Radically different
A University of California, Riverside-led research team has developed a gene therapy that restored production of a missing brain protein, corrected abnormalities in brain circuitry, and improved behavior in a mouse model of Fragile X syndrome (FXS). The study, published in the journal Molecular Therapy Nucleic Acids, tested an adeno-associated virus (AAV)-based therapy carrying a normal human version of the FMR1 gene to produce the Fragile X messenger ribonucleoprotein (FMRP) and found that early treatment normalized several measures of brain activity while improving social behavior, exploratory behavior, and cognitive flexibility.
“In a typical brain, FMRP acts like a brake or a volume control,” said senior author Iryna Ethell, PhD, a professor of biomedical sciences at the UC Riverside School of Medicine. “Without it, neural circuits become overactive and less efficient, which contributes to many of the developmental and behavioral challenges associated with FXS.”
FXS is the most common single-gene cause of autism spectrum disorder. According to the researchers, the disorder typically manifests from expansion of CGG repeats in the 5′ untranslated region of FMR1. The mutation causes methylation and silencing of the gene, leading to a major reduction or complete loss of FMRP, an RNA-binding protein that regulates numerous messenger RNAs involved in synapse formation, maturation, and function. Loss of the protein can lead to abnormal synaptic activity and increased cortical hyperexcitability.
FXS can produce sensory hypersensitivity, seizures, anxiety, intellectual disability, developmental delays, repetitive behaviors, and social communication difficulty. Current treatments for this syndrome don’t seek to cure it, rather they are aimed at managing the associated symptoms of anxiety, hyperactivity, irritability, aggression, depression, and seizures.
The therapy developed by the research team was designed to replace missing FMRP rather than repair the original mutation. To do this, the researchers used an AAV9 viral vector to deliver human FMR1 isoform 7, one of the most abundant forms of the protein found in the brain. The therapy was tested in newborn mice lacking FMRP via intracerebroventricular injections at either a low or high doses.
The work built on earlier research that explored the potential of AAV-mediated restoration of FMRP in rodent models. These prior studies used a range of viral serotypes, promoters, delivery routes, and FMRP isoforms and showed they could partially or completely correct specific biochemical, physiological, and behavioral abnormalities. The researchers noted that studies involving mouse and rat FMRP homologs had shown that restoring the protein could improve a range of Fragile X-related deficits.
The current study showed that high-dose treatment produced the strongest positive effects in the mouse models. Electroencephalography showed normalization of baseline gamma power, improvements in responses to sound, reduced background neural activity, and improved habituation to repeated auditory stimuli. The therapy also restored abnormal patterns of brain-wave coupling that have been associated with Fragile X-related dysfunction.
Behavioral testing showed that these improvements persisted into adulthood. Mice receiving the higher dose displayed normalized exploratory behavior, improved social preference, and better performance in probabilistic reversal learning, a measure of cognitive flexibility that requires adapting when previously rewarded behaviors stop producing rewards.
“Fragile X mice tend to persist with an old solution even after the rules change,” Ethell said. “After treatment, they became much better at adapting, performing similarly to mice with normal FMR1 function.”
The researchers noted that their work showed the importance of delivering at therapy for FXS early in its development. They said that widespread distribution of the potential new gene therapy throughout the brain was necessary to achieve a therapeutic benefit. There was a clear relationship between the proportion of neurons expressing the therapeutic gene and the degree of functional recovery, which indicated that restoring FMRP in a sufficient number of cortical cells is critical for correcting any behavioral deficits.
While a promising step, the investigators said that the work was a preclinical study and that future research will now focus on developing delivery methods that can of have broad distribution across the human brain. The team also believes their approach could have broader applications.
“Beyond FXS, the findings may provide a roadmap for treating other genetic neurodevelopmental disorders caused by the loss of a single critical protein,” Ethell said. “Our study shows it may be possible to restore function across complex brain networks by replacing a missing gene. That gives us reason to be optimistic about the future of genetic medicine.”
The post Gene Therapy Restores Brain Function and Behavior in Fragile X Syndrome appeared first on Inside Precision Medicine.
by Annabella Hagen, LCSW
When I met Marie, she shared how faith and her connection with a Higher Power had always been important in her life. Her parents taught her that faith could be an anchor during hard times.
But Marie also had a genetic predisposition to obsessive compulsive disorder (OCD). When doubts and fears began to take over, she slowly lost confidence that she could ever feel peace again. Without knowing it, the more she tried to reason with the thoughts, fight them, or seek reassurance, the stronger they became.
Her OCD changed themes as she grew up. The voice within whispered different fears at different times:
“You may hurt the kids you’re babysitting.”
“You caused your granny’s pneumonia because you didn’t wash your hands well enough.”
“Am I going blind?”
“Why do these ugly images come into my head in sacred places? I must stop them.”
She tried to “fix” her doubts. But the more she focused on them, the more they grew. They distracted her from what mattered most — including her relationship with her Higher Power. She blamed herself for not feeling close to God. She felt ashamed and spiritually broken.
Many people with OCD blame themselves for their unwanted thoughts. They panic.
“Why would I think this?”
“What does this say about me?”
“Am I a terrible person?”
No matter what Marie did, she could not find certainty. She could not get enough reassurance. She wished she could control her thoughts and feelings. Because she couldn’t, she became very hard on herself. Her self-compassion slowly disappeared.
But here is something important: every human being — whether they have OCD or not — experiences disturbing thoughts, images, or impulses at times. Research going back decades, including studies like Rachman and de Silva (1978), shows that intrusive thoughts are common in the general population.
The difference is not the content of the thoughts. The difference is how often they come, how intense they feel, and how much distress they cause.
When someone without OCD has a strange thought, they may feel uncomfortable and say, “That was weird,” and move on.
But someone with OCD feels a strong need to solve the doubt. They may analyze it, argue with it, pray repeatedly, seek reassurance, or try to push it away. Without realizing it, these efforts make the thoughts louder and more frequent. This is how the OCD cycle grows.
Understanding this can bring hope. It means the problem is not your faith. It is the pattern.
And the good news is that OCD is not only genetic or neurological. It is also behavioral. That means you can learn to respond differently!
Thoughts and feelings are like the weather. They come and go. When we fight them or try to control them, they often stay longer.
You can learn to let them be.
Through Exposure and Response Prevention (ERP), you can practice moving toward what matters most — your faith, your family, your values — even when doubt is present. Instead of trying to silence the thoughts, you can choose not to follow the urge to fix them.
The first step is awareness.
You may already notice the unwanted thoughts. But can you notice how you respond?
Ask yourself gently:
These small moments of awareness begin to weaken the cycle.
As you practice new responses, you can begin shaping new pathways in your brain. Slowly, you can move closer to the connection with your Higher Power that you have been longing for.
Thoughts come and go. What matters most is what you choose to do.
You can act in faith and trust your Higher Power, even when the OCD voice is loud. That voice feels powerful, but it is not your identity. It does not define your relationship with God.
Change takes time. It takes practice. But it is possible. And it is worth it!
And you can find your way back!
Remember, OCD may try to use your faith as a weapon, your faith is not the problem—the disorder is. OCD is a health condition that seeks certainty where faith invites trust.
If you find yourself in a cycle of “loud” thoughts and repetitive compulsions—like over-praying, seeking constant reassurance, or fearing you’ve lost your connection to the divine—know that healing is possible.
To help more individuals like Marie navigate these challenges, the International OCD Foundation has released a comprehensive new brochure specifically for people of faith.
Download the “OCD is Not What You Think It Is” Brochure here or visit the Faith & OCD Resource Page to find more specialized support and information.
The post When OCD Is Loud, Trust Your Higher Power appeared first on International OCD Foundation.
The prevalence of autism spectrum disorder (ASD) is roughly one in 36 people, with a male-to-female ratio of 4:1. The disorder is known to be influenced by multiple factors, both genetic (gene mutations and copy number variations) and environmental, such as infections during pregnancy. However, the role of immunity in genetic ASD remains unclear.
One area of interest lies in lymphocytes—cells that are known to shape neurodevelopment and behavior. But their roles in neurodevelopmental disorders are not well defined.
Now, new research shows that a subset of T cells—γδ T cells—can infiltrate the brain and contribute to changes in social behavior in a genetic mouse model that mimics behavioral features of ASD. Depleting these cells from the brain increased sociability, suggesting that targeting abnormal immune function during neurodevelopment may offer interventions for ASD.
This work is published in Science Immunology in the paper, “CXCL16-mediated recruitment of γδ T cells to the brain reduces sociability in mice.”
Infections during pregnancy can induce the release of interleukin-17A (IL-17A) from T helper 17 cells and γδ T cells. Prior research has linked this type of maternal immune activation to neurodevelopmental disorders, but there is a lack of evidence connecting IL-17A and social behaviors in genetic mouse models.
To investigate this further, a team of researchers from the Division of Allergy and Immunology in the Medical Institute of Bioregulation at Kyushu University, in Fukuoka, Japan, studied 15q11-13 duplication (15q dup) mice—a mouse model that mimics a chromosome duplication found in some humans with ASD. These mice also demonstrate reduced social interactions, behavioral inflexibility, and increased anxiety-like behaviors.
The team analyzed immune cell populations in the brains of the 15q dup mice. Their findings suggest an increase in γδ T cells in the developing brains when compared with wild-type mice.
Using single-cell RNA sequencing (scRNA-seq), the team uncovered that this was most likely due to microglia in the brain expressing the chemokine CXCL16, which promotes immune cell migration. CXCL16 was highly expressed in the brains of 15q dup mice and contributed to increased infiltration of γδ T cells.
In addition, experiments revealed that deleting IL-17A–producing γδ T cells or blocking them with antibodies after birth increased sociability and reduced anxiety-like behaviors in the 15q dup mice.
Taken together, the authors note that these findings suggest that “immune dysregulation contributes to social behavior deficits in 15q dup mice, consistent with observations in maternal immune activation models, and may represent a potential target for interventions for ASD-associated differences in social behavior.”
The post Brain-Infiltrating T Cells Linked to Social Deficits in Autism Mouse Model appeared first on GEN – Genetic Engineering and Biotechnology News.