Jakob-Creutzfeld disease

This working party considers the aspects of the manufacture and control of biotechnological and biological medicinal products and is also involved in the provision of scientific advice. Workshops on the applieation of assays for markers of transmissible spongiform encephalopathies (TSE) and on the potential risk of transmitting new variant Creutzfeld-Jakob disease (nv-CJD) through plasma-derived medicinal products have recently been held. 

Infectious Dementias. One hundred years ago, the most common cause of dementia was an infection syphilis. Today, syphilis is well treated and seldom left to linger long enough to infect the brain and cause dementia, but a blood test for syphilis remains a routine part of the assessment for patients newly diagnosed with dementia. Today, the most common infectious cause of dementia is HIV/AIDS. Other, rare forms of infection-caused dementia include Creutzfeld-Jakob disease (spongiform encephalopathy) and subacute sclerosing panencephalitis (SSPE), the latter caused by the measles virus in unvaccinated children. 

The prion protein (PrP) is an infectious protein that converts noninfectious PrP into the infectious form, which precipitates. PrP is implicated as the causative agent of the transmis sible spongiform encephalopathies, including Creutzfeld-Jakob disease. 

The inescapable variability of the source material and potential threat to safety due to unrecognized infectious agents [transmission ofAIDS by blood products and the undefined potential for either human or bovine source materials to spread Creutzfeld-Jakob disease (CJD)/ transmissible or bovine spongiform encephalopathy (TSE, BSE)]... 

Human blood, given by blood donors, is a source not only of cellular material (red cells, white cells, platelets) but also of blood plasma, which is subjected to protein fractionation to give albumin, anti-hemophilia factors and immunoglobulins. The possibility of transmission of Creutzfeld-Jakob disease (CJD) - prions are not really understood - and acquired immune deficiency syndrome (AIDS), if sterilization procedures fail, combined with the feasibility of manufacturing proteins by recombinant DNA technology, mean that there is uncertainty about the long-term future of the blood products industry. Indeed, the problems with bovine spongiform encephalitis (BSE) and the related fatal human brain disorder, CJD, have led to unease about cattle-derived substances. 

A fresh boost was given to plant-based molecular farming in recent years, as the biopharmaceutical industry is trying to eliminate manufacturing processes that rely on production in animal cells due to the possible contamination of these products by human pathogens such as bovine spongiform encephalopathy (BSE) or Creutzfeld-Jakob disease (CJD, vCJD) (see-Part IV, Chapters 1, 2, 3, and 4). 

These transmissible diseases, with insoluble protein as the infectious agent, would seem to have originated as mutations, and within this context they became inherited prion diseases. Creutzfeld-Jakob disease, GSS, and FFI number among those now recognized as inherited prion diseases in humans. 

The epidemic of mad cow disease that resulted in the loss of upwards of 200,000 cattle apparently arose due to feeding cattle a meal that contained contaminated neural tissue. Animal feed containing nervous tissue is considered to be the source of prion diseases occurring in sheep and goats. There also appears to be cross-infectivity between species, as scores of humans have contracted a variant form of Creutzfeld-Jakob disease (vCJD) from eating contaminated beef " ... 

Of note, human-derived dural replacement products became popular in the 1960s, employing freeze-dried cadaveric dural grafts. However, these allogeneic grafts presented additional risks as serious infections were reported, including prion (eg, Creutzfeld-Jakob) disease and lentivirus transmission (Centers for Disease Control and Prevention, 2008 Walcott et al., 2014), and thus were discontinued from use. 

There are morphologial similarities between amyloid protein and infectious protein in scrapie and Creutzfeld-Jakob disease, and protein deposits in Alzheimer s disease, all of which are associated with progressive and irreversible degeneration of nervous function, leading to death. [P.A.Merz etal. Nature 306 (1983) 474- 76 H.Diringer etal. ibid. 476-478] In Alzheimer s disease there is invariably a progressive accumulation of filamentous aggregates of amy-... 

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