The story was one of the biggest medical scandals of the second half of the 20th century.
Two decades ago, neurologists first reported that 80 of an estimated 1,848 children treated with human growth hormone injections to prevent short stature between 1959 and 1985 developed a rare but devastating form of dementia called Creutzfeldt-Jakob disease (CJD). in his later life. CJD is driven by abnormally shaped proteins called prions, which infect the brain before spreading rapidly, causing other healthy proteins to change their shape and form toxic clumps, resulting in progressive brain cell death.
Now, neurologists at the UCL Institute of Prion Diseases have published a new study. Nature MedicineThis suggests that a further five 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, said: Telegram He said he treated one in five patients.
“He presented with memory problems, and from a clinical standpoint, I had no hesitation in diagnosing him with Alzheimer’s disease,” Garrard says. “Over the three years since I first saw him, he has made inexorable and unfortunate progress, such that his cognitive deficits are no longer limited to memory. “He needs help with an important part of daily life.”
So how did this scandal happen?
Now a banned procedure
It sounds ancient by modern standards, but for most of the 20th century, the only way to produce growth hormone was to remove the pituitary glands from the brains of deceased people who donated their bodies to medicine.
These hormone-producing glands are located at the base of the brain, and doctors often need to collect glands from many different brain samples to harvest enough growth hormone to perform a procedure. This was then injected into children in the hope that it would increase growth rates until the use of human-derived growth hormone was banned in 1985 after health risks began to emerge.
Growth hormone injections are still used in some rare cases of severely growth-restricted children, but this is now done entirely using synthetic forms of the hormone.
“All growth hormones are now completely safe because they are produced in the laboratory,” says Prof Jonathan Schott from the UCL Institute of Neurology. “It is important to note that this is an old procedure that has been outdated for some time.”
What are prions?
In the 80 cases of children who developed CJD, the growth hormone they received contained prions, which then slowly made their way into their brains with fatal results. At the time, doctors did not fully understand the effects 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-borne diseases may result from human cannibalism. Papua New Guinea was affected by an epidemic neurodegenerative disease called kuru, spread through prions ingested by consuming human flesh.
“After someone died, feasts were held where the body and brain were eaten as a sign of respect,” says Schott. “That too has now been stopped, but it was a way for prions to get through.”
What about these five new cases?
UCL neurologists intrigued by latest cases revealed in report Nature Medicine Because these may represent a new mechanism by which Alzheimer’s disease can be transmitted.
The research team tracked down the original growth hormone samples injected into these five patients, still stored by the Ministry of Health, and found that rather than being contaminated with prions, they contained tiny seeds of misfolded or abnormally shaped beta amyloid proteins. .
It has long been established that large clumps of toxic beta amyloid are one of the hallmarks of Alzheimer’s disease. Schott and others suggest that once misfolded beta amyloid proteins are injected into patients, they exhibit prion-like behavior, spreading throughout the brain and causing rapid damage.
“It has been shown in the prion unit at UCL that if you take some of these beta amyloid seeds and put them in mice, they can spread into the brain,” says Schott.
Should we be worried?
Dementia researchers want to reassure the public that these new findings do not carry any health implications associated with the procedures performed today.
“We shouldn’t be worrying about the transmission of dementia between people, and we shouldn’t be worrying about surgical procedures either,” says Prof Tara Spires-Jones, a group leader at the UK Dementia Research Institute.
Schott points out that hospitals now have well-developed safety procedures to prevent possible prion contamination. “This is not a contagious disease,” he says. “These were very, very tragic cases and this was a very unfortunate event over time with some very strange circumstances. “There are a lot of precautions now in surgeries 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 neurologists unravel one of the greatest mysteries of Alzheimer’s disease.
Although Alzheimer’s is linked to the presence of misfolded beta amyloid and tau proteins, we still do not know how the disease develops and spreads in the brain; This is vital to understanding how best to stop it.
If misfolded beta-amyloid proteins can indeed act like prions, moving from protein to protein, prompting them to change shape in a destructive pattern, this could go one way to explaining how Alzheimer’s progresses.
“Prions form a variety of shapes that then have the capacity to replicate and spread,” says Schott. “One question is whether beta amyloid takes on similar properties and can grow and spread in the brain in this way.”
But not all dementia researchers are convinced. Spires-Jones acknowledges that five patients who developed early-onset Alzheimer’s received beta-amyloid seeds through growth hormone injections, which likely progressed to their brains.
However, he thinks it would be a leap too far to suggest that these proteins must have behaved like prions based on rodent studies alone. He notes that many healthy people in middle and later years of life have been found to have significant amounts of misfolded beta amyloid in their brains, but without any symptoms of Alzheimer’s.
“Most of us have a bunch of misfolded amyloid in our brains and have no symptoms,” he says. “Your brain can handle it. “To get Alzheimer’s you have to have a lot of amyloid and tau protein, followed by neuron loss, and we don’t know how the latter happens.”
Schott is hopeful this will lead to further breakthroughs in understanding the progression of Alzheimer’s disease in the future.
“I think this will be a very productive area of research going forward, and it could lead to new ideas about how we can stop the spread of Alzheimer’s should it occur,” he says.
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