To make Hemopure 'we take bovine blood and, using filtration and chromatography, purify the haemoglobin so it is 99.9 per cent pure protein,' explains Light. But sadly it isn't as simple as just dissolving the haemoglobin in a fluid and transfusing it into the patient. Native haemoglobin is tetrameric and dissociates into dimers in the body that are excreted through the kidneys with a half life of about 30 minutes. 'Which is not a very effective therapy,' Light points out. 'You have to modify the haemoglobin so it doesn't dissociate.'
A number of different approaches have been taken to stop this dissociation. 'What we do is polymerise with glutaraldehyde [pentane-1,5-dial] to make large polymers of haemoglobin that have a half life of between 18 and 24 hours in the body,' Light says.
The polymerised haemoglobin is then put into a physiological buffer, which contains salts and lactates to maintain heart function. At this stage the product still contains about 30 per cent stabilised haemoglobin tetramers - and while they may not dissociate in this form, they are still problematic because they can enter blood vessel walls and scavenge nitric oxide. NO naturally causes the walls of blood vessels to relax, so if too much NO is scavenged, relaxation is prevented, making it more difficult for blood to flow, resulting in an increase in blood pressure. A final clean up stage removes most of the tetramer haemoglobin, significantly reducing the blood pressure effect, explains Light.
Once transfused into the body, polymerised haemoglobin works in the same way as a red blood cell: it binds to oxygen in the lungs, carries it to the appropriate site in the body and then releases it. What makes it different to red blood cells is that the haemoglobin is free in the plasma - rather than bound within the cell.
The advantage of the haemoglobin being in the plasma is that the oxygen it carries is closer to the sides of blood vessels. Oxygen binding and release in the plasma is more efficient than in the red cell, says Light, so Hemopure releases oxygen more quickly than donor blood once it gets to the target tissue. At end of its life, Hemopure is broken down by the normal biological pathway for haemoglobin.
Hemopure is currently approved for use in South Africa, and has undergone some early clinical trials in the US. Production stopped, however, when Biopure went bankrupt - and OPK Biotech is currently focusing on getting production back online. Referring to the FDA's concerns over these products, Light predicts that they will be approved overseas before approval in the US. The firm's parent company, OPK, is Russian and, according to Light, 'OPK have a great interest in bringing this product to Russia.'
