NATURAL HISTORY STUDY ONGOING
Care4ASH1L in collaboration with Brown University has initiated work on creating a Natural History Study to encapsulate the disease related information from ASH1L families. The data collected would help identify and stratify the phenotypes associated with ASH1L, leverage research in the optimal direction and ensure clinical trial readiness.
COST : None
VORINOSTAT - THE NEW HOPE FOR ASH1L
Researchers Dr. Jin He and his team from Michigan State University used Ash1L-deletion-induced ASD/ID mouse model and showed that postnatal administration of vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), significantly ameliorated both ASD-like behaviors and ID-like cognitive memory deficit.
SAHA is a pan-HDACs inhibitor approved by the U.S. Food and Drug Administration (FDA) to treat human cutaneous T-cell lymphoma (CTCL). Researchers used a low dose of SAHA (5 mg/kg/day) in this study. The low dose of SAHA used in this study is well tolerated and has low toxicity to mice. However, its safety and efficacy in treating human patients merit further investigation.
In summary, their current study provides experimental evidence to show that the postnatal administration of low-dose SAHA significantly ameliorates the sociability, repetitive behaviors, and cognitive memory in the Ash1L-deletion-induced ASD/ID mouse model, indicating that SAHA is a promising reagent for the pharmacological treatment of core ASD/ID behavioral and memory deficits caused by disruptive ASH1L mutations.
Postnatal administration of vorinostat (SAHA) ameliorates the core ASD-like behaviors in the Ash1L-deletion-induced ASD/ID mouse model.
Postnatal administration of vorinostat (SAHA) ameliorates the cognitive memory in the Ash1L-deletion-induced ASD/ID mouse model.
Different behavioral deficits have distinct responses to vorinostat (SAHA) treatment.
No obvious drug toxicity was observed during low-dose vorinostat (SAHA) treatment.
Here the researchers show loss of ASH1L in the developing mouse brain is sufficient to cause multiple developmental defects, core autistic-like behaviors, and impaired cognitive memory. This study establishes an ASD/ID mouse model (Ash1L knockout mouse model) revealing the critical function of an epigenetic factor ASH1L in normal brain development, a causality between Ash1L mutations and ASD/ID-like behaviors in mice, and potential molecular mechanisms linking Ash1L mutations to brain functional abnormalities. The study includes:
Generation and characterization of Ash1L knockout mice
Loss of ASH1L delays embryonic and postnatal brain development
Loss of ASH1L in the developing mouse brain causes ASD/ID like behaviors
Loss of ASH1L impairs expression of genes critical for brain development