Posted on 05/04/2022 9:58:11 AM PDT by Red Badger
Differences in Pitt-Hopkins Syndrome (right) and a control (left) organoid. (Papes et al., Nature Communications, 2022)
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Scientists have uncovered changes in neurological structure that could underlie the autism spectrum disorder known as Pitt Hopkins syndrome, thanks to the help of lab-grown brains developed from human cells.
Furthermore, the researchers were able to recover lost genetic functions through the use of two different gene therapy strategies – hinting at the possibility of treatments that could one day give those with the condition new options in improving their quality of life.
Pitt Hopkins syndrome is a neurodevelopmental condition stemming from a mutation in a DNA-management gene called transcription factor 4 (TCF4). Classed on the autism spectrum on account of its severe impact on motor skills and sensory integration, it's a complex condition that presents with a range of severities.
What's more, changes in the TCF4 gene are associated with other forms of autism and diverse neurodevelopmental conditions, including schizophrenia.
In spite of its clear significance in our brain's development, we know surprisingly little about the gene's mechanisms, neither in its typical or mutated forms.
Researchers from the University of Campinas in Spain and the University of California San Diego (UC San Diego) aimed to change this by studying the workings of the genes in an environment as close to a developing brain as they could ethically get.
Skin cells taken from volunteers with a diagnosis of Pitt Hopkins syndrome were reprogrammed into stem cells that formed the foundations of a brain-like mass, called a brain cortical organoid.
Organoids are simplified versions of a real brain, incapable of performing all of the functions expected of an actual organ. Yet they do help researchers study aspects of the brain, demonstrating features like the order of tissue development, and the cascade of chemical triggers we might see in a growing fetus.
By studying the progress of tissues with the mutated versions of TCF4 taken from individuals with Pitt Hopkins syndrome, and comparing them against tissues with more typical TCF4 genes, the researchers could map changes in the tissues' structure and operation.
"Even without a microscope, you could tell which brain organoid had the mutation," says pediatrician Alysson R. Muotri from UC San Diego.
The masses created with atypical TCF4 genes were noticeably smaller than the control organoids, for one thing, with some showing a polarized distortion in their general structure.
The researchers also discovered that the version of the gene responsible for Pitt Hopkins syndrome freezes the progenitor cells that give rise to different types of neuron, impairing their ability to diversify.
This results in a reduction in the amount of neurons in the cortex, as well as a drop in their activity – two factors that could help explain the more profound differences in brains with autism or schizophrenia.
Part of the cause of this drop in neural differentiation seems to be a drop in a specific type of signaling that occurs across cell membranes.
By artificially supporting this signal through targeted pharmaceuticals, the researchers found they could return at least some of the neural diversity and electrical activity to the cortical areas of the organoids.
Genetically correcting the TCF4 mutations in the tissues also reversed the mutation's effects, making the organoids constructed from volunteers with Pitt Hopkins syndrome look more similar to control organoids.
"The fact that we can correct this one gene and the entire neural system reestablishes itself, even at a functional level, is amazing," says Muotri.
It's a small key piece of information that could one day lead to some revolutionary therapies, though that day is still a long way off.
Organoids aren't fully functional brains, leaving plenty of room for overlooked factors that could complicate matters.
More importantly, conditions such as autism and schizophrenia only become evident after birth. Without knowing how changes in the differentiation and activity of nerves impact the function of a more fully-formed brain, it's impossible to know the value of therapies like these.
But while it's a small step towards understanding how some neurodevelopmental disorders unfold, it's also a breakthrough that could give those affected by the mutated gene a choice in how they manage their wellbeing.
"For these children and their loved ones, any improvements in motor-cognitive function and quality of life would be worth the try," says Muotri.
This research was published in Nature Communications
Amazing news.
Amazing news.
There might be hope for the left after all.
You may be more right than you think.
Much of the Left’s activities are very autistic in nature.............
If you study the autism literature for any length of time it becomes obvious that there are many “autisms” caused by different disrupted genes and undoubted environmental triggers.
Probably in the future “autism spectrum disorder” will be broken down by the causative factor. Much like a “headache” could be migraines, cancer, meningitis, etc.
Winner.....
There may be hope for Potato Head after all.
I have a grandson who is on the spectrum. I would love to think that someday he won’t have to deal with the limitations he has. He’s only six and he’s what used to be considered “high functioning”, so he’ll probably do fine ultimately. But, I think life is going to be hard for him. On the other hand, life can be hard for all of us. I do my part to encourage him and I make sure he knows he’s an awesome person.
Sounds great but 75% of autism is ultimately determined by epigenetics (environment including prenatal).
I have a grandson who is on the spectrum, as well.
He is now 12 and doing fine in school, with proper medication.............
Like what? What environmental factors? My daughter has “high functioning autism”. She is an adult, a college graduate. She didn’t have anything in her environment that I can point to as causing autism.. Especially I wonder because many families, like ours, have non-autistic children along with the autistic one. The environment for all the siblings is pretty similar.
I think you are right. There’s a lot of variety, and they keep recategorizing. Like apparently no one uses the term “Asperger’s” now, although it was common a few years ago.
Psychologist said my kid is an Aspie, that’s why I did so much research on the subject.
She wakes up, starts doing math problems at 6:30 in the morning and doesn’t stop until I put her to bed.
Wow. My husband grew up doing math problems for fun. It led to a long happy career in aerospace. He says a good portion of his co-workers are likely on the spectrum but were never diagnosed.
I’m very high functioning on 5he spectrum, but can’t drive.
My kid had a toddler electric car and could never drive it, but she’s doing long division in her head. She’s not in grade school yet. You all can do some amazing things.
You are just wonderful, Ma’am, to your grandson. Thank you very much for lending him so much support, morally and otherwise.
It also gladdens my heart to see so much research being done on the subject of autism. Maybe in the future there will be even more medical help available to patients.
I think that is one of the few instances where there has been real progress in recent years.
When I was young, hardly anybody knew much about it (I was not diagnosed until I had turned forty) - and this even went for professionals.
May your grandson, and Mr. Red Badger’s grandson too, ultimately have an easier life that other people on the autistic spectrum had in the past. Your loving support will mean the world to them, I am sure.
God bless you.
I didn't realize there are meds for people with ASD. What does your grandson take and what does it do?
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