Corinn Cross, MD (Host): Duchenne muscular dystrophy, or DMD, is a genetic disorder characterized by the progressive loss of muscle. It is a multi system condition affecting many parts of the body, which results in a deterioration of the skeletal, heart, and lung muscles. The estimated life expectancy for patients living with DMD ranges between late 20s and early 30s.

 This is Pediatric Insights, Advances and Innovation in Children's Health, where we explore the latest in pediatric care and research. I'm your host, Dr. Cori Cross. Today we have with us Dr. Kaitlin Batley, Pediatric Neurologist at Children's Health and Assistant Professor at UT Southwestern. She is here to discuss how Children's Health is working on improving care and increasing the life expectancy for patients living with DMD.

Welcome, Dr. Batley. Thank you for being here with us today.

Kaitlin Batley, MD: Thank you so much. I'm thrilled to be here.

Host: So let's jump right in. Can you give us a brief understanding of Duchenne muscular dystrophy, what causes it, and how it affects the body?

Kaitlin Batley, MD: So DMD is an inherited muscle disorder. It is due to a pathogenic variant or genetic mutation in the DMD gene, which creates a protein called dystrophin. Without the dystrophin protein, the stability of the muscle is impaired and so that leads to progressive breakdown and degeneration of muscles.

With time, these muscles lose the ability to regenerate or repair themselves and progressive weakness is seen. We usually see symptom onset anywhere from kind of toddlerhood to school age children. Usually beginning with proximal muscle weakness, so difficulty with things like climbing up stairs or standing up from the ground or keeping up with other kids their age.

Usually that triggers referral to a neurologist or geneticist and the diagnosis kind of proceeds after genetic testing from there.

Host: And this is not part of our prenatal screening.

Kaitlin Batley, MD: Correct. It has been added to newborn screening in three states as of right now. Texas does not currently have it on its newborn screen and it's not yet on the recommended uniform screening panel or RUSP, although there are plans to propose that. And so this is not something that would be picked up with any kind of routine testing that's currently done.

Host: And lastly, it's more common in boys, correct, because it's X linked?

Kaitlin Batley, MD: Correct. It is an X linked disorder, and so it primarily affects boys, although there are reports of girls or carrier moms who have symptoms of DMD and who can be affected. It's much more common in boys, and we do see it in about 1 in 3500 to 1 in 5000 boys. So it's actually the most common muscular dystrophy.

Host: So tell us about the neurology team at Children's Health and the research partners at UT Southwestern who specialize in DMD care. How does their, or your really, expertise in this area influence the care and treatment options available for your patients?

Kaitlin Batley, MD: Our team at Children's Health is very devoted to the care of all of our boys with DMD. We're very fortunate to have a multidisciplinary team who kind of partners together to make sure that we're providing the optimal standard of care. We see our patients in a one day clinic where we have the cardiologist, pulmonologist, we have our physical and occupational therapist, and then depending on the other needs, a dietician or genetic counselor.

And so we've really got a very robust team who is very passionate about these families and treating this disorder. And in doing so, we stay up to date on current guidelines and try to provide the absolute best that we can.

Host: Now, speaking of staying up to date, I understand that in June 2023, the FDA recently approved a new drug called Elevidys? Can you tell us a little bit about this medication, how it works, the risks and benefits, and if this is something being offered at Children's Health?

Kaitlin Batley, MD: Elevidys is a gene transfer therapy. And so what it is, I call it an instruction manual or transgene to make a shortened dystrophin protein, which is then packaged into a viral vector. In this case, the particular virus is a form of adeno associated virus, and so the virus itself doesn't cause any disease in humans, but it is designed to take this transgene or this genetic material and deliver it to parts of the body that need this information so that way the body can start making an improved dystrophin protein. And so this medication is brand new and something that we have already administered here at Children's Health as one of the qualified centers to deliver such a therapy. And it really is a big step in progress moving forward in the treatment of DMD.

We do know that these treatments, medications, they can come with significant risks. And so whenever we talk about these medicines with our families, it's a very long discussion, to really make sure that we discuss everything that needs to be said about pros and cons and potential risks. And because we know that these things can happen, we have a very well defined monitoring schedule that we follow that after administration of the drug, checking weekly labs, making sure that we're staying on top of any abnormalities that could indicate more of an underlying issue so that way, we can catch these things before they become clinically apparent and treat ahead of time.

But we're hopeful that with the use of this medication we are providing these boys with the ability to make a better dystrophin protein, which will thereby slow the course of this disease, help keep their muscles stronger for longer, and we're hoping really change the outlook for this disorder.

Host: Now, in reading about this, and preparing for this interview, I read that the FDA only approved it for children between the age of 4 and 5 that are still ambulatory. Is that still true?

Kaitlin Batley, MD: That is correct. The initial approval was based on an accelerated approval due to kind of the promise of this medication in the initial studies, as well as the neurodegenerative nature of this disease. And so the initial studies looked at boys who were four to seven years old.

So based on that first study, the FDA chose to move forward with an approval for just the younger boys, four and five. However, there have now been additional trials that have expanded the number of boys who've received the medication in research trials, as well as the ages of boys. And so, they are actually have submitted to the FDA for an expansion of this approval. And so we're waiting to hear back if that will happen.

Host: So that's very encouraging. What outcomes have you seen from patients who have received Elevidys.

Kaitlin Batley, MD: So for our patients who've received Elevidys, we've had our first dose given in October. So we're just about five months from that. And so this is still rather early to see the major benefits, but we know that our patients who have received it already are reporting better energy level, improved strength with things like walking up the stairs, able to play more, keep up with their peers.

And so we're very hopeful that this is just a sign of things to come and that with time we'll really see the trajectory of this disease change from one that used to lead to just progressive degeneration up to one where our boys are gaining motor skills and getting stronger throughout this time period instead.

Host: And are there other innovative treatments at Children's Health that you're using to improve symptoms or life expectancy?

Kaitlin Batley, MD: Definitely. So in part of our devotion and passion to the DMD community, we are very involved in progressing our research in this field. And so, not only have we been a part of the clinical trials for Elevidys, we are also expanding to consider other therapies as well. There was a new steroid alternative treatment that was just approved and we were a part of that trial as well.

And then also looking at different kinds of drugs to combat some of the degeneration of things like the heart muscle. And so there is still a lot of work to be done in this field and, we're thrilled to be a part of that.

Host: It's really amazing. As a pediatrician, this is one of the conditions where you really feel for these kids because it is just neurodegenerative. So to see these sort of breakthroughs where we're able to slow it down and maybe walk a little bit of that back with these recombinant gene therapies, it's just amazing.

In reading, I was interested in the fact that it seems like there's other medications coming down the pipeline that are also recombinant gene therapy. One of them was SRP 5051. I don't know if you're up to date on it, but I was wondering, if you could tell us a little bit more about what you see coming down the pipeline in this gene therapy.

Kaitlin Batley, MD: So that's actually an exon skipping medication, and so that medicine it targets the underlying specific pathogenic mutation to kind of skip over a portion of the gene in order to allow the transcription to continue. So it's not technically like a gene transfer therapy like Elevidys is, but there are other gene therapies that are being investigated by other companies as well.

And there are several others that are in progress. And so I'm very hopeful that with time and experience, we'll be able to really fine tune this kind of therapy and really make this kind of the best sort of product that we can.

Host: So, in wrapping this up, is there anything else you'd like to share with us, or would you like to do a little futuring as to where you see care for patients with DMD going in the future?

Kaitlin Batley, MD: I think it's really an exciting time for this field to be able to think about all of these future therapies and what we might be able to offer very soon. And I really do see that the field of DMD treatment will be individualized and personalized. This will be the kind of therapy plan where each patient is getting maybe a different combination of medicines to really target their main issue at the time and to really treat their disease as best we can.

So in the future, I'm hopeful that we'll have many, many tools in our toolbox and different ways that we can help. So that ultimately, we can take this from a disease, which previously was so devastating for our families and turn this into something that we can really manage and allow our kids to have a typical life and follow their dreams.

Host: That's just amazingly encouraging. Thank you so much, Dr. Batley, for taking the time to share your expertise with us today. This has been super educational. I really enjoyed speaking with you.

Kaitlin Batley, MD: Thank you so much. And thank you for letting me talk about something that's so important to me and near and dear to my heart.

Host: To learn more about Children's Health's Pediatric Neurology Department and their DMD program, or any of the numerous conditions they treat, visit childrens.com/neurology.

 Thank you so much for your time with us today and to our audience for listening to Pediatric Insights, advances and innovations with Children's Health, where we explore the latest in pediatric care and research. You can find more information at ChildrensHealth.com. And if you found this podcast helpful, please rate, review, and share this episode. And please follow Children's Health on your social channels.