Ethics in prion disease

Abstract

This paper is intended to discuss some of the scientific and ethical issues that are created by increased research efforts towards earlier diagnosis, as well as to treatment of, human prion diseases (and related dementias), including the resulting consequences for individuals, their families, and society. Most patients with prion disease currently are diagnosed when they are about 2/3 of the way through their disease course (Geschwind, Kuo et al. 2010; Paterson, Torres-Chae et al. 2012), when the disease has progressed so far that even treatments that stop the disease process would probably have little benefit. Although there are currently no treatments available for prion diseases, we and others have realized that we must diagnose patients earlier and with greater accuracy so that future treatments have hope of success. As approximately 15% of prion diseases have a autosomal dominant genetic etiology, this further adds to the complexity of ethical issues, particularly regarding when to conduct genetic testing, release of genetic results, and when or if to implement experimental therapies. Human prion diseases are both infectious and transmissible; great care is required to balance the needs of the family and individual with both public health needs and strained hospital budgets. It is essential to proactively examine and address the ethical issues involved, as well as to define and in turn provide best standards of care.

Prion Diseases

“…Tikvah Alper, Ian Pattison, and others postulated that the “scrapie agent” did not contain nucleic acid and might be a protein. 5,6 Researchers later showed that transmission of the transmissible spongiform encephalopathy causative agent from animal to animal could be prevented by treating the tissue using methods that destroy and denature proteins. 5,6 Stanley Prusiner received the 1997 Nobel Prize in Physiology or Medicine in part for isolating the scrapie agent and confirming it was a misfolded protein, which he called a “proteinaceous infectious particle,” or prion.…”

“…5,6 Researchers later showed that transmission of the transmissible spongiform encephalopathy causative agent from animal to animal could be prevented by treating the tissue using methods that destroy and denature proteins. 5,6 Stanley Prusiner received the 1997 Nobel Prize in Physiology or Medicine in part for isolating the scrapie agent and confirming it was a misfolded protein, which he called a “proteinaceous infectious particle,” or prion. 5 Although Dr Prusiner’s “prion hypothesis” has been controversial for many years, accumulating evidence over the past several years has confirmed the prion hypothesis beyond any reasonable doubt.…”

Creutzfeldt-Jakob disease associated with a V203I homozygous mutation in the prion protein gene

“…Approximately 85-90 % of CJD cases are sporadic (sCJD) lacking any mutations in the prion protein gene (PRNP), while about 10-15% of the disorders are inherited. 1 Familial CJD (fCJD) is associated with at least 20 distinct genetic mutations that are all transmitted as autosomal dominant traits, including point, deletion and insertion mutations. 2 Most of the mutations that cause fCJD, are heterozygous.…”

Age of onset in genetic prion disease and the design of preventive clinical trials

“…To date, all completed clinical trials in prion disease have recruited only symptomatic patients, mostly with sporadic prion disease, and have used cognitive, functional, or survival endpoints [7][8][9][10][11][12][13][14] . By the time of diagnosis many prion disease patients are in a state of advanced dementia, and even a therapy that halted the disease process entirely at this stage might only preserve the patient in a state with little or no quality of life 15 . Moreover, preclinical proofs of concept argue that a preventive, rather than therapeutic, approach is more likely to be effective.…”