CMT-SORD: From Discovery to Clinical Trials

This episode explores the rapid advancements in understanding and treating CMT SORD, highlighting community engagement and innovative research, particularly focusing on the potential of the drug Gavorstat. The scientific journey from gene discovery to clinical trial showcases the power of collaboration, emphasizing patient voices in shaping treatment success.

• Discussion on what CMT SORD is and its symptoms 
• Overview of the SORD gene’s role in the disease 
• Insights into the drug Gavorstat and its mechanism 
• Updates on clinical trial results for Gavorstat 
• The importance of community support and advocacy 
• The role of the Hereditary Neuropathy Foundation 
• Implications of CMT SORD advancements for other types 
• Shift towards patient-reported outcomes in research 
• Reflections on the future of CMT treatment strategies

Learn more about SORD and Inspire Clinical Trial

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Transcript

Speaker 1 0:00

Welcome to CMT Simplified, brought to you by the Hereditary Neuropathy Foundation. This podcast delivers bite-sized updates on the latest research and advancements in Charcot-Marie-Tooth disease, CMT. With episodes ranging from 10 to 20 minutes, we cut through the jargon to bring you clear, concise insights into breakthroughs, treatments and scientific discoveries shaping the future of CMT. Perfect for busy listeners. Cmt Simplified is your on-the-go resource for understanding complex information in a straightforward and approachable way. Stay informed, empowered and up-to-date. One short episode at a time.

Sharko 0:41

Welcome to our deep dive on CMT Sword.

Marie 0:45

Pronounced like sword.

Sharko 0:46

Exactly CMT-SORD, and we're going to be looking at how this disease went from gene discovery to a potential treatment in record time.

Marie 0:55

It's pretty amazing how fast this all happened it really is. And it's a story that offers a lot of hope for the entire CMT community. There's been a potential breakthrough with this new drug called AT007.

Sharko 1:08

Oh, absolutely, and we've got all the latest info straight from Applied Therapeutics and the Hereditary Neuropathy Foundation.

Marie 1:14

Yeah.

Sharko 1:15

So before we get into treatment, let's start with the basics. Okay, what is CMT sword and how does it actually affect people?

Marie 1:21

So CMT sword, like other types of CMT, is a condition that affects the peripheral nerves. These are the nerves that carry signals from your brain and spinal cord to the rest of your body.

Sharko 1:33

Right.

Marie 1:33

So things like your muscles and your sensory organs, and when these nerves are damaged, it can lead to a variety of symptoms.

Sharko 1:40

Like what kind of symptoms?

Marie 1:41

So you can have things like muscle weakness, foot drop, difficulty with balance and even pain and numbness in your hands and feet.

Sharko 1:50

So it's like the communication pathways are disrupted Exactly and that leads to all these different problems. Now you mentioned that CMK's sword is caused by a specific gene Right, the sordid gene.

Marie 2:02

Yeah.

Sharko 2:02

Can you explain how this gene actually leads to the development of the disease?

Marie 2:06

Okay. So think of it this way your cells have a sort of recycling system to break down a type of sugar called sorbitol, and the sordid gene provides the instructions for making an enzyme. That's really important in this recycling process. But when there's a mutation in a gene, the enzyme doesn't work properly.

Sharko 2:26

Oh, I see.

Marie 2:26

So the sorbitol starts to build up.

Sharko 2:28

Okay.

Marie 2:29

And it particularly builds up in the nerve cells, and over time that buildup becomes toxic.

Sharko 2:33

Wow, so it's like a cellular traffic jam.

Marie 2:36

Yeah, you could say that.

Sharko 2:37

The sorbitol can't get processed properly.

Marie 2:39

Exactly.

Sharko 2:40

And it starts causing damage to the nerves.

Marie 2:42

Right.

Sharko 2:43

So the discovery of the SORD gene as the cause of CMT SORD was relatively recent, wasn't it?

Marie 2:49

It was Like 2020.

Sharko 2:51

Yeah, which is amazing to me, considering that we're already talking about potential treatments. That's true. How did researchers move so quickly from gene discovery to developing a potential therapy?

Marie 3:02

Well, that's a really good question and it kind of highlights the importance of building on previous research.

Sharko 3:07

Okay.

Marie 3:07

Scientists had already been studying this enzyme, this whole pathway, for decades, really Even before they knew it was connected to CMT, wow. So when the S-O-R gene was finally identified, they were able to use all that existing knowledge to fast track the development of a therapy that specifically targets that pathway.

Sharko 3:27

So it's like they had a head start.

Marie 3:28

Exactly, they had a foundation to build on.

Sharko 3:30

And that therapy you're talking about is Gavorstat right.

Marie 3:33

Yeah, that's right.

Sharko 3:34

And it's currently being tested in a phase three clinical trial called Inspire. Yes, it's amazing to me that we're at this stage already, given how recently the S-RG was discovered. Yeah, it really is. Can you tell us a little bit more?

Marie 3:49

about Goverstat and how it actually works. Sure, so Goverstat is a type of drug called an aldose reductase inhibitor.

Sharko 3:55

Okay.

Marie 3:55

Now, aldose reductase is an enzyme that's involved in converting glucose.

Speaker 1 3:59

Which is sugar.

Marie 4:00

Right sugar into sorbitol.

Sharko 4:02

Okay.

Marie 4:02

So by inhibiting this enzyme, cavorostat essentially reduces the amount of sorbitol that's produced in the body.

Sharko 4:09

So it's like cutting off the problem at the source.

Marie 4:11

Exactly. You're preventing that toxic buildup of sorbitol from even happening.

Sharko 4:16

That's pretty neat.

Marie 4:17

It is a really clever approach.

Sharko 4:19

So it's not directly fixing the SRD gene mutation.

Marie 4:22

No.

Sharko 4:23

But it's targeting the downstream effects.

Marie 4:25

Right, it's managing the consequences of that mutation.

Sharko 4:29

So it's kind of like a workaround solution.

Marie 4:30

In a way, yes.

Sharko 4:32

But a very elegant one.

Marie 4:33

Yeah, it's a very targeted approach.

Sharko 4:35

Now you mentioned that Gavorstat is being tested in a clinical trial. Yeah, what have the results been like so far?

Marie 4:41

Well, the trial is still ongoing.

Sharko 4:43

Right.

Marie 4:43

But the interim results are very encouraging.

Sharko 4:46

That's great to hear.

Marie 4:47

They've shown a significant reduction in sorbitol levels in patients who are taking Govorostat.

Sharko 4:52

That's promising.

Marie 4:54

It's a good indication that the drug is actually doing what it's supposed to be doing.

Sharko 4:57

Yeah, preventing that buildup.

Marie 4:59

Exactly.

Sharko 4:59

So it's supposed to be doing, yeah, preventing that buildup, exactly so it's working on a biochemical level Now, while we're waiting for those long-term results from the trial, it's been really inspiring to see the CMT sword community coming together.

Marie 5:09

Yeah, it has.

Sharko 5:10

And really rallying around this research.

Marie 5:12

It's been amazing.

Sharko 5:13

I've seen so many patients sharing their stories online using the hashtag the real sword.

Marie 5:19

The real sword. Yeah, it's using the hashtag TheRealSword, therealsword.

Sharko 5:21

Yeah, it's amazing to see their resilience and their determination.

Marie 5:24

It's really heartwarming.

Sharko 5:25

It is.

Marie 5:29

To see how people are coming together to support each other and to raise awareness about this condition.

Sharko 5:32

And those videos. They provide a really powerful window into what it's like to live with CMT. They really highlight the human side of this research and remind us that behind all the data and the science, there are real people. Real people Whose lives are directly affected by these breakthroughs.

Marie 5:50

Absolutely.

Sharko 5:51

Now, speaking of community, the Hereditary Neuropathy Foundation, yes, has played a really crucial role in facilitating this research.

Marie 5:59

They have.

Sharko 6:00

They've connected researchers with patients and they've been supporting the INSPIRE trial.

Marie 6:04

It's a great example of how collaboration and patient advocacy can really accelerate progress in rare diseases. It really is.

Sharko 6:12

It takes a village Exactly, and it's heartwarming to see everyone coming together towards a common goal.

Marie 6:17

It is.

Sharko 6:18

Now, this progress with CMT. It has implications that extend far beyond just this one specific type of CMT right. Absolutely, and that's what I'm really eager to explore next.

Marie 6:28

Okay.

Sharko 6:28

But before we move on, are there any other key takeaways that you'd like to emphasize about the science behind CMT Sword or the development of Gavor's step I?

Marie 6:39

think the key message here is that this success story is a real beacon of hope for the entire CMT community and even beyond. Yeah, it demonstrates that rapid progress is possible, especially when we leverage existing knowledge and when we foster a collaborative research environment.

Sharko 6:56

Yeah, and it highlights the power of patient advocacy.

Marie 6:59

Absolutely.

Sharko 7:00

In driving research forward, definitely Okay. So with that foundation laid, let's move on to the broader impact of this research and what it could mean for the future of CMT treatment.

Marie 7:10

Sounds good. What's exciting is the success with CMT. It's not just limited to CMT Sword. This breakthrough could change how we approach other types of CMT.

Sharko 7:21

Yeah, that's what I find so fascinating. By targeting the sword gene and that sorbitol pathway, researchers have opened up this whole new avenue for exploration. Exactly Like could this approach be applied to other forms of CMT that involves similar metabolic problems?

Marie 7:36

Yeah, precisely, it's like we've discovered this new tool that we can use to address a whole bunch of different problems, and scientists are now looking at other subtypes of CMT kind of with fresh eyes and investigating whether targeting specific metabolic pathways could be a good treatment strategy for those as well.

Sharko 7:55

And that brings us to another crucial aspect of this whole story.

Marie 7:58

Okay.

Sharko 7:59

It's the power of the patient voice. Yes, you know CMT sorority. Patients haven't just been passive recipients of this research Right. They've been active participants, definitely Shaping the trial design, sharing their experiences to raise awareness Absolutely and inspire others.

Marie 8:15

The real sword hashtag that you mentioned earlier is a perfect example of that.

Sharko 8:19

It is, and it's a reminder that behind all the science, there are real people.

Marie 8:24

Real people.

Sharko 8:25

Whose lives are being directly affected by these discoveries?

Marie 8:28

Absolutely.

Sharko 8:29

Yeah, it's so important to remember that human element because it's easy to get caught up.

Marie 8:34

Yeah.

Sharko 8:34

In the technical details of mutations in clinical trial, right, but ultimately it's about improving the lives of people and families, of course who are affected by these conditions Right up. And that human perspective has also influenced the way that clinical outcomes are even being measured in the INSPIRE trial.

Marie 8:50

Oh really.

Sharko 8:51

Yeah, so traditionally researchers, they focused on, you know, functional tests.

Marie 8:56

Yeah.

Sharko 8:56

Like walking speed or grip strength.

Marie 8:58

Right.

Sharko 8:58

But in this trial they've incorporated patient-reported outcomes.

Marie 9:02

That's great.

Sharko 9:03

Yeah, so they're capturing how patients are feeling.

Marie 9:05

Yeah.

Sharko 9:06

And functioning in their daily lives. Makes sense Because you know a slight improvement in walking speed might not mean much if a patient is still struggling with you know fatigue or pain Right. So capturing those subjective experiences provides a much richer and more meaningful picture.

Marie 9:25

Definitely.

Sharko 9:25

Of how a treatment is truly impacting someone's life.

Marie 9:29

Absolutely. It's a shift towards a more holistic and patient-centered approach to evaluating treatment success.

Sharko 9:36

I like that.

Marie 9:37

And it wouldn't have happened without the involvement of the CMT community.

Sharko 9:41

Exactly so, as we kind of look to the future, what does all this mean for CMT research as a whole?

Marie 9:49

That's a good question.

Sharko 9:50

You know, we've seen how quickly progress can happen with the right focus, with collaboration, with patient engagement.

Marie 9:57

Right.

Sharko 9:57

Is there a sense of optimism?

Marie 9:59

I think there is.

Sharko 10:00

That this momentum can be sustained.

Marie 10:02

I think there's definitely a renewed sense of hope within the CMT community. You know the success with CMTS sort. It's really shown that these challenges can be overcome and it sparked this wave of innovation and collaboration.

Sharko 10:16

Yeah.

Marie 10:16

So researchers, clinicians, patients, advocacy organizations they're all joining forces to really push the boundaries of what's possible.

Sharko 10:24

That's great yeah. Boundaries of what's possible? That's great yeah. And as we uncover more genetic causes of CMT, could we see a future where treatments are tailored to specific subtypes?

Marie 10:33

Potentially.

Sharko 10:34

Leading to more personalized and effective therapies.

Marie 10:36

That's the ultimate goal.

Sharko 10:37

Yeah Well, this has been an incredibly insightful conversation. It has we covered a lot of ground, from the science behind CMT sword to the impact this research is having on the community and beyond.

Marie 10:48

We have. It's been a fascinating exploration.

Sharko 10:50

It really has.

Marie 10:51

Of how scientific breakthroughs, patient empowerment and community collaboration can really come together to create hope for the future.

Sharko 10:58

Well, thank you so much for sharing your expertise with us today.

Marie 11:01

Oh, it's been my pleasure.

Sharko 11:02

Thank you for joining us on this deep dive.

Marie 11:05

Thanks for listening.

Sharko 11:06

Until next time, keep exploring, keep learning and never stop believing in the power of discovery.

Speaker 1 11:12

Thank you for listening to CMT Simplified. To learn more about HNF and 2025 Summit, visit hnf-cureorg. Join CMT families around the world, creating impact that matters.