A chemical cousin of the common antibiotic tetracycline (PTK-SMA1) might be useful in treating spinal muscular atrophy (SMA), a currently incurable disease that is the leading genetic cause of death in infants. This is the finding of a research collaboration involving Adrian Krainer, Ph.D., of Cold Spring Harbor Laboratory (CSHL) and scientists from Paratek Pharmaceuticals and Rosalind Franklin University of Medicine and Science.
About SMA :
About SMA :
SMA is caused by mutations in a gene called Survival of Motor Neuron 1 (SMN1), resulting in a decrease in the levels of SMN protein in the motor neurons of the spinal cord -- the cells that control muscle activity. Without the protein, these neurons degenerate, and infants born with the mutations progressively lose the ability to move, swallow, and breathe. There are no approved therapies for the treatment of SMA.
Mode of action of PTK-SMA1 :
The new molecule boosts the levels of SMN protein in cells by fixing a mistake in a cellular processing mechanism called RNA splicing. The drug candidate targets the splicing of a gene called SMN2, which is essentially a back-up copy to the SMN1 gene that’s mutated beyond repair in SMA patients. SMN2 doesn’t compensate for the loss of SMN1, however, because it produces too little functional protein. Most of the protein that is produced is missing a single important piece, without which the protein rapidly degrades. The significance of this finding is in the fact that “PTK-SMA1 is the only small molecule known to specifically alter RNA splicing by directly and solely targeting the splicing reaction” . Other molecules that affect splicing also affect other cellular processes, thus diluting their potency, and potentially increasing the risk of side effects. PTK-SMA1 has the added advantage of being a derivative of tetracyclines, which are nontoxic and have demonstrated safety in humans...
Source : http://stm.sciencemag.org/content/1/5/5ra12.abstract.
Mode of action of PTK-SMA1 :
The new molecule boosts the levels of SMN protein in cells by fixing a mistake in a cellular processing mechanism called RNA splicing. The drug candidate targets the splicing of a gene called SMN2, which is essentially a back-up copy to the SMN1 gene that’s mutated beyond repair in SMA patients. SMN2 doesn’t compensate for the loss of SMN1, however, because it produces too little functional protein. Most of the protein that is produced is missing a single important piece, without which the protein rapidly degrades. The significance of this finding is in the fact that “PTK-SMA1 is the only small molecule known to specifically alter RNA splicing by directly and solely targeting the splicing reaction” . Other molecules that affect splicing also affect other cellular processes, thus diluting their potency, and potentially increasing the risk of side effects. PTK-SMA1 has the added advantage of being a derivative of tetracyclines, which are nontoxic and have demonstrated safety in humans...
Source : http://stm.sciencemag.org/content/1/5/5ra12.abstract.
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