Asthma Drug Improves ERT Efficacy in Pompe Disease

Dwight Koeberl, MD

Dwight Koeberl, MD, at Duke University describes the studies he is doing to test albuterol and clenbuterol as a means to improve enzyme replacement therapy efficacy in patients with Pompe disease. This interview was conducted during Duke University's Pompe Disease Patient Meeting held April 8, 2017.


We've been working to develop more effective treatments for Pompe disease over the past several years and our focus has been on the ability to improve the response to available treatment - which is the enzyme replacement therapy or ERT. And what we demonstrated in our laboratory experiments was a drug, particularly beta2 agonist drug like albuterol or clenbuterol, can improve the uptake of enzyme during ERT and actually have a beneficial effect in Pompe disease. 
We started with our mouse model for Pompe disease because their GAA gene has been mutated and we can treat the mice with the same ERT as patients received. In our experiments, we added the drug clenbuterol to ERT and we showed a really significant benefit in terms of both the muscle taking up the enzyme, the GAA and the glycogen dropping when we added the drug clenbuterol.
We did a clinical trial with albuterol and we have tested that in our mice and showed that it had similar effects to clenbuterol but maybe not quite as impressive but albuterol was available in the United States as a drug that we can prescribe. So with our first study, patients who were stable treated with ERT for several years, we added albuterol treatment and measured things like the six-minute walk test and it was impressive that everyone was able to walk further in the six-minute walk test after they were taking albuterol. We also were able to do a muscle biopsy to show that some of the effects in the muscle from the albuterol were beneficial as we predicted. 
We wanted to go further with testing our favored drug, clenbuterol, which seems to have good effects in our experiments but it's not available in the United States. We were able to apply to the FDA for an IND number or investigational new drug number and that allowed us to import clenbuterol from Europe. Our main goal was to study safety and we did find that the drug was safe for patients with pompe disease. The secondary point was to look at any benefit for efficacy and it turns out that clenbuterol was beneficial by several different measurements in the study. Patients walk further in the six-minute walk test, and their respiratory muscles were stronger so they had improved pulmonary function test results. Importantly in the muscle biopsy, their enzyme was higher and their glycogen was lower and we could attribute this to the clenbuterol treatment because they're already receiving ERT for several years. We're currently applying to the FDA for a grant to do another larger study to generate more data.
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