Dame Kay Davies, Dr. Lee’s Professor of Anatomy in the department of physiology, anatomy and genetics at the University of Oxford in the United Kingdom, was awarded an MDA research grant totaling $207,566 over a period of two years to conduct a drug screen for molecules that can increase levels of a protein called utrophin, which can be developed for clinical trials in Duchenne muscular dystrophy (DMD).
DMD is caused by a mutation that prevents formation of normal dystrophin protein. “Utrophin is very similar to the missing dystrophin protein,” Davies says, and it is unaffected in DMD. Increasing the amount of utrophin has been shown to be beneficial in a mouse model of DMD, indicating the potential for utrophin-increasing drugs in humans. Drugs may offer benefits that other treatment strategies don’t, she says, since they reach every muscle in the body (which has been a challenge for some other strategies), including the heart and the diaphragm.
Davies' drug development efforts (supported by a previous MDA research grant) already have led to an MDA-supported phase 1 safety trial of a compound called SMT C1100, and further trials are planned. At the same time, Davies wants to develop drugs that do the same job better. “We aim to develop ‘best in class’ drugs to follow on from this,” she says. “We have developed a new, more sensitive screening assay and have already found new hits [drug candidates] that work better than the original drug in tissue culture.” Those now will be tested in mouse models, and tinkered with to optimize their performance.
“We are at an exciting point in this research, and we are optimistic that we will be able to find a drug which will increase levels of utrophin to provide substantial clinical benefit,” Davies says.
Funding for this MDA grant began Feb. 1, 2013.