Healthcare (Commonwealth Union) – A novel cancer medication might improve cognitive function for individuals with Rett syndrome, a rare autism-related disorder, according to recent research from the University of California San Diego. This breakthrough could pave the way for new treatments for other neurological conditions.
The study, appearing recently in Stem Cell Reports, emphasizes the importance of microglia — a type of white blood cell in the central nervous system — in brain development.
Although these cells are well-studied in neurodegenerative diseases like Alzheimer’s, amyotrophic lateral sclerosis (ALS), and multiple sclerosis, their role in early neural development has remained largely unknown due to limited access to fetal tissue, explained Dr. Pinar Mesci, the study’s lead author. Mesci conducted the research at the University of California San Diego before moving to a new position.
To investigate further, Mesci utilized brain organoids — essentially “mini brains” that replicate the embryonic brain’s development — derived from the skin stem cells of consenting patients. These organoids were developed from both individuals with Rett syndrome — a condition mostly affecting females, characterized by the loss of speech, purposeful hand use, mobility, and muscle tone, among other symptoms — and neurotypical individuals.
When Mesci introduced healthy microglia to the Rett syndrome brain organoids, she observed an improvement in synapse function, where neurons connect and communicate. This improvement was due to the restoration of phagocytosis, a process by which microglia — often described as the central nervous system’s “janitors” — engulf and eliminate foreign substances like bacteria and dead cells, maintaining cleanliness in the brain and spinal cord. Phagocytosis also includes the pruning of synapses, which enhances brain efficiency.
Researchers also discovered that the synapses of normal neurons showed impaired functionality when microglia from Rett syndrome were introduced, giving further confirmation to the importance of these immune cells in brain function and development.
Alysson Muotri, Ph.D., a professor at UC San Diego School of Medicine, and the senior author and director of the Integrated Space Stem Cell Orbital Research Center at the university’s Sanford Stem Cell Institute indicated that when the brain’s ‘janitors’ are not performing their duties, problems begin to emerge.
Faulty microglia make cognitive tasks even more challenging for Rett syndrome patients, who already struggle with fewer and impaired synapses and dysfunctional astrocytes due to the loss of function in the MECP2 gene, which have been linked to other neurodevelopmental disorders as well.
Muotri indicated that microglia lacking proper MECP2 function are not as effective at pruning synapses and shaping the neural network and pointed out that they do not perform well.
The team subsequently evaluated a series of existing drugs on microglia to determine if any could restore phagocytosis. They discovered one: ADH-503, also known as GB1275. This experimental oral medication for pancreatic cancer also reduces the number of immune-suppressing cells that infiltrate a tumor. The drug acts as a regulator of CD11b, a protein involved in phagocytosis and other processes.
Other research on Rett syndrome has pinpointed potential therapeutic targets. However, none have yet identified a possible treatment involving human microglial cells.
By the time Rett syndrome patients are diagnosed, it is too late to repair and currently impossible to replace faulty neurons, the disease’s primary issue. Mesci indicated however that by concentrating on other cell types and potentially finding drugs that enhance their function, they might improve the environment for those neurons and ease functioning for patients and she indicated that it was what excited her.
Many other researchers have also focused on diagnosing autism earlier as possible as the possibility of an earlier diagnosis has often been beneficial in some cases in the treatment of various diseases.
“I hope this work will ‘move the needle’ and bring the Rett community back to neuroimmunology,” says Kipnis. “Understanding neuro-immune interactions in this complex disease may not only provide new insights into the disease biology, but also develop novel approaches to attenuate its progression.”
A cancer drug for some with autism who have the condition Rett syndrome, where the Rett syndrome patients may benefit is a positive development. Further research into exactly how the action of the drug can be improved and avoiding any possible side effects could advance this treatment. Rett syndrome, cancer drug, cancer drug for some with autism, Rett syndrome patients
