A team of researchers from the University of Pittsburgh have identified the cause of a new neurological syndrome and a potential therapeutic target for its treatment.
Description
RNA-binding proteins (RBPs) play a crucial role in regulating all steps of gene expression. Dysfunction of these proteins is linked to a wide variety of diseases, particularly neurological conditions. GEMIN5 is an RBP essential for assembly of the survival motor neuron (SMN) protein complex. The team have identified mutations on key domains of GEMIN5 in patients with neurodevelopmental delays. These mutations have been shown to disrupt the formation and assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of spliceosome formation leading to a neurological syndrome.
Applications
• Neurological conditions
• Neurodevelopmental disorders
• Motor neuron diseases including amyotrophic lateral sclerosis (ALS)
• Spinal muscular atrophy
• Ataxia syndrome
Advantages
The treatment of neurodevelopmental and neurological conditions remains a global unmet need for many patients. This novel approach could allow for identification of patients carrying specific mutations responsible for neurological dysfunction and facilitate more direct treatment of the underlying cause of a condition and other symptoms through genetic therapies.
Invention Readiness
In vivo data has shown administration of gene therapy increasing SMN can mitigate the neurotoxicity from mutations of GEMIN5. Biallelic variants in the gene GEMIN5 have been linked to a neurological syndrome with features of developmental delay, cerebellar atrophy and predominant motor dysfunction along with hypotonia. This has been confirmed in GEMIN5 knock down studies.
Studies have show genetic upregulation of SMN significantly increased the levels of GEMIN5 expression in cells and can suppress GEMN5-mediated toxicity. This SMN-mediated upregulation of GEMIN5 could provide a potential pathway for treatment of these neuropathologies.
IP Status
https://patents.google.com/patent/WO2024138018A1
