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Transmission of amyloid-? protein pathology from cadaveric pituitary growth hormone.

ABSTRACT: We previously reported1 the presence of amyloid-? protein (A?) deposits in individuals with Creutzfeldt-Jakob disease (CJD) who had been treated during childhood with human cadaveric pituitary-derived growth hormone (c-hGH) contaminated with prions. The marked deposition of parenchymal and vascular A? in these relatively young individuals with treatment-induced (iatrogenic) CJD (iCJD), in contrast to other prion-disease patients and population controls, allied with the ability of Alzheimer's disease brain homogenates to seed A? deposition in laboratory animals, led us to argue that the implicated c-hGH batches might have been contaminated with A? seeds as well as with prions. However, this was necessarily an association, and not an experimental, study in humans and causality could not be concluded. Given the public health importance of our hypothesis, we proceeded to identify and biochemically analyse archived vials of c-hGH. Here we show that certain c-hGH batches to which patients with iCJD and A? pathology were exposed have substantial levels of A?40, A?42 and tau proteins, and that this material can seed the formation of A? plaques and cerebral A?-amyloid angiopathy in intracerebrally inoculated mice expressing a mutant, humanized amyloid precursor protein. These results confirm the presence of A? seeds in archived c-hGH vials and are consistent with the hypothesized iatrogenic human transmission of A? pathology. This experimental confirmation has implications for both the prevention and the treatment of Alzheimer's disease, and should prompt a review of the risk of iatrogenic transmission of A? seeds by medical and surgical procedures long recognized to pose a risk of accidental prion transmission2,3.

SUBMITTER: Purro SA

PROVIDER: S-EPMC6708408 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone.

Purro Silvia A SA Farrow Mark A MA Linehan Jacqueline J Nazari Tamsin T Thomas David X DX Chen Zhicheng Z Mengel David D Saito Takashi T Saido Takaomi T Rudge Peter P Brandner Sebastian S Walsh Dominic M DM Collinge John J

Nature 20181213 7736

We previously reported<sup>1</sup> the presence of amyloid-β protein (Aβ) deposits in individuals with Creutzfeldt-Jakob disease (CJD) who had been treated during childhood with human cadaveric pituitary-derived growth hormone (c-hGH) contaminated with prions. The marked deposition of parenchymal and vascular Aβ in these relatively young individuals with treatment-induced (iatrogenic) CJD (iCJD), in contrast to other prion-disease patients and population controls, allied with the ability of Alzh ...[more]

PMID: 30546139

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Project description:BackgroundThe study aimed to compare the growth responses to 3 years of growth hormone (GH) treatment in children and adolescents with GH deficiency (GHD) according to idiopathic, organic, isolated (IGHD), and multiple pituitary hormone deficiency (MPHD).MethodsTotal 163 patients aged 2-18 years (100 males and 63 females; 131 idiopathic and 32 organic GHD; 129 IGHD and 34 MPHD) were included from data obtained from the LG Growth Study. Parameters of growth responses and biochemical results were compared during the 3-year GH treatment.ResultsThe baseline age, bone age (BA), height (Ht) standard deviation score (SDS), weight SDS, mid-parental Ht SDS, predicted adult Ht (PAH) SDS, and insulin like growth factor-1 (IGF-1) SDS were significantly higher in the organic GHD patients than in the idiopathic GHD patients, but peak GH on the GH-stimulation test, baseline GH dose, and mean 3-year-GH dosage were higher in the idiopathic GHD patients than in the organic GHD patients. The prevalence of MPHD was higher in the organic GHD patients than in the idiopathic GHD patients. Idiopathic MPHD subgroup showed the largest increase for the ΔHt SDS and ΔPAH SDS during GH treatment, and organic MPHD subgroup had the smallest mean increase after GH treatment, depending on ΔIGF-1 SDS and ΔIGF binding protein-3 (IGFBP-3) SDS. The growth velocity and the parental-adjusted Ht gain were greater in the idiopathic GHD patients than the organic GHD patients during the 3-year GH treatment, which may have been related to the different GH dose, ΔIGF-1 SDS, and ΔIGFBP-3 SDS between two groups. Multiple linear regression analysis revealed that baseline IGF-1 SDS, BA, and MPH SDS in idiopathic group and baseline HT SDS in organic group are the most predictable parameters for favorable 3-year-GH treatment.ConclusionThe 3-year-GH treatment was effective in both idiopathic and organic GHD patients regardless of the presence of MPHD or underlying causes, but their growth outcomes were not constant with each other. Close monitoring along with appropriate dosage of GH and annual growth responses, not specific at baseline, are more important in children and adolescents with GHD for long-term treatment.Trial registrationClinicalTrials.gov Identifier: NCT01604395.

Dataset Information

Transmission of amyloid-? protein pathology from cadaveric pituitary growth hormone.

Publications

Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone.

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