asia. The disease typically attacks the elderly and its incidence is expected to increase with the aging population, and as more pathogens develop resistance to antibiotics. A research study performed at Emory University and the Centers for Disease Control concluded that the incidence of sepsis increased an average of 8.7 percent a year over the past two decades. Patients with severe sepsis require intensive care and account for a large proportion of ICU resource allocation.

About ExThera Medical
Privately held ExThera Medical, based in Berkeley, Calif., is a joint venture company formed in 2007 by Emergence LLC, a life science incubator headquartered in Berkeley, Calif., and ExThera AB, a technology transfer partner of Karolinska Institute based in Stockholm, Sweden. ExThera Medical is targeting the clinical treatment of blood-borne diseases including sepsis and autoimmune disease, as well as the removal of harmful substances present in banked human blood and/or caused by contact with man-made materials during cardiopulmonary bypass, dialysis and other extracorporeal procedures.