A new study has found that a drug previously used to treat high blood pressure could be beneficial for the treatment of oculopharyngeal muscular dystrophy (OPMD).
The drug – called guanabenz acetate – had previously been shown to enhance a cellular process called the unfolded protein response (UPR). The UPR deals with proteins that build up inside the cell because they aren’t the right shape. Too many protein clumps are damaging to cells and are associated with lots of diseases including diabetes, Parkinson’s, motor neuron disease and OPMD.
In this new study, researchers from the UK and France tested a brand of guanabenz acetate called Wytensin in a mouse model of OPMD. They found that this drug had successfully enhanced the UPR, and there were fewer and smaller protein clumps inside the mouse muscle. This led to an improvement in muscle strength and reduced muscle scarring (fibrosis).
Although these results are promising, Wytensin has recently been discontinued because of side effects related to sleepiness (lethargy). The researchers did observe similar side effects in the OPMD mice but this didn’t seem to affect their activity levels. Of course mice are very different to humans, so a clinical trial will need to be conducted to fully understand the potential of Wytensin for OPMD. It’s possible that researchers may instead look at developing a new version of guanabenz acetate that has less side effects than Wytensin.
The benefit of repurposing an existing drug is that it’s already been tested in people, so researchers have a good understanding of where the drug acts in the body and its side effects. This may reduce the time and costs associated with developing the drug for another condition.
The study was published in the scientific journal, Human Molecular Genetics.
Dr Alberto Malerba from Royal Holloway University, who was lead author of the study, said:
We think our findings are relevant as the genetic defect in OPMD affects many biological processes and some of them are still unclear. Here we found evidence suggesting that a structure inside the cell called the endoplasmic reticulum is under stress in OPMD.
Guanabenz acetate helps the endoplasmic reticulum to correctly shape proteins and we found that it is beneficial for the muscles in a mouse model of OPMD.
Our study suggests that strategies targeting the unfolded protein response (UPR) could be beneficial for OPMD and that guanabenz acetate or other more recent pharmacological agents – like new derivatives of Guanabenz with similar beneficial effects but less side effects – should be tested for the treatment of OPMD and other disorders associated with protein clumping in humans.