The Unfolding Story of Protein Misfolding Causing Alzheimer Disease in Recipients of Human Pituitary Growth Hormone

Human growth hormone (hGH) has been in clinical use for children with GH deficiency (GHD) since the late 1950s. The original formulations were considered very safe with few adverse events reported. That changed remarkably in 1985 when the first patients with GHD, who had been treated with cadaveric hGH, were diagnosed with Creutzfeldt-Jakob disease (CJD). Fortunately, that same year a robust supply of recombinant hGH was released to the market whose adverse event profile did not include CJD. Patients who had received National Hormone and Pituitary Program hGH have been continuously followed since 1985. It is clear that prions are causative for CJD. Within the last 10 years there have been reports that similar preparations of cadaveric hGH may have been contaminated with amyloid β (Aβ) protein, a material that is related to Alzheimer disease. Eight patients in the United Kingdom, who had received cadaveric hGH extracted in an analogous manner to that in the United States, had conditions compatible with Alzheimer disease, although they did not fulfill all of the requirements for that diagnosis. In this report we discuss the findings of both CJD and Alzheimer disease, especially as they relate to a possible transmission of the diseases by prions and Aβ protein.