ProMetic Life Sciences Inc./vCJD Infection: A Continuing Threat To Public Health

Main Category: CJD / vCJD / Mad Cow Disease
Article Date: 04 Feb 2010 - 10:00 PDT


Variant Creutzfeldt-Jakob Disease ("vCJD") remains 'a very real and continuing threat to public health and recent developments strongly support predictions of second and third waves of long incubation vCJD' commented Dr Robert Rohwer, Director, Molecular Neurovirology Laboratory and Associate Professor of Neurology, University of Maryland, Baltimore, U.S., speaking at today's GovNet Communications' Patient Safety 2010 Conference held at the QEII Conference Centre in London, UK. Dr Rohwer went on to emphasize the urgency of implementing universal protective measures to arrest human to human transmission through blood transfusion and blood products.

Dr Rohwer highlighted recent research and developments showing how vCJD transmission risk remains 'very real'. He discussed the 'significant challenges' associated with detecting the prion in blood and urged implementation of proven infectivity removal technologies to protect blood. He referred to:

-- Research by Prof John Collinge of the National Prion Clinic, published in the Lancet, (December 2009) describing the first patient to succumb to vCJD from a previously unaffected genetic subgroup of the prion protein. Prior to this point, all 215 people who died of vCJD shared a certain version of the prion gene that is present in only one third of the population. This finding strengthens an earlier prediction by Prof Collinge of second and third waves of vCJD in people who were infected over the same period as people in the first wave, but whose genetics result in a longer incubation time. Two thirds of the population is in this group. Incubating cases in this longer incubation group may be spreading the infection through blood and tissue donations and other invasive medical procedures. These new routes of exposure are of special concern because person to person transmissions are expected to be much more efficient than cattle to person transmissions.

-- Research by the Scripps Research Institute, U.S. (January 2010) which revealed that prions evolve (change) to adapt to new environments. In these experiments prions mutated to more virulent strains and developed resistance to drugs used to suppress their propagation.

-- The exceptionally difficult challenge of detecting prions in blood or plasma. While the miniscule amounts of infectivity in blood is enough to cause infections, it has yet to be convincingly detected other than by infection. Normal forms of the prion protein exist in every person and in blood they are 100,000 to 1 million times more concentrated than the infectious forms. Other plasma proteins are a million times more concentrated than even the normal prion protein. In spite of an abundance of ingenuity and tremendous development effort there is still no blood based assay available for vCJD. Most recently (December 2009) one of the most advanced tests failed to detect prions in blood samples from clinical-stage patients who have died and been verified to have vCJD from animal studies. These patients are expected to have the highest concentrations of vCJD infectivity in their blood.

-- The estimation that the number of people incubating vCJD in the general population is anywhere between 1 in 4,000 and 1 in 20,000. These estimates presume a high level of efficiency in identifying incubating cases. In fact the efficiency is undetermined and at present undeterminable. The recent discovery of incubating infections of vCJD in persons who have died of other causes but have prion genotypes that have not previously resulted in clinically recognised cases suggests that the prevalence may be much greater than anticipated.

-- Universal leucodepletion (the removal of white blood cells from donated blood) was adopted by the UK in 1999, in part to diminish the risk from vCJD transmission by blood. Animal studies have since shown that leucodepletion removes only 40-70% of the infectivity in donated blood. The remaining infectivity is more than sufficient to transmit the infection.

Dr. Rohwer summarized: 'Currently, vCJD contaminated blood poses the greatest risk for human to human transmission of vCJD. Moreover, since the transmission is between humans rather than bovine to human and the exposure is by transfusion or injection rather than orally, it is expected to be at least 1,000 times more efficient than transmissions from BSE infected food. This is not a theoretical risk. To date there have been five recognized cases of transfusion transmission of vCJD and one highly probable transmission from a plasma product. The UK collects over 2.1 million blood donations annually (1.8 million in England alone). It is not known how many of these donors are incubating vCJD, but accumulating evidence of long incubation times in genotypes that make up approximately two thirds of the population intimates that it may be far greater than indicated by the cases detected to date.'

Dr Rohwer noted that the UK has been a leader in evaluating new approaches to reducing the risk from vCJD contamination of blood. These have included the P-Capt® prion reduction filter which removes prion infectivity with an efficiency of 99.9% or greater. The UK evaluation programme has led to a recommendation to the UK Department of Health by the Advisory Committee on the Safety of Blood, Tissues and Organs ("SaBTO") to deploy the P-Capt® filter for treatment of red blood cells destined for children born since 1 January 1996. On 27 October 2009 when it made this recommendation, SaBTO indicated that 'the requirement for prion filtration should be reviewed in the event that further data on vCJD prevalence or filter efficacy becomes available'. Dr Rohwer noted that all recent developments warn of a continuing risk from vCJD and that since the greatest risk of human to human transmission is from blood use, timely and universal adoption of the P-Capt® filter is urgently needed to arrest further spread of the disease.

Dr Rohwer welcomed the progress of the Contaminated Blood (Support for Infected and Bereaved Persons) Bill, a private member's bill that is due to receive its Second Reading in the House of Commons on 5 February. The Bill proposes using prion filtration to protect the haemophilia community from receiving blood which could be contaminated with infective prions that cause vCJD but cannot, as yet, be tested.

About variant Creutzfeldt-Jakob Disease

Variant Creutzfeldt-Jakob Disease ("vCJD") is characterized by the accumulation of large deposits of misfolded prion protein in the brain and the nervous system and the appearance of sponge-like holes in the brain causing a fatal degenerative CNS disorder. Such abnormal prion proteins may be sufficient to transmit the disease. Although some people's genetic make-up may protect them, at least 89% of the population may be susceptible to vCJD. vCJD was initially transmitted to humans from BSE infected cows presumably by the consumption of BSE contaminated meat, but a secondary route of transmission by the transfusion of blood units from asymptomatic vCJD individuals threatens to increase the prevalence of the fatal disease.

About P-Capt®

P-Capt® is a single-use sterile device which was awarded CE mark approval in September 2006. Red blood cells are passed through the filter under gravity and a highly specific affinity adsorbent material captures and removes any vCJD prion protein.

P-Capt® is the only approved product proven to be effective for the removal of prion infectivity from red blood cell concentrate prior to transfusion. It has been evaluated extensively by the UK Blood Services (including the National Blood Service, the Northern Irish Blood Transfusion Service, the Welsh Blood Service, and the Scottish National Blood Transfusion Service), the Irish National Blood Transfusion Service and the Health Protection Agency since production of the first batches in 2006 and to date has achieved all of the required performance and safety requirements and met all bench marks. The P-Capt® filter incorporates the prion-specific affinity resin developed by PRDT and supplied by ProMetic to MacoPharma and it is manufactured under licence and distributed by MacoPharma.

About Advisory Committee on the Safety of Blood, Tissues and Organs

Advisory Committee on the Safety of Blood, Tissues and Organs ("SaBTO") is a non-departmental public body with an independent Chair and members selected by the Appointments Commission for their specific areas of expertise. SaBTO's remit includes risk reduction measures to minimize the potential transmission of vCJD by transfusion and transplantation. In this context it has already recommended a ban on the transfusion of UK sourced plasma and that it be replaced with plasma sourced from other countries in order to avoid vCJD transmission. Five times more units of RBC are transfused compared with plasma and RBC must be sourced domestically.

About MacoPharma SA

MacoPharma SA ("MacoPharma") is an innovator in global healthcare with expertise in the fields of transfusion and infusion. It has become the largest supplier of in-line leucoreduction filtration sets in Europe and is expanding its efforts into the cellular therapy field by developing products for cell expansion, in addition to cell/organ processing and freezing. Headquartered in the Lille metropolitan area (France), MacoPharma has three manufacturing facilities in Europe and their products are sold into more than 55 countries worldwide.

Source
ProMetic Life Sciences Inc.

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