The story was one of the biggest medical scandals of the second half of the 20th century.
Twenty years ago, neurologists first reported that 80 of an estimated 1,848 children treated with human growth hormone injections between 1959 and 1985 to prevent short stature subsequently developed a rare but devastating form of dementia called Creutzfeldt disease. Jacob (CJD). later in life. CJD is caused by abnormally shaped proteins called prions that infect the brain before spreading rapidly, causing other healthy proteins to change their shape and form toxic clumps, a process that results in progressive brain cell death.
Now neurologists from the UCL Institute of Prion Diseases have published a new study in NaturopathyThis suggests that another five children treated with growth hormone injections later developed Alzheimer’s disease between the ages of 38 and 55.
Peter Garrard, an honorary consultant neurologist at St George’s University Hospitals NHS Foundation Trust, said The Telegraph that he treated one of these five patients.
“He developed memory problems, and from a clinical perspective I had no hesitation in diagnosing him with Alzheimer’s disease,” says Garrard. “During the three years since I first saw him, he has made relentless and unfortunate progress so that his cognitive deficits are no longer limited to memory. He requires assistance with significant amounts of daily living.”
So how did this scandal happen?
A procedure that has now been banned
It sounds archaic by modern standards, but for much of the 20th century the only way to produce growth hormone was to remove the pituitary gland from the brains of deceased individuals who had donated their bodies to medicine.
These hormone-producing glands are located at the base of the brain, and doctors often had to collect glands from many different brain samples to collect enough growth hormone to perform a procedure. This was then injected into children in the hope that it would stimulate their growth, until the use of human-derived growth hormone was finally banned in 1985 after the health risks began to become apparent.
Growth hormone injections are still used in some rare cases of children with severely restricted growth, but this is now done entirely using synthetic forms of the hormone.
“Now all growth hormones are made in the laboratory, so it is completely safe,” says Prof. Jonathan Schott of the UCL Institute of Neurology. “It is important to point out that this was an outdated procedure at one point in time.”
What are prions?
In the 80 cases of children who developed CJD, the growth hormone they were given contained prions, which then entered their brains, with slow but fatal consequences. At the time, doctors did not understand the full implications of prion contamination and its connection to CJD.
Since the 1980s, we have learned that eating prion-contaminated meat can lead to a form of CJD known as mad cow disease. Research has also shown that cases of prion-induced diseases may result from human cannibalism. Papua New Guinea was hit by an epidemic neurodegenerative disease called kuru, which was spread via prions ingested by consuming human flesh.
“After someone died, as a sign of respect, there were feasts where the body and brains were eaten,” says Schott. “That has now stopped, but that was a way in which prions were passed on.”
What about these new five cases?
UCL neurologists are intrigued by the latest cases described in the Naturopathy study, as they may represent a novel mechanism by which Alzheimer’s disease can be transmitted.
The research team traced the original growth hormone samples injected into these five patients, which are still kept by the Ministry of Health. They found that they were not contaminated with prions, but contained some very small seeds of misfolded or abnormally shaped beta-amyloid proteins. .
Large toxic clumps of beta-amyloid have long been seen as one of the telltale signs of Alzheimer’s disease. Schott and others suggest that the misfolded beta-amyloid proteins may have behaved in a prion-like manner after being injected into patients, spreading throughout the brain and causing rapid damage.
“It was shown in the prion unit at UCL that if you took some of those beta-amyloid seeds and put them into mice, they could spread throughout the brain,” says Schott.
Do we have to worry?
Dementia researchers are keen to reassure the public that these new findings have no health implications from the procedures carried out today.
“We shouldn’t worry about the transmission of dementia between people, and we shouldn’t worry about surgical procedures,” said Prof Tara Spires-Jones, group leader at the UK Dementia Research Institute.
Schott points out that hospitals now have well-functioning safety procedures in place to prevent any chance of possible prion contamination. “It is not a contagious disease,” he says. “These were very, very tragic cases and this was a very unfortunate episode with some very special circumstances. There are a lot of measures now in terms of operations and so on to prevent the spread of prion diseases and other things.
Could this lead to new treatments for Alzheimer’s disease?
Instead, Schott believes the findings could help neurologists solve one of Alzheimer’s disease’s greatest enduring mysteries.
Although Alzheimer’s disease is linked to the presence of misfolded amyloid beta and tau proteins, we still don’t know how the disease then develops and spreads in the brain, something that is essential to understanding how we can treat it best to stop.
If misfolded beta-amyloid proteins can indeed behave like prions, moving from protein to protein and prompting them to change their shape in a destructive pattern, this could go some way to explaining how Alzheimer’s disease progresses.
“Prions form different shapes that then have the ability to self-replicate and spread,” says Schott. “One of the questions is whether beta-amyloid adopts similar characteristics and can thus grow and spread throughout the brain.”
However, not all dementia researchers are convinced. Spires-Jones accepts that the five patients who developed early Alzheimer’s disease were given seeds of beta-amyloid through a growth hormone injection and that these probably entered their brains.
However, she thinks it is too big a leap to suggest that these proteins behaved like prions purely on the basis of rodent studies. She points out that many healthy people have a significant presence of misfolded beta-amyloid in their brains in middle to late life and yet have no symptoms of Alzheimer’s disease.
“Most of us have a lot of misfolded amyloids in our brains, and we have no symptoms at all,” she says. “Your brain can handle that. To get Alzheimer’s disease you need a lot of amyloid and tau proteins, and then the loss of neurons, and we don’t know how the latter happens.”
However, Schott is hopeful that this will lead to more breakthroughs in understanding the progression of Alzheimer’s disease in the future.
“I think this is going to be a very fruitful area of research, and it could yield new ideas about how to stop the spread of Alzheimer’s disease as it becomes established,” he says.
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