From Feb 13th, 2017 news release:

"Findings on Facioscapulohumeral Muscular Dystrophy

FSHD is a debilitating disease that arises from a genetic defect and is one of the most common types of muscular dystrophy affecting approximately 12 in 100,000 people. This muscle disorder initially affects the muscles of the face, shoulder blades and upper arms with eventual spread to other muscles of the body.

In research conducted at Saint Louis University and subsequently used in a patent application, BET inhibitors were shown to inhibit expression of the DUX4 gene, which is expected to reduce the severity of symptoms in this disease. Apabetalone treatment, when compared to other BET inhibitors, demonstrated a similar repression of DUX4, however no transient suppression of MYH2 (a differentiation marker for myotubes) was observed. This differential effect on the marker of muscle cell differentiation was unique to apabetalone and demonstrated the distinct properties of this BET inhibitor.

Treatment of FSHD via BET protein inhibition offers a novel therapeutic indication for apabetalone and this class of compounds."

The above news release is in response to a paper by Francis Sverdrup and colleagues from Saint Louis University entitled "BET bromodomain inhibitors and agonists of the beta-2 adrenergic receptor identified in screens for compounds that inhibit DUX4 expression in FSHD muscle cells."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584331/

I noticed recently that the FSHD program is now listed on the Resverlogix clinical webpage. This is interesting since the only other clinical programs listed, other than BETonMACE, are those for CKD, PAH, Fabry's and Vascular Cognitive Dementia, all of which are ready to go with Phase 2 trials. In that FSHD section it now states: "Apabetalone has been shown to inhibit the expression of DUX4, the protein identified as the primary cause of FSHD, in human skeletal muscle cells. Strategic partnerships are currently being pursued to support testing apabetalone in FSHD animal models. At the same time, development of a topically-administered formulation of apabetalone is in progress, to improve muscle-specific delivery of the drug." [my bolding added]. Is the fact that this FSHD program is now listed on the clinical page a sign that the Resverlogix team is close, if not ready, to test a topical formulation in human clinical trials?

Also, thanks to rndtbl for posting the updated patent filed by Francis Sverdrup of Saint Louis University that states: "While pulse treatment with most BETi allows recovery of the lineage-specific MYH2 gene expression in myotubes, it is surprising that the BETi RVX-208 did not suppress MYH2 expression upon continuous exposure. FIGS. 17A and 17B demonstrate that 20 μM RVX-208 does not reduce MYH2 expression while significantly reducing DUX4 target gene expression. RVX-208 is different than other known BETi in that it preferentially binds the second of the two bromodomains present in BET proteins (BD2). The functional consequence is that fewer genes are affected by RVX-208. We have shown by two methods (pulse exposure-recovery with inhibitors such as I-BET762 and (+)-JQ1 and continuous exposure to the unique pharmacophore RVX-208) that blocking DUX4 expression via BET inhibition can be achieved without significant unwanted effects on muscle cell differentiation."

So sounds like the Resverlogix team is working on a potential topical formulation. Perhaps oral administration of apabetalone doesn't get much to the muscles. Very cool that BD-2 selective inhibition by apabetalone elicits the effect on DUX4 with continuous drug exposure without affecteing MYH2. If they succeed in developing an effective topical formulation for FSHD, I wonder what other conditions this topical formulation may be amendable to? 

BearDownAZ