NSAA Alone Is Not Enough: Why Creatine Kinase (CK), AST, ALT, and Dystrophin Levels Should Be Disclosed

So why do many DMD clinical trials avoid clearly reporting these key biomarkers? This article examines why CK, AST, ALT, and dystrophin data matter—and why families pursuing treatment options should demand full transparency.

Duchenne muscular dystrophy (DMD) is one of the most devastating genetic neuromuscular disorders, characterized by progressive muscle degeneration caused by mutations in the dystrophin gene. Over the last decade, the therapeutic landscape has evolved rapidly with the development of gene therapies and exon-skipping drugs intended to restore or partially replace dystrophin expression. These therapies are often evaluated through clinical trials that report functional outcomes such as the North Star Ambulatory Assessment (NSAA).

While NSAA provides an important functional measurement of motor ability in ambulatory boys with Duchenne, relying on this metric alone can be misleading. Clinical improvements—or the lack thereof—may be influenced by growth, steroid treatment, or natural variability in disease progression. Biomarkers in Duchenne muscular dystrophy such as creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and dystrophin protein levels provide essential biochemical evidence of disease activity and therapeutic effect. Read More: What is Creatine Kinase (CK)?

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Despite their importance, many clinical trials and corporate press releases report only limited biomarker data, often emphasizing functional outcomes while omitting detailed biochemical measurements. This lack of transparency raises significant concerns for clinicians, researchers, regulators, and the Duchenne community.

Biomarkers in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy results from mutations in the dystrophin gene, leading to the absence or severe deficiency of dystrophin protein in muscle fibers. Without dystrophin, muscle cells are highly susceptible to damage during contraction, resulting in repeated cycles of degeneration and regeneration. Read More: What is dystrophin gene?

Biomarkers are essential for understanding disease activity and treatment effects in DMD.

Key biomarkers include:

Creatine Kinase (CK)
CK is a muscle enzyme released into the bloodstream when muscle cells are damaged. Elevated CK levels are one of the earliest biochemical indicators of DMD and reflect ongoing muscle injury. ¹

AST and ALT
Although commonly used as liver enzymes, AST and ALT are also elevated in Duchenne due to muscle breakdown. Changes in these enzymes may reflect muscle protection or treatment effects.

Dystrophin Expression
The ultimate therapeutic goal of most modern Duchenne therapies is restoring dystrophin expression. Measuring dystrophin levels in muscle biopsies provides direct evidence of whether a therapy is working at the molecular level. (Springer)

Together, these biomarkers provide biochemical confirmation of whether therapies are altering disease biology.

The Dominance of Functional Measures in Duchenne Trials

Many modern Duchenne trials emphasize functional endpoints such as:

• North Star Ambulatory Assessment (NSAA)
• Six-minute walk test (6MWT)
• Time to stand or climb stairs
• Timed motor function tests

These measures are important because they directly reflect patients’ physical abilities. However, they are also influenced by factors unrelated to the therapy itself.

For example:

• Young children may show temporary improvements due to normal development.
• High-dose corticosteroids can improve strength and function.
• Short-term functional improvements may not reflect long-term disease modification.

Researchers have repeatedly noted that improvements in NSAA scores during early-phase trials must be interpreted cautiously because untreated young patients may also show temporary functional gains due to natural growth.

This is why biomarkers in Duchenne muscular dystrophy are essential complementary evidence.

Gene Therapy and Exon-Skipping Treatments: A New Era

Recent years have seen an explosion in therapeutic development for Duchenne muscular dystrophy.

These include:

• AAV-based micro-dystrophin gene therapies
• Antisense exon-skipping therapies
• Gene editing approaches

Exon-skipping therapies work by modifying the dystrophin transcript to produce a shorter but partially functional protein. These therapies typically target specific mutations and may benefit only a subset of patients. Learn More: What is Exon Skipping?

Single-dose AAV-based microdystrophin gene therapies are designed to deliver a functional version of the dystrophin gene to patients’ muscles in a single treatment. While early trial results often highlight improvements in functional measures like the North Star Ambulatory Assessment (NSAA), these tests alone cannot confirm whether the therapy is truly protecting muscle tissue or restoring dystrophin at a molecular level.

Detailed reporting of biomarkers in Duchenne muscular dystrophy—such as creatine kinase (CK), AST, ALT, and dystrophin levels—is crucial because these biomarkers provide direct biochemical evidence of muscle health, ongoing degeneration, and therapeutic impact. CK levels indicate the degree of muscle damage, AST and ALT provide insight into muscle and liver enzyme activity, and dystrophin measurements demonstrate whether the therapy achieves its primary molecular target.

For families considering participation in clinical trials or evaluating access to newly approved therapies, transparent biomarker data can significantly influence their decision-making. Understanding how a therapy affects CK, AST, ALT, and dystrophin helps families weigh the potential benefits against the risks, such as immune responses or liver toxicity, that may arise from viral vector delivery.

Without access to detailed biomarker information, families must rely solely on functional scores or company press releases, which may not fully reflect treatment efficacy. Transparent reporting empowers families to make informed choices, advocate for necessary monitoring, and engage meaningfully with clinicians about the expected outcomes and long-term effects of single-dose AAV-based gene therapies.

The Problem: Limited Reporting of Duchenne Biomarkers Data

One of the most concerning issues in the Duchenne clinical research landscape is the selective reporting of results.

Many trial updates focus primarily on:

• NSAA improvements
• timed functional tests
• safety data

Yet they often provide minimal or incomplete biomarker data.

For example, company announcements may highlight functional improvements but omit:

• longitudinal CK measurements
• detailed AST/ALT trends
• individual dystrophin expression levels
• patient-level biomarker variability.

This selective reporting creates several problems.

1. Lack of Mechanistic Evidence

Without biomarkers in Duchenne muscular dystrophy data, it becomes difficult to determine whether a therapy is actually modifying the underlying disease process.

For example, if NSAA scores improve but CK levels remain unchanged, the functional improvement could be due to other factors such as steroid use or placebo effects.

2. Difficulty Comparing Therapies

The Duchenne therapeutic landscape now includes multiple gene therapies and exon-skipping drugs.

Without standardized biomarker reporting, comparing treatments becomes nearly impossible.

3. Reduced Scientific Transparency

Clinical trials should provide enough data for independent researchers to evaluate results. When biomarker information is missing or incomplete, it limits scientific scrutiny.

Duchenne Biomarkers Provide Early Signals of Efficacy

Biomarkers in Duchenne muscular dystrophy often provide the earliest signals that a therapy is working.

For example, reductions in CK levels can indicate reduced muscle damage following treatment. In one study of gene therapy recipients, CK levels decreased by approximately 44% shortly after treatment before stabilizing.

Such changes may occur months or even years before measurable improvements in motor function.

This is especially important in Duchenne because:

• functional decline occurs slowly
• trials may last only 12–24 months
• patient numbers are small.

Therefore, biomarkers provide critical evidence of biological activity.

Monitoring Safety: AST and ALT

Another major reason to report biomarkers is safety monitoring.

Gene therapies for Duchenne typically use adeno-associated virus (AAV) vectors. While these vectors are generally safe, they can cause immune reactions or liver toxicity.

AST and ALT levels are therefore closely monitored after gene therapy infusion.

A recent case report described delayed liver injury following AAV-based gene therapy, where ALT and AST levels increased dramatically before returning to baseline after treatment with immunosuppressive therapy.

Researchers also suggested that the ALT/CK ratio may serve as an early biomarker for detecting liver injury in Duchenne patients receiving gene therapy.

Without public reporting of these biomarkers, clinicians cannot fully evaluate the safety profile of these treatments.

Dystrophin: The Most Important Biomarker

Ultimately, the goal of many Duchenne therapies is restoring dystrophin.

Therefore, dystrophin levels should be one of the most important endpoints in clinical trials.

These measurements are typically obtained from muscle biopsies using:

• Western blot
• immunofluorescence
• mass spectrometry.

Yet dystrophin data are often presented in ways that make comparisons difficult.

For example:

• Percentage of dystrophin-positive fibers
• Dystrophin intensity relative to normal muscle
• Western blot percentages

Different trials may report dystrophin expression using different methods or normalization techniques.

This lack of standardization further complicates interpretation.

When Functional Outcomes and Biomarkers Do Not Align

In some trials, functional outcomes and biomarker data tell different stories.

For example:

• A therapy may show increased dystrophin expression but limited functional improvement.
• Functional improvements may occur without clear biomarker changes.

These discrepancies highlight why both types of data must be reported together.

A therapy that increases dystrophin expression but does not yet show functional benefits could still be disease-modifying. At this point, the biomarker that should be focused on is the creatine kinase (CK) level. Elevated creatine kinase (CK) levels indicate ongoing muscle damage.

Conversely, a therapy that improves functional scores without biochemical changes may be producing short-term symptomatic effects rather than altering disease progression.

The Role of Regulatory Agencies

Regulators such as the U.S. Food and Drug Administration or European Medicines Agency have increasingly relied on surrogate biomarkers when evaluating Duchenne therapies. Why Elevidys Was Not Approved by the European Medicines Agency (EMA)?

However, the approval of certain treatments has also been controversial. Learn More: Why Does the FDA Approve DMD Therapies That Fail in Clinical Trials?

Some experts have questioned whether clinical trial data provide sufficient evidence of long-term benefit, especially when primary endpoints such as NSAA were not met in certain studies.

This debate highlights the importance of transparent biomarker reporting.

The Patient Perspective

For families affected by Duchenne muscular dystrophy, clinical trial announcements often generate enormous hope.

However, incomplete data can create confusion.

Patients deserve to know:

• whether treatments reduce muscle damage
• whether dystrophin production increases
• whether biomarkers improve.

Transparent reporting helps patients make informed decisions about participating in clinical trials or receiving newly approved therapies.

The Need for Standardized Biomarker Reporting

The Duchenne research community should consider adopting standardized guidelines for biomarker reporting in clinical trials.

These could include:

Mandatory reporting of:

• Creatine Kinase (CK) levels
• AST and ALT trends
• Dystrophin expression levels
• Individual patient variability

Standardized measurement methods

Consistent laboratory methods would make comparisons across trials easier.

Long-term biomarker tracking

Because Duchenne progresses slowly, long-term biomarker monitoring is essential.

Toward Greater Transparency in Duchenne Research

The rapid pace of innovation in Duchenne therapy is encouraging.

However, transparency must keep pace with innovation.

Clinical trials should prioritize full reporting of:

• biochemical biomarkers
• molecular endpoints
• functional outcomes.

Only by combining these datasets can the Duchenne community truly evaluate the effectiveness of emerging therapies.

Frequently Asked Questions (FAQ) About Duchenne Clinical Trials and Biomarkers

Final Thoughts

Duchenne muscular dystrophy remains a devastating disease, but new gene therapies and exon-skipping treatments offer hope.

Yet hope must be accompanied by scientific rigor and transparency.

Functional measures like NSAA are important, but they cannot stand alone as evidence of therapeutic success.

Biomarkers in Duchenne muscular dystrophy such as Creatine Kinase (CK), AST, ALT, and dystrophin levels provide crucial insight into whether therapies are truly altering the disease process.

To ensure that patients, clinicians, and researchers can accurately assess these treatments, clinical trials must commit to comprehensive biomarker reporting.

Without this transparency, the Duchenne community risks making decisions based on incomplete evidence.

Follow This Page >>> All Clinical Trials for Duchenne

Sources and Academic References

1. Biomarkers in Duchenne Muscular Dystrophy: Current Status and Future Directions ↩︎
2. Development and Validation of a Western Blot Method to Quantify Mini-Dystrophin in Human Skeletal Muscle Biopsies ↩︎

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