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Abstract Details

The Transplantation of a Specific iPSC-Derived Neural Stem Cells Subpopulation Improves the Pathological Hallmarks of Spinal Muscular Atrophy with Respiratory Distress Type 1 in Mice.
Neuromuscular and Clinical Neurophysiology (EMG)
S58 - Therapeutics in Neuromuscular Disorders (2:17 PM-2:28 PM)
008

Spinal muscular atrophy with respiratory distress type I (SMARD1) is an infantile autosomal recessive genetic disease, caused by mutations in the IGHMBP2 gene which cause the reduction of the ubiquitous protein IGHMBP2. SMARD1 is characterized by a progressive loss of motor neurons (MNs), leading to a muscular weakness and atrophy, and by a severe respiratory distress caused by diaphragm palsy. Currently, there are no effective therapies for this disease.

 

Evaluate the therapeutic effect of iPSC-derived neural stem cells on the neuropathological hallmarks of SMARD1 disease.


We generated NSCs from pluripotent stem cells (iPSCs) of healthy controls then selected for the expression of the specific molecules LewisX, CXCR4 and β1-integrin. We administered intrathecally the NSCs selected into SMARD1 mice (nmd) at postnatal day 1 after a previous evaluation in NOD-SCID mice. We verified the properly migration of LeX+CXCR4+β1+ NSCs from the central nervous system and the engraftment in the spinal cord parenchyma.

To evaluate the beneficial role of the treatment we studied the overall appearance of nmd mice and the effect on muscles, neuromuscular junctions (NMJ) and MNs.


The transplanted LeX+CXCR4+β1 NSCs engrafted in the spinal cord of nmd mice with a significant improvement in the phenotypic hallmarks of the disease.

Treated nmd mice showed ameliorate overall appearance, recovery of neuromuscular functions and increase in lifespan. The NSC subpopulation protected endogenous MNs from degeneration and it also had a beneficial effect at the periphery, promoting NMJ maintenance. Moreover, the specific treatment positively affected muscular tissues, that presented an ameliorated muscle fiber morphology and organization and less fatty infiltration.


Overall, we demonstrated that transplantation of a specific human iPSC-derived NSC subpopulation, selected to enhance migration, survival and engraftment, has a beneficial role in modifying the course of SMARD1 pathology supporting NSC-mediated therapy.


Authors/Disclosures
Stefania Corti, MD, PhD (Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico)
PRESENTER
Dr. Corti has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Corti has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Corti has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta.
No disclosure on file
Monica Nizzardo No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Nereo Bresolin, DR No disclosure on file
Giacomo Comi Giacomo Comi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Giacomo Comi has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis.