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Study of UK patients with growth hormone-associated CJD points to a single prion strain

Nov 2016: Researchers from the National CJD Research & Surveillance Unit have studied the brains of people who developed CJD after receiving injections of human growth hormone.

When people in the UK hear of CJD they most often think of variant CJD, the form associated with the epidemic of BSE (“mad cow disease”). But prior to those events, UK patients who had been treated with injections of growth hormone purified from human pituitary glands unexpectedly developed CJD. This form of the disease is called human growth hormone associated iatrogenic CJD, or hGH-iCJD for short. It occurred as a result of contamination of the growth hormone preparations by prions, the transmissible agents causing CJD. The use of human growth hormone was abandoned in 1985 after the link to CJD was recognised, but cases of hGH-iCJD have continued to occur over the past thirty years.

National CJD Research & Surveillance Unit study

A Department of Health-funded team at the National CJD Research & Surveillance Unit and UCL led by James Ironside and Mark Head have performed a detailed study of the brains of growth hormone patients who developed hGH-iCJD from 1991 to the present day. They looked at the type of prion causing the disease, the genetics of the patients and the pattern of pathology found in the patients’ brains. They also modelled the replication of these prions in test tube molecular conversion assays. The resulting paper by Diane Ritchie, Marcelo Barria et al, is published in Acta Neuropathologica this month.

Molecular trace-back to single prion strain

The study found that the patterns of disease in the brain differed among people of different genotypes. In spite of this, the results show that hGH-iCJD could be explained by a single strain of prion, the V2 strain, which occurs in some cases of sporadic CJD. Moreover, the molecular conversion assays showed that this “protein-only pathogen” appears to “remember” its origin allowing a molecular trace-back to the likely source: a concept previously proposed by a Japanese team.

Implications for CJD surveillance

Although human growth hormone therapy was abandoned over thirty years ago, cases of hGH-iCJD still occur- the most recent patient died earlier this year.  These findings indicate that unrecognised or poorly assessed risks associated with medical interventions can have very long-term ramifications when it comes to prion safety. The study also underscores the importance of continued surveillance and deep phenotyping of cases of this rare but fatal and transmissible condition in order to determine the precise cause and to help protect public health.

Related links

Read the article in Acta Neuropathologica: doi:10.1007/s00401-016-1638-x

Prion disease research at the Centre for Clinical Brain Sciences

National CJD Research and Surveillance Unit

Prof James Ironside Principal Investigator profile

Dr Mark Head Principal Investigator profile