Matthew W Mosconi
University of Kansas, KS·Neuroscience
Some people who carry a mild expansion in a single gene develop a movement disorder later in life, with tremor and loss of balance that steadily worsens. The condition is Fragile X-associated tremor/ataxia syndrome (FXTAS), thought to be the most common single-gene cause of ataxia, meaning poor movement coordination, in older adults.
- Fields
Neuroscience
Genetics
Medicine & Clinical Research
- Topics
Fragile X-associated tremor/ataxia syndrome
FMR1 premutation
neurodegeneration
- Grants
- 1 known grant, through Nov 2028
What they work on
- Test whether premutation carriers with FXTAS show greater motor variability in hand control, postural control and gait, alongside reduced visual cortex–cerebellar Crus I functional connectivity on task-based fMRI, compared with carriers without FXTAS and healthy controls.
- Test whether sensorimotor deficits and reduced visual cortex–Crus I connectivity worsen over 24 months in FXTAS, and whether this decline is more severe in male premutation carriers.
- Use structural and diffusion MRI to test whether FXTAS patients have reduced cerebellar volumes and degraded microstructure in the cerebellum's main input and output pathways relative to carriers without FXTAS and controls.
- Test whether cerebellar volume and microstructure decline more steeply over 24 months in FXTAS, with attention to differences between male and female carriers.
- Examine how FMR1 gene measures (CGG repeat length, mRNA level, repeat instability) and ApoE allelic variants relate to the quantitative brain and sensorimotor markers, both cross-sectionally and across the two-year follow-up.
More about the research
It has no effective treatment. A core obstacle is measurement: there are no objective, quantitative markers of how the brain and behavior change as the disease advances, so researchers cannot link genetic and molecular causes to the degeneration itself.
Why it matters
FXTAS causes severe loss of motor function and quality of life in aging premutation carriers, and no treatments exist. Objective measures of cerebellar structure, brain connectivity and movement control could give clinicians and trials a way to detect FXTAS onset, track how fast it progresses, and judge whether a treatment is helping. Linking these markers to FMR1 and ApoE variation may also point to the biological pathways driving the disease and clarify why risk differs between men and women.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Caroline Dias
University of Colorado Denver/Anschutz Medical Campus, CO·Genetics
Profile cell-type-specific gene expression in post-mortem brain tissue from individuals with Fragile X syndrome, using single-cell sequencing.
Richard Ivry
University of California-Berkeley, CA·Neuroscience
Test the CoRT hypothesis, that the cerebellum continuously transforms internal representations, by comparing people with spinocerebellar ataxia to healthy participants on motor, perceptual and social judgment tasks.
Zheng Wang
University of Florida, FL·Neuroscience
Quantify verbal memory retention and executive function impairments in autistic adults aged 40–65 compared with age- and sex-matched cognitively normal controls, as early signs of dementia.
The school
University of Kansas: 26 labs on PI Pages, $546M a year on research, 351 research doctorates a year.
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