Filippo Maria Santorelli

Stereospecific GPG acylation by CLN8 drives BMP biosynthesis and its loss leads to Batten disease

This study identifies CLN8 as a stereospecific GPG acyltransferase critical for BMP biosynthesis, showing its loss causes Batten disease and that S,S-LPG supplementation can restore BMP and improve neurological symptoms.

A glucosylcholesterol-cytoskeleton axis links GBA2 loss-of-function to synaptic and mitochondrial pathology in Hereditary Spastic Paraplegia

This study identifies a GlcChol-RAC1-actin signaling axis linking GBA2 loss-of-function to synaptic and mitochondrial dysfunction in SPG46, with Rac1 inhibition rescuing disease phenotypes in a zebrafish model.

Pathological variants in HPDL cause collapse of the neuro-glial unit during human cortical maturation

This study investigates the effects of HPDL variants on cortical development, finding synaptic impairment, glial loss, and reactivation of developmental programs in HPDL-deficient cultures.

Translational lipidomics reveals BMP and its precursor LPG as biomarkers for CLN5 Batten disease

This study identifies BMP and LPG as biomarkers for CLN5 Batten disease using lipidomics, showing their depletion and elevation in disease models and patient samples.

CLN5 deficiency impairs glucose uptake in Batten disease

This study develops a zebrafish model of CLN5 deficiency, revealing impaired glucose metabolism as a novel feature of NCL.

HPDL is critical in human cortical development via regulation of mitochondrial functional properties

This study shows HPDL is essential for cortical development by regulating mitochondrial function and neurogenesis, with implications for SPG83 pathology and potential antioxidant therapies.

Targeted long-read RNA sequencing reveals the complexity of CLN3 transcription and the consequences of the most common 1-kb deletion in patients with juvenile CLN3 disease

The paper uses long-read RNA sequencing to analyze CLN3 transcription complexity and the impact of a common 1-kb deletion in juvenile CLN3 disease, revealing multiple transcripts and isoforms.

Decreasing ganglioside synthesis delays motor and cognitive symptom onset in Spg11 knockout mice

This study shows that reducing ganglioside synthesis delays motor and cognitive symptoms in Spg11 knockout mice and reduces axonal spheroids.

A human pan-genomic analysis reconfigures the genetic and epigenetic make up of facioscapulohumeral muscular dystrophy

This study uses pan-genomic data to analyze D4Z4 repeats and CpG methylation in FSHD, finding low methylation correlates with SMCHD1 variants but not clinical phenotypes.

Sacsin cotranslational degradation causes autosomal recessive spastic ataxia of Charlevoix-Saguenay

This study identifies cotranslational degradation of mutant sacsin as the cause of ARSACS, explaining the lack of genotype-phenotype correlation and suggesting sacsin levels should be included in diagnostic algorithms.