Duchenne muscular dystrophy (DMD) has long been understood as a disease driven by the absence of dystrophin, a protein essential for maintaining muscle integrity. Most therapeutic efforts have focused on restoring dystrophin through gene therapy, exon-skipping, or other genetic approaches. However, emerging research suggests that dystrophin’s role extends beyond structural support — it also plays a critical part in regulating muscle regeneration. This discovery has opened the door to an entirely new therapeutic strategy.

Drug Discovery News spoke with Frank Gleeson, the co-founder, CEO, and Board Director of Satellos, to discuss the science behind his Company’s novel, dystrophin-independent approach, its potential impact on people living with DMD, and what it could mean for the future of muscle-related conditions.

What inspired Satellos to take a dystrophin-independent approach to treating DMD?

Our approach stems from pioneering research by Satellos co-founder Michael Rudnicki. His discovery revealed that aside from playing a role in maintaining muscle cell integrity, dystrophin also functions as a signaling molecule that triggers muscle stem cells to undergo asymmetric cell division. This process is essential for muscle regeneration and repair, as each asymmetric cell division generates both a new stem cell and a muscle progenitor cell. Without the dystrophin signal, insufficient asymmetric divisions occur, leading to a shortage of progenitor cells and progressive, debilitating muscle loss. These findings redefined DMD as a disease of failed muscle regeneration, guiding our focus toward restoring the body’s capacity to create new muscle and improved function through innate regeneration.

Could you explain the biological approach you’ve identified and how it differs from the mechanisms targeted by dystrophin-focused therapies?

Instead of attempting to genetically restore dystrophin, which does not restore regeneration, we sought a method to restore asymmetric cell divisions to promote muscle regeneration. This led to the development of SAT-3247, a first-in-class small molecule drug that inhibits adaptor-associated protein kinase 1. By blocking this protein, we restore the signal that cells need to undergo asymmetric divisions and progenitor muscle cell production.

Satellos has demonstrated this can be effective both in vitro and in animal models. Our approach is a fundamental departure from existing therapies, which aim to compensate for dystrophin loss through genetic interventions like exon-skipping or gene therapy. These approaches do not replace the missing signal needed to make new muscle cells, whereas our approach leverages the body’s natural regenerative mechanisms, completely independent of dystrophin.

What challenges did you face in developing treatments that aim to restore muscle function without dystrophin, and how were they overcome?

One of the biggest hurdles was challenging the long-held belief that dystrophin is essential for muscle to be functional. Our team revisited clinical observations, including cases of DMD patients who retained mobility despite completely lacking dystrophin. These insights led us to explore dystrophin’s role as a signal transduction molecule guiding asymmetric stem cell division.

By rigorously validating our hypothesis through preclinical studies and extensive biological research, we demonstrated that correcting the defective process of asymmetric division in muscle stem cells can restore functional muscle regeneration and effectively compensate for the absence of dystrophin. Overcoming skepticism required meticulous scientific inquiry and evidence-based validation in animal models and, at times, a thick skin.

Your first treatment is now in clinical trials. What key outcomes are you aiming to demonstrate at this stage?

In September 2024, we launched a Phase 1 randomized, placebo-controlled study to assess the safety and pharmacokinetics of SAT-3247. In this first stage, which is now completed, we treated 72 healthy volunteers across multiple single and ascending dose (SAD/MAD) cohorts and one cross-over food effect cohort. In the second stage, which is underway now, we plan to treat up to 10 adult DMD patients to evaluate SAT-3247’s safety and PK profiles in patients. These studies may also help identify pharmacodynamic markers.

How might this approach change the standard of care for DMD if proven effective?

In Phase 1 development to date, SAT-3247 has shown a very favorable safety profile. As an orally available small molecule drug, it has the potential to provide flexibility and tolerability unmatched by current treatments. Since it targets regeneration rather than dystrophin restoration, it may be used as either a primary or adjunctive therapy — potentially benefiting a broader population of DMD patients, regardless of treatment history. Additionally, by enhancing muscle repair rather than merely slowing disease progression, our treatment may lead to earlier and more noticeable clinical benefits.

Are there specific patient populations within the DMD community who may benefit most from your therapy?

Because our therapy focuses on muscle regeneration rather than mutation-specific correction, it has the potential to benefit all DMD patients, regardless of their genetic profile. Moreover, our preclinical studies suggest that SAT-3247’s regenerative capabilities may provide earlier improvements in muscle function compared to existing treatments. Future clinical trials will help determine if these animal studies translate to human patients and which patient subgroups experience the most significant benefits.

Given that DMD patients can create muscle as they grow despite lacking dystrophin, how does your research reshape our understanding of muscle regeneration?

Our findings reinforce the idea that muscle regeneration in DMD is impaired due to deficient progenitor cell production rather than structural weakness. This explains why some DMD patients, known as “escapers,” retain mobility despite lacking dystrophin — suggesting an alternative regenerative mechanism is at play. By restoring this function, we aim to improve muscle repair even in dystrophin-null patients.

Could the approach you’ve identified have applications beyond DMD, perhaps in other muscular or degenerative diseases?

Yes, we believe our approach could be applied to other muscle-related disorders. Our preclinical studies suggest that SAT-3247 is effective in models of facioscapulohumeral muscular dystrophy (FSHD), another condition characterized by impaired muscle regeneration. Additionally, our research indicates potential applications in muscle injuries, sports medicine and even cancer-related muscle wasting. By targeting how muscle stem cells divide to create new muscle, our therapy could address a wide range of conditions involving muscle degeneration and repair deficits.

What role do partnerships — whether with patient advocacy groups, academic researchers, or other biotech companies — play in advancing Satellos’ mission?

Partnerships are crucial for our success. We collaborate with patient advocacy groups to gain insights into patient needs, navigate regulatory challenges and foster community support. Very early on at Satellos, we received encouragement and financial support from Parent Project Muscular Dystrophy (PPMD) and benefited greatly from their guidance. Rudnicki’s deep ties within the research community provide access to cutting-edge science that informs our drug discovery efforts. Additionally, strategic partnerships down the road with biopharmaceutical companies can accelerate development and maximize patient impact, ensuring our therapy reaches those who need it most.

What’s your long-term vision for Satellos in transforming the treatment landscape for DMD and other muscle-related conditions?

While Duchenne remains our primary focus, we envision our approach as a platform technology with broad potential. We are actively exploring applications in other muscular dystrophies, injury recovery and conditions like cancer-related muscle wasting. Our goal is to establish a new paradigm in muscle repair — one that enhances stem cell function to restore and maintain muscle integrity across a variety of diseases and conditions.

How do you address concerns or skepticism from the medical community about shifting away from dystrophin-focused therapies?

Rather than abandoning dystrophin-focused therapies, we see our approach as expanding treatment options for DMD patients. Given the heterogeneity of the disease, no single therapy will be suitable for all patients. Our goal is to provide an alternative that complements existing treatments, ensuring a greater number of patients receive effective care.

What steps are you taking to ensure equitable access to these potentially groundbreaking treatments once they are approved?

One of the key advantages of SAT-3247 is its nature as a small molecule drug, making it easier to manufacture and distribute compared to gene therapies. Additionally, because our approach is not mutation-specific, it has the potential to be offered to all DMD patients, simplifying accessibility. We are committed to working with regulatory bodies and healthcare providers to ensure broad and equitable access once our therapy reaches the market.