PTC Therapeutics Announces Data Showing Six-Minute Walk Test Consistently Measures Ambulatory Function In Patients With Duchenne Muscular Dystrophy
Explain the trial?
PTC therapeutics is currently in Phase 2b of a clinical trial with Duchenne boys. The drug’s name is PTC 124. PTC 124 works by overriding a disease mutation that creates a stop (nonsense mutation) in the middle of the gene. By overriding the stop, the gene is copied in its full length and the resulting protein though possibly somewhat misshapen can be functional. The targeted gene and protein in Duchenne is dystrophin. For an indepth interview with PTC therapeutics, go here… (find the link to the interview on the newsletter)
PTC 124 is also in trial for cystic fibrosis patients simultaneously. If PTC 124 is efficacious in treating boys with Duchenne who have a nonsense mutation leading to their disease, it should be applicable to kids and adults with CMD who have a nonsense mutation. For more information about phase 2b clinical trial…..
This part of the trial tested the 6 minute walk test as a marker for clinical outcome, ie, to see if this test would show that the drug is working.
What is the relevance to CMD?
If PTC 124 works for nonsense mutations, it should work to help alleviate disease in those individuals with CMD who have a nonsense mutation if it works in Duchenne.
The 6 minute walk test will not be applicable as a clinical outcome marker in many of the people we know with CMD as many individuals with CMD are non-ambulatory. However, this is the start of a quest for clinical outcome markers in muscular dystrophy.
Why are clinical outcome markers important?
Without clinical outcome markers that are objective, it is difficult to prove a drug works in a clinical trial. Currently there is no “clinical rule” in muscular dystrophy, a medical/scientific term that applies to a set of markers that have been validated in a disease to track response to therapy and intervention. There is no blood indicator or blood test currently that correlates well with response to treatment as CK (creatine kinase) is variable.
To assess drug response, most researchers rely on muscle function tests, even in the mouse model, to see if there is an increase in strength and muscle biopsy (invasive). These muscle function tests have to be performed by the same individual in a highly controlled manner in order to maintain consistency and reduce operator bias.
There is a great need for objective clinical outcome markers in muscular dystrophy. It can be extremely costly to identify the markers and then test them in each patient population to validate the markers in light of disease progression. An exciting part of this trial is that the pharmaceutical company, testing the drug, funded a mini trial within the trial to look at establishing a clinical outcome marker, i.e., the 6 min walk test.
For more information about the trial:
PTC Therapeutics, Inc. (PTC) announced promising findings in patients with Duchenne/Becker Muscular Dystrophy (DMD/BMD) at the 13th International World Muscle Society (WMS) Congress. Results from an observational study assessing the utility of the 6-minute walk test (6MWT) as a primary outcome measure in trials of treatment for DMD/BMD showed that the 6MWT clearly differentiates boys with DMD from healthy boys, especially when adjusted for age.