Determinants of hepatic enzyme elevations following onasemnogene abeparvovec: Results from a unified immunomodulation protocol

Abstract

Introduction

Onasemnogene abeparvovec is an adeno-associated virus serotype 9 (AAV9) gene therapy for spinal muscular atrophy (SMA) that is frequently associated with immune-mediated hepatotoxicity. Previous studies have suggested that older age and higher body weight may increase the risk or severity of hepatic enzyme elevation; however, interpretation is limited by heterogeneous immunosuppression strategies across centers.

Method

We conducted a retrospective cohort study of children with SMA who received onasemnogene abeparvovec between 2020 and 2025 and were managed using a unified, protocol-driven immunomodulation strategy. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values (upper limit of normal [ULN] 35 U/L), as well as the timing of peak transaminase elevations, were analyzed in relation to age and weight at infusion.

Results

Among 152 children with adequate biochemical follow-up, hepatic enzyme elevation was common: 63.2% had peak ALT ≥2× ULN and 29.6% had peak ALT ≥5× ULN. Weight demonstrated a statistically significant but modest correlation with peak ALT magnitude (r = 0.184, p = 0.023), whereas age was not associated with transaminase severity. In contrast, age correlated with delayed timing of peak ALT (r = 0.229, p = 0.005) and AST (r = 0.283, p < 0.001). All hepatic enzyme abnormalities resolved under protocol-based immunomodulation, and no cases of hepatic failure or synthetic dysfunction occurred.

Conclusion

When managed with a structured, proactive immunomodulation protocol, hepatotoxicity following onasemnogene abeparvovec is predictable and manageable. Weight modestly influences ALT severity, while age primarily affects the timing rather than the magnitude of hepatic immune activation, supporting safe administration across a broad pediatric age and weight spectrum.

Keywords

onasemnogene abeparvovec spinal muscular atrophy hepatic enzyme elevation hepatotoxicity

Introduction

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of anterior horn cells in the spinal cord, leading to progressive muscle weakness, respiratory decline, loss of functional abilities and early mortality.¹ In most affected individuals, the disease results from biallelic deletions or pathogenic variants in the SMN1 gene, which produce a near-complete absence of survival motor neuron (SMN) protein. Phenotypic severity is strongly influenced by the copy number of the SMN2 gene, which generates limited full-length SMN protein through alternative splicing; patients with fewer SMN2 copies manifest earlier and more severe disease.² Before the availability of disease-modifying therapies, SMA type 1 was the leading genetic cause of infant death worldwide.³

Onasemnogene abeparvovec, an adeno-associated virus serotype 9 (AAV9)-mediated gene replacement therapy delivering a functional SMN1 transgene, has transformed outcomes across SMA phenotypes.⁴ Administered as a single intravenous infusion at a dose of 1.1×10¹⁴ viral genomes per kilogram, it enables sustained SMN protein production and substantially alters survival, motor development and respiratory trajectories compared with natural history.⁵ As experience expands globally, gene therapy is increasingly administered beyond infancy, including heavier children and those with more advanced disease phenotypes as well as in children with type 3 or 4 after the introduction of intrathecal gene therapy (onasemnogene abeparvovec-brve).⁶ This expanding treatment population has renewed attention to the hepatic safety profile of AAV9 gene therapy, which remains the most frequent treatment-related adverse event.⁷

Hepatotoxicity following onasemnogene abeparvovec is widely recognized and reflects the immune response directed against AAV9 capsid proteins and transduced hepatocytes. Early post-marketing reports describe hepatic enzyme elevation in a substantial proportion of recipients, with ALT and AST elevations typically emerging during the first 2–8 weeks after infusion and often coinciding with prednisolone taper.^8,9 Although fulminant hepatic failure is rare, the majority of children experience some degree of biochemical liver injury and hepatic enzyme elevation is observed in a substantial proportion of children. This therefore requires close monitoring and timely immunomodulation.

Several pathophysiological mechanisms have been proposed to explain AAV9-related hepatotoxicity. AAV9 exhibits natural tropism for hepatocytes.¹⁰ After systemic infusion, the capsid is internalized by hepatocytes and Kupffer cells, activating innate immune pathways including TLR9 and cGAS–STING, with downstream release of inflammatory cytokines such as IL-6, TNF-α and type-I interferons.¹¹ Subsequently, antigen presentation of capsid-derived peptides leads to capsid-specific CD8⁺ T-cell responses targeting transduced hepatocytes, resulting in hepatocellular injury. This biphasic immune process, with an early innate rise in liver enzymes, followed by a second flare triggered by adaptive immunity during corticosteroid taper has been well described and underpins modern immunosuppression strategies.¹² The second peak of transaminases, typically observed between weeks 4 and 8, is thought to reflect the transition to an adaptive, T-cell–mediated immune response. This phase may be relatively less responsive to corticosteroid monotherapy, and elevations are often observed during the period of corticosteroid taper, reflecting the temporal emergence of an adaptive immune process rather than a direct consequence of steroid withdrawal. Corticosteroids attenuate both innate and adaptive responses, whereas tacrolimus blocks IL-2 transcription and limits T-cell proliferation, offering targeted suppression during the adaptive phase.^13,14 Many real-world centers employ steroid escalation or additional immunosuppressants when transaminases rise significantly.

Historically, several studies have suggested that heavier or older children may be at higher risk of severe hepatotoxicity following AAV9 therapy, largely due to the weight-based dosing paradigm, whereby heavier recipients receive greater total vector loads. European and North American cohorts have reported associations between higher weight and elevated ALT/AST values, as well as prolonged steroid requirements.^15,16 The Phase 3b SMART study noted that infants older than 8 months often required longer or intensified corticosteroid courses.¹⁷ These findings have shaped the widespread assumption that hepatic enzyme elevation severity is intrinsically linked to weight or age. However, interpretation is complicated by substantial heterogeneity across centers, including differences in steroid dose adjustment, escalation thresholds, monitoring frequency, and the use of intravenous methylprednisolone or other immunosuppressants like rituximab or tacrolimus.^18,19 Most published cohorts also derive from genetically and ethnically homogenous populations and include primarily infants rather than older children. Furthermore, AST elevations are confounded by muscle breakdown in SMA, making ALT a more specific marker of hepatocellular injury.²⁰

Despite growing global experience, the predictive value of age and weight under uniform, proactive immune modulation remains unclear. Although tacrolimus is widely used in immune-mediated liver injury, few SMA cohorts have reported structured use of calcineurin inhibitors during AAV9-induced hepatic enzyme elevation.

Our center in Dubai functions as a major regional referral hub, treating children from more than seventeen countries across the Middle East, North Africa, Eastern Europe, Central Asia and South Asia.²¹ Importantly, our clinical practice implements a structured, tiered immune-modulation protocol combining baseline prednisolone prophylaxis with clearly defined escalation thresholds, early high-dose intravenous methylprednisolone for transaminase elevations ≥3× ULN, and tacrolimus for steroid-refractory cases. Steroid-refractory hepatic enzyme elevation was defined as failure of ALT and/or AST to show a downward trend on two consecutive weekly blood tests (approximately 14 days) following pulse intravenous methylprednisolone, with absolute enzyme levels remaining ≥4× ULN. In such cases, tacrolimus was introduced to provide calcineurin inhibitor–mediated T-cell suppression.

Our immunomodulatory approach was expert-based and evidence-informed, developed through multidisciplinary clinical experience with input from paediatric hepatology and guided by emerging literature on AAV-associated hepatotoxicity. However, this protocol was not derived from a formal Delphi process or prospective multicentre consensus. In addition, because this was a retrospective single-centre study without a comparator group treated strictly according to standard SmPC recommendations, our findings should not be interpreted as proof that this proactive regimen is superior to other approaches, nor as evidence that identical steroid escalation is required across all age groups. The optimal age- or weight-stratified immunosuppressive strategy, particularly in very young infants, remains uncertain and warrants prospective multicentre evaluation.

This framework offers the opportunity to examine hepatic outcomes in a uniquely diverse real-world population and to evaluate whether earlier assumptions about weight- or age-dependent risk persist under aggressive and consistent management.

The primary objective of this study was to describe the pattern, severity and timing of hepatic enzyme elevations following onasemnogene abeparvovec in this large multinational cohort. Secondary objectives were to evaluate whether weight or age predicted either the magnitude (peak ALT or AST) or the timing (week of peak) of hepatic enzyme elevation, and to assess how many children required escalation of immunosuppression or tacrolimus rescue. We hypothesized that under uniform proactive therapy, previously reported demographic risk factors might be attenuated, thereby challenging traditional assumptions about the determinants of AAV9 hepatotoxicity.

Methods

This retrospective observational cohort study included all children who received onasemnogene abeparvovec at a major regional gene therapy center in Dubai between November 2020 and November 2025. Ethical approval was obtained from the Local Ethics Committee (Ref: MRSH-EA-002). Written informed consent was obtained from parents or legal guardians for gene therapy administration. The requirement for additional informed consent for this retrospective analysis of de-identified clinical data was waived by the ethics committee.

Demographic variables collected included age at infusion (months), weight at infusion (kg), sex, and SMA type. All laboratory values were sourced from the institution’s central accredited laboratory.

Each child received a standard single-dose intravenous infusion of onasemnogene abeparvovec at 1.1×10¹⁴ viral genomes per kilogram. As per the standard guidelines, baseline prophylaxis with oral prednisolone 1 mg/kg/day commenced 24 hours before infusion and was continued for 30 days unless escalation criteria were triggered earlier. After this period if no escalation was needed, the dose was tapered while the patients were monitored with weekly liver function tests.¹⁹ The study site followed a unified immune-modulation protocol that was applied consistently across the entire cohort. Liver enzyme trends were interpreted relative to a fixed upper limit of normal (ULN) of 35 U/L for ALT and AST. The institutional immunomodulation protocol followed a tiered escalation strategy based on the magnitude and trajectory of transaminase elevation (Box 1).

Box 1. Tiered Immunomodulation Protocol for AAV9-related Hepatotoxicity

The following structured, proactive framework was utilized for all patients to manage hepatic immune responses following onasemnogene abeparvovec infusion:

• Tier 1 – Prophylaxis: Prednisolone 1 mg/kg/day initiated 24 hours before infusion and continued for 30 days.

• Tier 2 – Steroid Escalation: Prednisolone increased to 2 mg/kg/day if ALT or AST ≥2× ULN.

• Tier 3 – Steroid Intensification: If ALT or AST ≥3× ULN or continued to rise on follow-up testing despite Tier 2 escalation, intravenous methylprednisolone (30 mg/kg/day for three consecutive days) was administered, followed by oral prednisolone 2 mg/kg/day with a gradual taper.

• Tier 4 – Steroid-Refractory Rescue: Defined as failure of ALT and/or AST to show a downward trend on two consecutive weekly blood tests (i.e., over approximately 14 days) following completion of pulse intravenous methylprednisolone, with absolute enzyme levels remaining ≥4× ULN. In these cases, tacrolimus was introduced to provide calcineurin inhibitor–mediated T-cell suppression.

ULN = Upper Limit of Normal

For steroid-refractory cases, tacrolimus was used as a second-line immunomodulatory agent. Weight-based dosing was adjusted via therapeutic drug monitoring to achieve target trough levels between 5 and 7 ng/mL. Tacrolimus was discontinued once serum ALT and AST values had returned to the normal reference range, following clinical review and confirmation of biochemical stability.

Post-infusion monitoring included weekly ALT and AST for the first ten weeks, then biweekly depending on enzyme trajectory. Additional tests included complete blood count, coagulation profile (prothrombin time, international normalized ratio [INR], activated partial thromboplastin time [aPTT], and thrombin time), and troponin-I. Children requiring escalation were co-managed with pediatric hepatology, and liver ultrasound was performed when clinically indicated.

Peak ALT and peak AST values were extracted for each child, expressed in U/L and as multiples of ULN. The week in which the peak occurred was determined from serial laboratory records. Outcomes of interest included peak severity, week of peak, and immunomodulation requirements. Descriptive statistics (mean ± standard deviation, median with interquartile range, and percentages) were used as appropriate. Pearson correlation coefficients were used to quantify associations between age, weight, and hepatic outcomes. To account for potential confounding between demographic variables, multivariable linear regression analyses were also performed including age and weight as predictors of peak transaminase magnitude and timing. Statistical significance was set at p < 0.05. Analyses were performed using SPSS version 28. Because peak ALT values demonstrated a right-skewed distribution, sensitivity analyses using log-transformed ALT values were conducted, which did not materially change the results.

Results

A total of 159 children were infused between November 2020 and November 2025. Of these, 7 children lacked the minimum required biochemical monitoring (at least five weeks of AST/ALT data including baseline), resulting in a final analytic cohort of 152 (Figure 1).

Figure 1.

Patient Disposition and Cohort Characteristics

All patients included in the cohort were clinically symptomatic for spinal muscular atrophy, although symptom severity varied across individuals. Among the 152 treated patients, 52 (34.2%) required invasive ventilation via tracheostomy, while 21 (13.8%) were receiving non-invasive ventilatory support (BiPAP). Most patients in our cohort had previously received nusinersen prior to gene therapy. Although prior reports have suggested a potential association between nusinersen exposure and transaminase elevations following onasemnogene abeparvovec,²² this relationship was not specifically evaluated in the present study.

The median weight was 10 kg (IQR 8–12 kg; range 5–20 kg). SMA type distribution was dominated by SMA type 1 (n=116, 76%), followed by type 2 (n=34, 23%) and type 3 (n=2, 1%). Sex distribution was 82 males (54%) and 70 females (46%) (Table 1). Baseline ALT and AST values were normal in all children, and none exhibited preexisting hepatic impairment.

Table 1.

Patient demographics.

Characteristic	Value
Age at Infusion (Months)
Mean +/- SD	29.9+/-18.2
Median (IQR)	24.0 (16.0–39.0)
Range	4.0–89.0
Weight at Infusion (kg)
Mean +/- SD	10.1 +/- 3.1
Median (IQR)	10.0 (8.0–12.0)
Range	5.0–20.0
Sex Ratio (Male: Female)	54%: 46% (n=82 Male, n=70 Female)
SMA Clinical Type
Type 1	76% (n=116)
Type 2/3	24% (n=36)

Hepatic enzyme elevation was common. The distribution of peak transaminase elevations is summarized in Table 2. Most patients experienced mild-to-moderate enzyme elevations, with 70.4% of ALT values and 71.1% of AST values remaining below 5× ULN. Severe elevations (>20× ULN) were uncommon, occurring in 5.9% of patients for ALT and 3.3% for AST. The median peak ALT was 2.87 × ULN (IQR 1.4–6.0), and the median peak AST was 3.37 × ULN (IQR 2.4–5.83). ALT and AST were strongly correlated (r=0.92, p < 0.001), reflecting their parallel rise during immune-mediated hepatic injury despite AST’s lower hepatic specificity.

Table 2.

Distribution of peak transaminase elevation following onasemnogene abeparvovec.

Peak transaminase elevation (× ULN^†)	ALT n (%)	AST n (%)
<2× ULN	56 (36.8%)	19 (12.5%)
≥2– <5× ULN	51 (33.6%)	89 (58.6%)
≥5– <10× ULN	23 (15.1%)	23 (15.1%)
≥10– <20× ULN	13 (8.6%)	16 (10.5%)
≥20× ULN	9 (5.9%)	5 (3.3%)

†ULN = upper limit of normal (35 U/L).

Most children exhibited an early rise in ALT and AST within the first three weeks, consistent with innate immune activation. A second rise occurred during weeks 4–6 in many children, coinciding with corticosteroid taper and reflecting adaptive T-cell–mediated hepatocyte injury (Figure 2). The median week of peak AST was week 3 (IQR 1–5), and the median week of peak ALT was week 4 (IQR 1–6). Over 93% of all peaks occurred within eight weeks of infusion. In the overall cohort, the mean time for serum ALT and AST levels to return to the normal reference range was approximately eight weeks after onasemnogene abeparvovec administration. The early predominance of AST over ALT observed in the first weeks following infusion may partly reflect extra-hepatic sources of AST, including erythrocytes or skeletal muscle, in addition to hepatic injury. Complement activation markers were not routinely measured in this cohort, and no consistent association between elevated AST:ALT ratios and thrombocytopenia was observed.

Figure 2.

Weekly ALT and AST kinetics following onasemnogene abeparvovec.

The timing of peak transaminase elevations showed considerable variability. A subset of patients experienced delayed peaks beyond the typical early post-infusion period. This delay demonstrated a significant positive association with age at infusion. Age showed a weak but statistically significant correlation with the week of peak ALT (r = 0.211, p = 0.009) and week of peak AST (r = 0.242, p = 0.003), and this relationship remained significant in multivariable regression analysis. These relationships are illustrated in Figure 3, which demonstrates the progressive delay in peak transaminase elevation with increasing age at infusion.

Figure 3.

Relationship between age at infusion and timing of peak transaminase elevations.

Age was not significantly associated with transaminase severity (Supplementary Figure S1). There was no significant correlation between age and peak ALT (r = 0.120, p = 0.141) or peak AST (r = 0.008, p = 0.919). Although some younger patients demonstrated very high peak transaminase values (>20× ULN), regression analysis showed no significant association between age and peak transaminase magnitude. These observations likely reflect individual variability within the cohort rather than an age-dependent effect. In contrast, body weight demonstrated a modest association with ALT severity. This association is illustrated in Figure 4. Visual subgroup comparisons may therefore appear inconsistent due to sample distribution and variability within smaller weight categories. Weight was not significantly associated with peak AST (r = 0.089, p = 0.273) (Supplementary Figure S2; Table 3).

Figure 4.

Relationship between weight at infusion and peak ALT elevation.

Table 3.

Correlation with peak transaminase magnitude.

Predictor	Outcome	Pearson r	P-value
Weight (kg)	Peak ALT (× ULN^†)	0.184	0.023^*
Age (months)	Peak ALT (× ULN)	0.120	0.141
Age (months)	Peak AST (× ULN)	0.008	0.919
Weight (kg)	Peak AST (× ULN)	0.089	0.273

†ULN = upper limit of normal (35 U/L).

*p < 0.05 considered statistically significant.

To account for potential confounding between age and weight, multivariable linear regression analyses were performed. Age remained independently associated with the timing of peak ALT elevation (β = 0.076, p = 0.012) while adjusting for weight. Weight showed a modest association with peak ALT magnitude (β = 0.51), although this did not reach statistical significance after adjustment (p = 0.083). Sensitivity analyses using log-transformed ALT values yielded similar results.

Immunomodulation requirements were substantial but effective. Prednisolone escalation was required in 42% of children, intravenous methylprednisolone in 11%, and tacrolimus in 7% of the cohort. All children achieved full normalization of transaminases, and no episodes of hepatic failure, clinical hepatitis, synthetic dysfunction, coagulopathy or hyperbilirubinemia occurred.

Discussion

This large multinational real-world cohort provides important evidence regarding the determinants, kinetics and clinical implications of hepatotoxicity after onasemnogene abeparvovec. Our findings suggest that age influences the timing of peak transaminase elevation, whereas weight shows only a modest association with transaminase severity. However, the effect size is small, suggesting the risk is manageable. The findings challenge several long-standing assumptions, clarify the relative contributions of demographic factors, and highlight the central role of structured immune modulation in ensuring hepatic safety across a broad age and weight spectrum.

Hepatic enzyme elevation was extremely common, affecting most children, consistent with prior data and reflecting the expected biphasic immune response to AAV9 capsid. However, despite the high biochemical incidence, all hepatotoxicity resolved fully under structured immune modulation, and no clinically significant liver injury occurred. This demonstrates that even substantial ALT elevations can be safely managed with proactive escalation and that severe outcomes can be fully prevented.

The relationship between weight and severity of hepatic enzyme elevation was modest. In our cohort, weight at infusion showed a small correlation with peak ALT magnitude and no significant association with peak AST. These findings are consistent with the theoretical expectation that heavier children may receive a larger total viral load, which could contribute to hepatocellular injury. However, the magnitude of this effect in our study was considerably lower than that reported in several landmark North American and European cohorts. One possible explanation may relate to differences in immunosuppression management. In previous studies, heterogeneous or reactive steroid protocols may have allowed immune-mediated inflammation to progress unchecked, thereby magnifying the impact of viral load.^23–25 In contrast, our proactive escalation strategy may attenuate this gradient, although this hypothesis would require confirmation in comparative studies.

Our findings suggest that age influences the timing of peak transaminase elevation, whereas weight shows only a modest association with transaminase severity. Older children experienced significantly later peaks in ALT and AST, supporting the concept that age influences the kinetics of immune activation rather than its magnitude. Older recipients may mount slower adaptive responses due to immunological maturation, differences in hepatic antigen presentation or altered steroid pharmacodynamics.^26–28 This has key implications for monitoring- older children require longer post-infusion surveillance, particularly during steroid taper, even if initial enzyme values are stable.

Population-based observational data from the DA-CH region (Germany, Austria, and Switzerland) have similarly reported that the risk of liver enzyme elevation increases with age and weight at infusion, particularly in children treated after two years of age.²⁹ Our findings are broadly consistent with these observations, although in our cohort age appeared to influence the timing of peak enzyme elevation more strongly than its magnitude.

The SMART study, which specifically evaluated heavier children (up to 21 kg), confirmed that onasemnogene abeparvovec can be administered safely to this demographic, but noted that hepatic enzyme elevation remained the most common treatment-emergent adverse event.¹⁷ Our findings support the growing evidence that heavier children can be treated safely when structured immunomodulation protocols are used. However, while the SMART study observed that heavier cohorts often required intensified or modified corticosteroid management, our cohort utilized a structured “rescue” framework featuring tacrolimus in 7% of cases to achieve full biochemical resolution. Our results are also consistent with the RESTORE registry,³⁰ which recently reported a hepatotoxicity prevalence of approximately 29.3%. Although hepatic enzyme elevation was more frequent in our cohort (63.2% ≥2× ULN) the universal reversibility and lack of synthetic dysfunction or hepatic failure in our 152 patients underscore the safety of gene therapy when paired with a proactive, tiered immunomodulation strategy.

The structured immunomodulation protocol was critical to these favorable outcomes. Early prednisolone escalation controls innate cytokine-mediated injury, intravenous methylprednisolone arrests rising enzymes during the transition to the adaptive phase, and tacrolimus provides calcineurin inhibitor–mediated T-cell suppression when steroids alone are insufficient. The low threshold for escalation and consistent application across all children ensured timely suppression of hepatic inflammation, preventing progression to clinically significant liver injury.

These observations position hepatotoxicity as a predictable and manageable phenomenon when robust protocols are used. The study supports the harmonization of immune-modulation strategies across international gene therapy centers and highlights the need for age-specific monitoring schedules. Additionally, the unique multinational composition of this cohort demonstrates that findings are applicable across diverse ethnic, geographic and genetic backgrounds, strengthening their relevance to global practice. As many families travel internationally for accessing gene therapy,^21,31 structured protocols ensure safety across diverse populations. Our findings support establishing international consensus protocols, including clear thresholds for steroid doubling, criteria for escalation therapies such as intravenous methylprednisolone and tacrolimus, as well as standardized laboratory monitoring schedules.

Strengths of this study include its large sample size, uniform immune-modulation protocol, and multinational cohort that enhances global generalizability. Limitations include the retrospective design, lack of immunophenotyping or cytokine profiling, and absence of a comparator cohort not using aggressive immunomodulation. Because our study lacks a comparator cohort treated under alternative protocols, this observation should be interpreted cautiously and cannot establish a causal relationship. It is plausible that more proactive escalation strategies may attenuate the influence of viral load on hepatotoxicity, but this hypothesis requires confirmation in prospective comparative studies.

Tacrolimus trough levels were not uniformly available for all patients. Nonetheless, the large sample size, consistent protocol and detailed enzyme kinetics provide substantial insight into AAV9 hepatotoxicity and its determinants.

Conclusion

In this large multinational cohort, hepatic enzyme elevation was common but universally reversible under a structured, proactive immune-modulation protocol incorporating steroid escalation and tacrolimus rescue. Weight showed only a modest association with ALT severity, whereas age predicted the timing, but not the magnitude, of hepatic immune activation. These findings challenge previously proposed assumptions regarding weight-related risk and emphasize the importance of protocol-driven immunosuppression in mitigating hepatotoxicity following onasemnogene abeparvovec. When managed with consistent early intervention, onasemnogene abeparvovec can be safely administered across a broad pediatric age and weight spectrum.

Supplemental material

Supplemental material - Determinants of hepatic enzyme elevations following onasemnogene abeparvovec: Results from a unified immunomodulation protocol

Supplemental material for Determinants of hepatic enzyme elevations following onasemnogene abeparvovec: Results from a unified immunomodulation protocol by Vivek Mundada, Syon Parashar, Anil Dhawan in Journal of Neuromuscular Diseases

Supplemental material

Supplemental material - Determinants of hepatic enzyme elevations following onasemnogene abeparvovec: Results from a unified immunomodulation protocol

Footnotes

Acknowledgements

The authors would like to express their gratitude to Dr. Shaista Amin (Consultant Paediatric Gastroenterologist, American Hospital Dubai) for her clinical support. We also extend our sincere thanks to the children and their parents for their participation and contribution to this study.

ORCID iDs

Vivek Mundada

Anil Dhawan

Ethical considerations

Ethical approval was obtained from the Medcare Hospital, Dubai Ethics Committee (Ref: MRSH-EA-002).

Consent to participate

Written informed consent was obtained from parents or legal guardians for clinical gene therapy administration. The requirement for additional informed consent for this retrospective analysis of de-identified data was waived by the ethics committee.

Author contributions

VM (Vivek Mundada): Conceptualization; Methodology; Investigation (Clinical oversight of the 152-patient cohort); Project administration; Supervision; Writing – original draft; Writing – review & editing.

SP (Syon Parashar): Formal analysis; Data curation; Software; Validation (statistical verification of reported correlation and regression analyses); Writing – review & editing.

AD (Anil Dhawan): Methodology; Clinical protocol development (immunomodulation strategy); Supervision; Writing – review & editing.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The datasets generated and analyzed during the current study are not publicly available due to ethical restrictions related to participant confidentiality but are available from the corresponding author on reasonable request.*

Supplemental material

Supplemental material for this article is available online.

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