Originally published on August 15, 2013.
The grant award to Dr. Krainer’s lab is the fourth drug discovery project funded by Cure SMA in 2013 with a total investment of $550,000. This program will systematically assess the effect of backbone chemistry on the therapeutic efficacy of Antisense Oligonucleotides (ASO) that target the ISS-N1 region of the SMN2 RNA. ASOs that bind to the ISS-N1 region will be compared. This is the binding region of the drug ISIS-SMNRx that is currently being tested by Isis Pharmaceuticals in SMA clinical trials. This funding is being awarded to both Dr. Yimin Hua and Dr. Adrian Krainer at Cold Spring Harbor Laboratory. Both scientists are long-term collaborators with Isis Pharmaceuticals and actively participated in the pre-clinical development and characterization of the mechanism of action of ISIS-SMNRx.
Meet Dr. Krainer:
Who are you?
I have been working on RNA splicing mechanisms for 30 years. My lab also studies the role of defective splicing in genetic diseases and cancer, with a focus on development of targeted therapies based on splicing mechanisms.
How did you first become involved with SMA research?
I attended an SMA workshop at the NIH around 1999. It was reported then that the SMN2 gene has a splicing defect due to a mutation in exon 7. We had been studying a mutation in exon 18 of the BRCA1 gene that caused skipping of that exon, and that got me interested in pursuing the underlying mechanisms, which later led us to developing methods for correcting defective splicing.
What is your current role in SMA research?
My lab collaborated with Isis Pharmaceuticals to develop andcharacterize the mechanism of action of a novel antisense drug, ISIS-SMNRx. We continue to study this type of compound, both to help in its development as a therapeutic, and to obtain insights into SMA disease mechanisms using mouse models.