The majority of therapeutic approaches currently in clinical development for SMA, aim to increase the levels of the SMN protein, either through the back-up gene, SMN2, or through the replacement of the missing gene, SMN1. There is therefore a need for sensitive methods to quantify increases in SMN protein in blood and other accessible tissues.
Phillip Zaworski of PharmOptima LLC and Katharine von Herrmann of the SMA Foundation, along with their team, have found a new method, an assay, to detect levels of SMN protein in the blood. Using the assay, they measured SMN protein in whole blood from SMA patients and healthy controls and found that SMN protein levels were associated with SMN2 copy number and were greater in SMA patients with 4 copies, relative to those with 2 and 3 copies. SMN protein levels did not vary significantly in healthy individuals over a four-week period and were not affected by circadian rhythms. Almost half of the SMN protein was found in platelets, components of the blood involved with clotting and healing. The team also showed that SMN protein levels in mice with a mild form of SMA, were high in the neonatal stage, decreased in the first few weeks after birth and then remained stable throughout the adult stage. Importantly, SMN protein levels in the CNS correlated with SMN levels measured in whole blood of these mice. These findings have implications for the measurement of SMN protein induction in whole blood in response to SMN-upregulating therapy.
Phillip Zaworski of PharmOptima LLC and Katharine von Herrmann of the SMA Foundation, along with their team, have found a new method, an assay, to detect levels of SMN protein in the blood. Using the assay, they measured SMN protein in whole blood from SMA patients and healthy controls and found that SMN protein levels were associated with SMN2 copy number and were greater in SMA patients with 4 copies, relative to those with 2 and 3 copies. SMN protein levels did not vary significantly in healthy individuals over a four-week period and were not affected by circadian rhythms. Almost half of the SMN protein was found in platelets, components of the blood involved with clotting and healing. The team also showed that SMN protein levels in mice with a mild form of SMA, were high in the neonatal stage, decreased in the first few weeks after birth and then remained stable throughout the adult stage. Importantly, SMN protein levels in the CNS correlated with SMN levels measured in whole blood of these mice. These findings have implications for the measurement of SMN protein induction in whole blood in response to SMN-upregulating therapy.
http://www.smatrust.org/smn-protein-in-blood-can-be-measured-implications-for-clinical-trials/
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