Although still preclinical, these results demonstrate how SMN2
splicing modifiers could correct the molecular deficit that causes SMA, said Luca Santarelli, Head of Neuroscience, Ophthalmology and Rare Diseases at Roche.
A second closely related back-up gene called SMN2
exists that normally produces a truncated and low-functioning form of SMN protein.
DNA samples previously characterized for SMN1 and SMN2
copy numbers (homozygous SMN1 deletion, SMN1 deletion carriers, and normal with variant SMN1 and SMN2
copy numbers) were used as controls.
Singh has discovered a way of using SMN2
to produce the working SMN protein.
8220;We are very grateful to Families of SMA for funding our ASO project as we hope we can continue to develop therapeutics that target an additional genetic element within SMN2
Because of the alternative splicing, SMN2
does not compensate for the homozygous loss of SMN1.
Results from the first cohort that included 13 adult and adolescent SMA patients demonstrated that SMN protein can be increased with RG7800, providing proof of mechanism for oral small molecule SMN2
Currently there are six drug strategies being advanced for SMA: a) Small molecule SMN enhancers, b) Neuroprotectants, c) ASOs to correct SMN2
splicing, d) Stem cell therapy, e) Gene therapy, and f) Regulators of muscle function.
Quantitative analysis of SMN1 and SMN2
genes based on DHPLC: a highly efficient and reliable carrier-screening test.
Patients lacking a functional SMN1 gene survive only because humans carry a second gene called SMN2
which produces low levels of SMN protein.
RG7800 was well tolerated and preliminary review of the blinded data indicated substantial increases in full length SMN2
The researchers are using a mild SMA mouse that carries the human SMN2
gene and is also inducible.