by 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 out of about 1,848 children treated with human growth hormone injections between 1959 and 1985 to prevent short stature went on to develop a rare but devastating form of dementia called Creutzfeldt-Jakob (CJD), later in life. CJD is driven by abnormal proteins called prions that infect the brain before spreading rapidly, prompting otherwise healthy proteins to change shape and form toxic clumps, a process that leads to progressive brain cell death.
Now, neuroscientists at the UCL Institute of Prion Diseases have published a new study in Nature Medicinesuggesting that five other children treated with growth hormone injections later developed early-onset Alzheimer’s between the ages of 38 and 55.
Peter Garrard, honorary consultant neurologist at St George’s University Hospitals NHS Foundation Trust told The Telegraph that he has treated one of these five patients.
“He presented with memory problems, and clinically I had no hesitation in diagnosing Alzheimer’s disease,” says Garrard. “Over the three years since I first saw him, he has progressed in a relentless and relentless way, 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 is now prohibited
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 glands from the brains of deceased people who had given their bodies to medicine.
These hormone-producing glands are located at the base of the brain and often doctors would have to collect glands from many different brain samples to gather enough growth hormone to perform a procedure. This was then injected into children in the hope that it would increase their growth rate, until the use of human-derived growth hormones was banned in 1985 when health risks became apparent.
Growth hormone injections are still used in some rare cases of children with severe growth restriction, but this is now done entirely using synthetic forms of the hormone.
“Now, all growth hormones are made in the laboratory so it’s completely safe,” says Professor Jonathan Schott from the UCL Institute of Neurology. “It’s important to point out that this was an outdated legacy procedure from time to time.”
What is a prince?
In the 80 cases of children who developed CJD, the growth hormone they received contained prions, which then progressed into their brains with slow but fatal consequences. At the time, doctors did not understand the full implications of prion contamination and the link 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 can result from human cannibalism. Papua New Guinea was hit by an epidemic neurodegenerative disease called kuru that was spread by ingesting princes by eating human flesh.
“After someone died, as a sign of respect there were feasts where the body and brain were eaten,” says Schott. “That’s stopped again now, but that’s the way prions were run.”
What about these five new cases?
UCL neuroscientists are excited by the latest cases reported in the Nature Medicine study, as they may reveal a new mechanism by which Alzheimer’s disease can be transmitted.
The research team traced the original growth hormone samples injected into those five patients, which are still stored by the Department of Health, and found that they contained some very small seeds of misfolded or abnormally shaped beta-amyloid proteins rather than be contaminated with prions. .
Large toxic clumps of beta-amyloid have long been cited as one of the telltale signs of Alzheimer’s disease. Schott and others suggest that the misfolded amyloid beta proteins may behave in a prion-like manner after being injected into patients, spreading through the brain, and causing rapid damage.
“The prion unit at UCL showed that if you took some of those amyloid beta seeds and put them into mice, they could spread through the brain,” says Schott.
Should we be worried?
Dementia researchers are trying to reassure the public that these new findings have no health implications for procedures performed today.
“We shouldn’t worry about dementia passing between people and we shouldn’t worry about surgical procedures,” says Professor Tara Spires-Jones, group leader at the UK’s Dementia Research Institute.
Schott points out that hospitals now have well-functioning safety procedures in place to prevent any chance of prion contamination. “It’s not an infectious disease,” he says. “These were extremely tragic cases and this was very unfortunate given the passage of time and very specific circumstances. There’s a lot going on now in surgery and so on to prevent the spread of prion disease and other things.”
Could it lead to new Alzheimer’s treatments?
Instead, Schott believes the findings could help neuroscientists solve one of the biggest mysteries of Alzheimer’s disease.
Although Alzheimer’s is associated with the presence of amyloid beta and tau proteins, we still do not know how the disease develops and spreads within the brain, which is crucial to understanding how best to stop it.
If amyloid beta proteins can indeed behave like prions, moving from protein to protein and being induced to change their shape in a destructive pattern, it would go some way to explaining the progress at Alzheimer’s.
“Principles create different shapes that have the ability to replicate themselves and spread,” says Schott. “One of the questions is whether beta-amyloid takes on similar characteristics and that’s how it’s able to grow and spread throughout the brain.”
Not all dementia researchers are convinced, however. Spiers-Jones assumes that the five patients who developed early-onset Alzheimer’s received beta-amyloid seeds by injection of growth hormone and that these probably spread to their brains.
However, she feels it is premature to suggest that these proteins must be behaving like princes, based on rodent studies alone. She points out that many healthy people in later life have been found to have a significant presence of amyloid beta in their brains, and still have no signs of Alzheimer’s.
“Most of us have a bunch of misfolded amyloid in our brain, and we don’t have any symptoms,” she says. “Your brain can cope with that. To have Alzheimer’s, you have to have a lot of amyloid and tau proteins, then loss of neurons, and we don’t know how that happens.”
Schott is optimistic, however, that this will lead to more breakthroughs in understanding the progression of Alzheimer’s in the future.
“I think this is going to be a very fruitful area of research going forward, and if it’s successful, it may open up new ideas about how we might stop Alzheimer’s from spreading,” he says.
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