Human growth hormone, Creutzfeldt-Jakob disease...
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Sep 10, 2015  |  Vote 0    0

Human growth hormone, Creutzfeldt-Jakob disease and Alzheimer's linked

Patients injected with hormone who died of CJD had the same deposits in the brain that are associated with Alzheimer’s, British researchers find


Most people who die from the rare, fatal brain disorder known as Creutzfeldt-Jakob disease can blame either bad genes or bad luck. Of the roughly 50 cases reported in Canada every year, more than 95 per cent are hereditary or “sporadic” — random.

But in the 1970s, doctors realized to their horror that some patients injected with human growth hormone, which was then extracted from the pituitary glands of cadavers, had contracted this neurological disease. The procedure — used on 30,000 people worldwide, mostly children with stunted statures — transmitted misfolded proteins called prions, which incubated for decades before triggering death.

Now, British researchers writing in the journal Nature have reported that four middle-aged patients who received growth hormone injections 30 years ago and later died of Creutzfeldt-Jakob disease also had widespread amyloid-beta deposits in their brain, one of the pathological hallmarks of Alzheimer’s disease. The scientists believe the amyloid, another misfolded protein, was also transmitted in “seed” form via contaminated growth hormone.

Experts worldwide cautioned the report does not in any way suggest the public is at risk of being “infected” with Alzheimer’s. The use of cadaver-derived human growth hormone ceased in 1985, and there is no evidence that common medical procedures such as blood transfusions can transmit either Creutzfeldt-Jakob disease or Alzheimer’s.

John Collinge, the lead author of the Nature paper, wrote that “it is possible our findings might be relevant to some other medical or surgical procedures, but evaluating what risk, if any, there might be requires much further research.”

What the report does reveal is the first human evidence of a phenomenon that had already been noted in experiments on primates and mice. When laboratory animals are “seeded” with an extracted amyloid precursor protein, they later develop evidence of the pathology in their brains.

“It’s like one bad apple makes the whole barrel rotten, slowly,” said Sandra Black, a neurologist at the Sunnybrook Health Sciences Centre. Black, who was not involved in the study, called the finding “truly fascinating.”

“It’s illustrating that once you get these misfolded proteins happening and accumulating, they start to propagate each other — they start to make each other worse.”

Black, executive director of the Toronto Dementia Research Alliance, noted that the findings could provide a lift in the search for a dementia drug: It bolsters the theory that intervening early in the course of the disease may be key.

Collinge, director of the U.K.’s National Hospital for Neurology and Neurosurgery, is an expert on prion diseases, which are unusual because proteins, unlike bacteria or viruses, do not carry any genetic information.

In 1996 he showed that the same strain of prions that cause Bovine Spongiform Encephalopathy in cattle — mad cow disease — was also causing a new variant of Creutzfeldt-Jakob disease in humans, linking the latter to eating contaminated beef. His lab has been following a cohort of Britons with prion diseases of all kinds.

When eight patients who acquired the brain disorder from growth-hormone injections died, Collinge’s research team autopsied them. They found, “very much to our surprise,” that half had severe amyloid deposits in their brains, and another three had a lesser amount. Only one was amyloid-free — an especially striking result since the eight patients were between 36 and 51 when they died, far too young for the pathology to be common. None had genetic mutations leaving them at risk for early-onset Alzheimer’s.

Since autopsies of similarly aged prion-disease patients found no amyloid, the authors believe “seeds” of the amyloid proteins were also transferred via the growth hormone. But other researchers argued the amyloid buildup could have been caused by Creutzfeldt-Jakob disease itself, or some other mechanism.

Also interestingly, the patients’ brains did not show evidence of tau, the other hallmark of Alzheimer’s. Nor did they display clinical signs of dementia, such as memory loss: They did not have Alzheimer’s disease, only an unusual accumulation of a protein associated with it. Typical Alzheimer’s patients also do not show cognitive problems until the brain pathology is widespread, but Collinge’s team could not say whether the prion-disease patients might have developed full-blown Alzheimer’s had they lived longer.

Toronto Star

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