By Elodie Vaz | Published on Avril 23, 2026
| 3 min read
Sanfilippo syndrome, a
common form of childhood dementia, is a rare genetic disease characterized by
progressive and fatal neurodegeneration. Affected children initially develop
normally before rapidly losing cognitive abilities, language, and motor skills.
Early clinical signs—hyperactivity, sleep disturbances, erratic
behavior—precede an inexorable decline. In Australia, around 1,400 children are
affected, and hundreds of thousands of cases are reported worldwide. Behind
these numbers are deeply disrupted family lives. “It’s like grieving the life
of your child before it has even begun,” said Tenille Koistinen, mother of an
affected child, in a press release.
Deciphering early
disease mechanisms
In the absence of
curative treatment, understanding early cellular mechanisms is a major
challenge. A study published on April 7 in Nature Communications,
conducted by an international collaboration led from Australia, aims precisely
to identify the initial alterations responsible for neurological decline. For
Professor Cedric Bardy, lead researcher and director of the Neurophysiology and
Human Genetics Laboratory at the South Australian Health and Medical Research
Institute (SAHMRI) and Flinders University, the goal was to move beyond the
view of a purely late-stage degeneration and instead explore dysfunctions
occurring at the earliest stages of brain development.
A stem cell–based
experimental approach
To achieve their
findings, researchers used cortical neurons derived from human stem cells
obtained from patients with Sanfilippo syndrome. These cellular models were
analyzed using advanced electrophysiological and molecular techniques, allowing
detailed observation of synaptic activity and neuronal network organization.
This in vitro approach made it possible to replicate stages of brain
development and identify emerging abnormalities as neurons matured.
Overactive synapses
from early development
The results reveal
chronic hyperactivity in neuronal circuits. “What we observe in these
children’s neurons is an increase in excitatory activity that disrupts the
brain’s natural balance,” explained Professor Bardy in a press release.
Initially functional, neurons gradually become hyperactive, generating bursts
of intense and synchronized electrical activity. This dynamic mirrors the
symptoms observed clinically.
“This hyperactivity
provides a clear biological explanation for early behavioral changes and brings
us closer to understanding the complex mechanisms underlying childhood
dementia.” Moreover, the study shows that these neurons are particularly
vulnerable to metabolic stress. Even a mild nutritional deficiency worsens
synaptic abnormalities, suggesting that environmental factors may accelerate
disease progression.
“Our research shows that
disrupted synaptic communication is not merely a byproduct of degeneration—it
is an early driver of the disease.” This shift in perspective positions
synapses as primary therapeutic targets.
Toward personalized
medicine for childhood dementia
These findings open major
new avenues. “This research is important not only for Sanfilippo syndrome but
for the field of childhood dementia as a whole,” said Megan Maack, CEO and
founder of the Childhood Dementia Initiative. By identifying precise cellular
mechanisms, researchers are now considering personalized medicine approaches.
Preclinical studies have
already shown that certain existing drugs can correct these synaptic
imbalances. “Encouragingly, we have already demonstrated in the lab that these
synaptic imbalances can be corrected,” noted Professor Bardy, pointing to a
tangible therapeutic target. The team now has “a new preclinical tool” to
evaluate such treatments.
Read next: Preventing
cognitive decline: the winning trio?
About the Author –
Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on
human life. A registered nurse since 2010, she spent twelve years at patients’
bedsides before exchanging her stethoscope for a notebook. She now investigates
the links between environment and health, convinced that the vitality of life
cannot be reduced to that of humans alone.
