Safe and effective therapy discovered for patients with protein-losing enteropathy

Dec 07, 2007

Researchers at the Burnham Institute for Medical Research (Burnham Institute) have developed the first model to study intestinal protein leakage in mice, allowing the team to control and replicate both genetic deficiencies and environmental damages in an in vivo setting. Protein-losing enteropathy (PLE) encompasses conditions that involve the abnormal leakage of blood proteins into the digestive tract.

One type of PLE is observed in children who have undergone Fontan surgery, a procedure used to alleviate certain congenital heart defects. Half of post-Fontan patients who develop PLE die from this condition, due largely to therapeutic options that are inadequate and accompanied by serious side effects.

A study performed by the laboratory of Hudson Freeze, Ph.D., at the Burnham Institute has been published in the Journal of Clinical Investigation (JCI), describing both the science behind PLE and also a way to treat the disease that side steps some of the severe complications of current treatments.

Dr. Freeze’s group, led by Lars Bode, Ph.D., identified commonalities in clinical observations of PLE patients that recognized several key features of PLE pathogenesis; in particular, it is episodic and its onset is often associated with viral infection and a proinflammatory state. The most intriguing commonality that the group observed in PLE patients is the specific loss of heparan sulfate (HS) from intestinal epithelial cells during PLE episodes. Importantly, the study revealed that loss of HS is a key factor in promoting protein leakage and makes the intestine more susceptible to inflammation and increased hypertension. Co-author Simon Murch, M.D., University of Warwick, UK, first noticed the loss of intestinal cell HS in one of their previous collaborations.

“When heparan sulfate is missing, the inflammatory molecules pack a much greater punch and impact than when HS is there on the cell surface,” said Dr. Freeze, who is Professor and Co-Director of the Tumor Microenvironment Program at Burnham Institute.

The group had previously observed that soluble heparin compensates for loss of heparan sulfate and prevents protein leakage in vitro. However, long-term therapy with anticoagulant heparin has severe side effects, including bleeding, thrombocytopenia and osteoporosis. However, the study also revealed an alternative form of heparin as a potential therapy. By adapting well-established clinical assays to assess intestinal protein leakage in mice, Dr. Freeze’s team found that a heparin analog, 2,3-de-O-sulfated heparin, also prevented protein leakage both in vitro and in mice without causing bleeding. This compound exhibits greatly reduced anticoagulant activity, compared to unmodified heparin, which may mean that it can be used safely at much higher doses to treat PLE.

Source: Burnham Institute

Explore further: B and T cell-targeting drug ameliorates chronic graft-versus-host disease in mice

add to favorites email to friend print save as pdf

Related Stories

Unlocking the geoblock with VPNs

38 minutes ago

In recent months there have been many reports of Australians covertly signing up for the US streaming service Netflix, using fake postcodes and software workarounds to fool its geo-blocking system.

Measuring the height of the world's forests

48 minutes ago

If we know the height of the world's forests, then we can estimate how much carbon they store. That will improve our understanding of how forests interact with the atmosphere and their role in mitigating ...

New nanomaterial introduced into electrical machines

48 minutes ago

Lappeenranta University of Technology in Finland has constructed the world's first prototype electrical motor using carbon nanotube yarn in the motor windings. The new technology may significantly enhance the performance.

How the financial crisis boosted the best leaders

58 minutes ago

Six years on from the financial crisis and still many of us feel deeply unsure about institutions and individuals we had previously revered as beacons of reliability and certainty. The need to repair that ...

Recommended for you

Scientists aim to give botox a safer facelift

19 hours ago

New insights into botulinum neurotoxins and their interactions with cells are moving scientists ever closer to safer forms of Botox and a better understanding of the dangerous disease known as botulism. By comparing all known ...

User comments : 0