SMA Europe Call for Projects 2012
Nach Beurteilung durch externe Gutachter und den eigenen wissenschaftlichen Beirat fördert SMA Europe die folgenden Projekte:
Dr. Shingo Kariya, Columbia University, New York, USA
„Elucidate the molecular mechanism underlying maturation and remodeling defects of the neuromuscular system in SMA“
Spinal muscular atrophy (SMA), a neuromuscular disorder caused by a deficiency of the SMN protein, is characterized by progressive muscle weakness. Our data from SMA model mice suggests that SMA patients receiving an SMN-increasing therapy can reduce medication after reaching a certain age, although they need to increase their medication for recovery from muscle injury. In this proposal, we investigate the exact mechanism behind this phenomenon.
Dr. Martine Barkats, Institute of Myology, Paris, Frankreich
“Optimization of AAV9-SMN gene therapy for SMA”
We recently discovered that the AAV9 gene vector was able to mediate gene transfer to the brain and the spinal cord despite the presence of the blood brain barrier. We further showed that this strategy allowed the dramatic rescue of a mouse model of SMA (maximal survival of 260 days instead of 16 days) via SMN gene transfer to the spinal cord. The development of a clinical project based on this systemic scAAV9-SMN delivery is ongoing as a collaboration between the Institute of Myology and Genethon. We propose to pursue this research by optimizing the vector and its route of delivery in order to improve the therapeutic effect of this promising gene therapy approach for SMA.
Dr. Frédéric Allain, Eidgenössische Technische Hochschule Zürich, Schweiz
“In search of small molecules targeting protein-RNA complex: a novel approach against SMA”
We propose to solve by NMR the structures of one activator complex of SMN2 exon 7 inclusion involving the proteins Tra2-β1 and hnRNP G and one repressor complex involving the protein hnRNPA1. In parallel, these two complexes will be used to screen a drug library by differential scanning fluorimetry to find small molecules that either stabilize or destabilize these two complexes, respectively. The structures and the selected compound will then represent a strong basis toward finding a drug against SMA.