"I think the question we should be asking is, do you believe in this thing or not?" We discuss the value of MRI-informed muscle biopsies compared with uninformed biopsies, how we go about interpreting FSHD clinical trial gene expression data, and after the song, we show the Jones Lab CRISPRi presentation from the ASGCT annual meeting in Boston.

"I'm not bad. I'm just drawn that way." Today we finish up some questions on clinical trials, therapeutics, what may be in the future, and other random FSHD topics. Good times :)

"Blue Horseshoe loves Anacott Steel." Today we cover recent clinical trial news in the FSHD space and delve a bit deeper into some topics from part 1 of our Reddit Q&A. **Updated version**

The lowlight was Roche canceling their trial. The highlight was Sarepta's announcement of preliminary clinical data. Getting siRNAs, ASOs, and viruses into liver is easy because liver is filled with leaky capillaries, however, muscle is poorly vascularized and blood vessels have tight junctions so targeting cell receptors for enhanced transcytosis greatly enhances skeletal muscle delivery. Sarepta's targeting of the alpha v beta 6 integrin is a great advance in delivery of siRNA against DUX4 and, as predicted, shows the best DUX4 knockdown we have seen so far.

"I am the eyes and ears of this institution, my friends." You asked, we (try to) answer your questions. Part 1 of 2.

There is no song in this version due to copyright issues causing it to be removed for some of our international listeners, otherwise, same as the original version.

"So, Mr Tipton, how could it take you five minutes to cook your grits when it takes the entire grit-eating world twenty minutes?" We discuss the initial Epicrispr Biotech press release pertaining to their EPI-321 phase 1/2 clinical trial and the big picture science behind the RESTEM phase 1/2 clinical trial in progress and the Scholar Rock upcoming phase 2 clinical trial.

"That's super frustrating. It just makes me wanna pick up whoever is standing closest to me and throw them through this window and out into the infinite abyss of nothingness!" Brad, our angry Dad, is back with some questions about clinical trials and muscle building.

"There's another old saying, Senator: Don't piss down my back and tell me it's raining." We know a lot of you don't have the time or interest in all the details so we packaged up the highlights of the gene therapy series, with some new information and evaluation, too, into one shorter (but not short enough, we know) episode.

"But did you bleed him? - Aesculapius says that bleeding is not a cure. It is only a way of proving that you are a physician at the expense of your patient." Finally, we discuss the EPI-321 epigenetic editing phase I/II clinical trial design and its potential for answering key questions necessary for going to phase III and for providing benefit to participants and patients.