Tackling the Cause
Decades of basic FSHD research have produced the broad consensus that FSHD is caused by the undue production of a protein called DUX4. Our single goal is to develop an FSHD therapy that restores DUX4 repression as much as possible.
How do we go about this? One way might be to rely on further basic research to produce clues for a therapy. However, finding such clues firstly requires unraveling the factors – which are likely to be numerous – that control repression of DUX4. Secondly, assumptions must be formulated and tested on how all or some of those factors might be modulated so as to restore repression of DUX4. Thirdly, if an assumption appears to be correct (a big if since many assumptions are likely to be falsified), compounds with the right modulating capacity must be generated and tested (presumably by companies rather than universities). Typically, this approach proceeds very slowly. Instead, we follow an alternative approach known as drug discovery.
The first objective of drug discovery is to find compounds that work. In contrast, finding compounds that work is the last objective of basic research. In the case of FSHD, compounds that work are compounds that repress the undue production of the DUX4 protein, thereby tackling the cause of the disease rather than only its symptoms. So this is our first objective: to discover compounds that repress DUX4 protein production in human FSHD-affected skeletal muscle.