Scientists have pinpointed the tiny, deadly flaw that triggers a ‘rusting’ of the brain in young children, causing devastating ‘baby Alzheimer’s.’
The discovery of this single genetic error not only explains a cruel childhood disease but could open the door to treatments for a host of neurodegenerative disorders like Alzheimer’s.
Researchers from Germany, Belgium, and the US traced the devastating conditions caused by a defect of the gene that provides the instructions for building the GPX4 enzyme in the brain, responsible for preventing a specific type of cell death caused by a rusting-type process called ferroptosis.
When defective, this gene causes neurons to ‘rust’ from the inside out and die, a process that may also be at play in common dementias such as Alzheimer’s, which affect roughly seven 7 million American seniors.
The researchers not only pinpointed the cause of childhood dementia but also, in early experiments, showed that they can slow this cellular rusting in the lab, offering the first concrete hope for a treatment.
Childhood dementia is a collection of more than 100 devastating disorders such as Sanfilippo syndrome, Batten disease, Alpers syndrome, and certain forms of mitochondrial diseases.
Individually, these conditions are rare; an estimated 12,000 children have dementia in the US, affecting about 1 in every 2,900 babies.
The average life expectancy of the conditions is 16, but some have lifespans as low as two.
Alivia (right), 12, was diagnosed with Sanfilippo syndrome, a rare genetic condition sometimes called childhood Alzheimer’s. She now functions at a toddler’s cognitive level and has lost the ability to walk, speak clearly or hold on to memories.
Professor Marcus Conrad, who led the research, likened GPX4 to a microscopic ‘surfboard.’
To work, it must stick a small, ‘fin-like’ loop into the inner wall of a neuron. As it ‘surfs’ along the membrane, it neutralizes toxic substances called lipid peroxides before they can cause damage.
In the case of a mutated gene, the enzyme does not do that.
The researchers studied three American children with a devastating early-onset dementia.
All shared the same tiny mutation in the gene for GPX4, which warps the crucial ‘fin.’
While ‘childhood dementia’ actually encompasses about 145 distinct brain disorders, the study did not explicitly state that the children had a specific named diagnosis, only that they fall under that broad umbrella.
Researchers took a skin cell sample from only one of the three kids and reprogrammed it into a stem cell. From that stem cell, they grew millions of human brain cells.
Next, they gave mice the same genetic mutation found in the children, allowing them to watch the disease progress in a living brain over time.
Brain scans reveal atrophy. MRI scans of three patients show progressive shrinkage of the cerebellum, the coordination center and, in two patients, shrinkage of the cerebral cortex, involved in memory and thinking. Ages at the time of each scan are shown
Alivia was diagnosed late after her early struggles were mistaken for ADHD and autism. Her aggressive form of the incurable disease causes rapid dementia and physical decline
Scientists discovered the same overactive cell-death pathway in both the diseased mice and human Alzheimer’s brains, revealing a shared target for treating a range of brain diseases.
Dr Svenja Lorenz, one of the first authors of the study, said: ‘Until now, dementia research has often focused on protein deposits in the brain, so-called amyloid beta plaques.
‘We are now putting more emphasis on the damage to cell membranes that sets this degeneration in motion in the first place.’
A Texas mother shared her daughter Alivia’s devastating diagnosis with Sanfilippo syndrome, one of the rare genetic disorders often referred to as childhood Alzheimer’s.
Now 12, Alivia functions at the cognitive level of a toddler and has lost the ability to walk, talk clearly, and retain memories.
She was diagnosed much later than most. Alivia’s early learning struggles were mistaken for ADHD and autism.
The terminal disease caused by a single gene mutation has no cure or treatment.
Children progressively lose their ability to walk, talk, and remember. This rare genetic disorder leads to severe cognitive and physical decline, with life expectancy rarely extending beyond the teenage years.
Meanwhile, in Ohio, a young couple’s two young children, Stella, 4, and Roman, 5, have been diagnosed with a rare genetic disorder known as ‘baby Alzheimer’s.’
Stella (center left) and Roman Arnold (center right) have a rare genetic condition that causes progressive neurological decline similar to Alzheimer’s disease in adults. They are pictured with their parents Donald (far left) and Jillian (far right)
Stella and Roman are defying the odds, having been given life expectancies of only three years. They have Acid Sphingomyelinase Deficiency (ASMD), a condition where a missing enzyme allows a fatty substance to accumulate and destroy cells in the brain, liver and spleen
Their children have the most severe form of Acid Sphingomyelinase Deficiency (ASMD), a condition where a missing enzyme allows a fatty substance to accumulate and destroy cells in the brain, liver and spleen.
The result is a rapid, irreversible neurological decline that mirrors Alzheimer’s disease in adults.
The typical life expectancy is just two to three years. The family’s only hope is a clinical trial that has extended the children’s survival.
Dr Adam Wahida, a first author of the study, said: ‘In the long term, we can imagine genetic or molecular strategies to stabilize this protective system. For now, however, our work clearly remains in the realm of basic research.’
Conrad added: ‘It has taken us almost 14 years to link a yet-unrecognized small structural element of a single enzyme to a severe human disease.
‘Projects like this vividly demonstrate why we need long-term funding for basic research and international multidisciplinary teams if we are to truly understand complex diseases such as dementia and other neurodegenerative disease conditions.’
Their study was published in the journal Cell.
[H/T Daily Mail]
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