Background: Spinal muscular atrophy (SMA) is a rare neuromuscular disease and the most common genetic cause of infant death. Although pharmacological treatment improves survival rates and functional capacity, physiotherapy remains a key component of care. A newly developed innovative equine-assisted physiotherapy method based on neuroproprioceptive “facilitation and inhibition” principles (NEUROEQUIP-SMA) is hypothesized to improve the quality and extent of motor development in children with SMA. Objective: The aim of this study is to assess the efficacy of NEUROEQUIP-SMA compared with standard individual outpatient physiotherapy based on the same neuroproprioceptive “facilitation and inhibition” principles (SMA-SOC-N) and to evaluate its effects on functional outcomes and quality of life (QoL). In addition, the response of molecular biomarkers to treatment will be assessed. Methods: In this crossover randomized controlled trial, 20 children with SMA types I-III, aged 2‐9 years, will participate in two 6-day therapy programs (A and B) of equal duration (50 min per day) and separated by a 10-week washout period. Each child will be randomly assigned to receive the therapies in either the AB or BA sequence. Therapy A consists of a newly developed NEUROEQUIP-SMA (15 min twice daily), whereas therapy B involves SMA-SOC-N (30 min once daily). Both programs include therapeutic horse grooming (20 min a day). The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) was selected as the primary outcome measure. Secondary outcomes included motor coordination assessed through 3D motion analysis, muscle fatigue, spirometry, and standardized clinical tests and rating scales, as well as monitoring of psychomotor development (via home-video analysis) and QoL (via questionnaires). Molecular biomarkers will be analyzed from blood samples. The immediate effect of the intervention will be evaluated for most outcomes, while psychomotor development and QoL will be monitored 28 days after therapy as longer-term outcomes. Treatment effect sizes will be reported alongside P values to illustrate the magnitude of changes in the outcomes. The study was approved by the Ethics Committee of the Third Faculty of Medicine, Charles University, under the number UK3LF/658559/12025. Results: The study is designed for 20 participants. Data collection will begin in February 2026 and will be completed in May 2026. Data analyses are planned for autumn 2026, and study results are expected to be available in 2027. A paired t test comparing the primary outcome (CHOP INTEND) between treatments NEUROEQUIP-SMA and SMA-SOC-N in 20 children will have 80% power to detect moderate-to-large effect size (Cohen d =0.66) at a 5% significance level. Conclusions: This trial will be the first study to evaluate the effects of NEUROEQUIP-SMA in children with SMA. If preliminary findings confirm a benefit, this physiotherapy approach may represent a promising adjunct to care for the generation of children undergoing gene therapy.

BACKGROUND Spinal muscular atrophy (SMA) is a rare neuromuscular disease and the most common genetic cause of infant death. Although pharmacological treatment improves survival rates and functional capacity, physiotherapy remains a key component of care. A newly developed innovative equine-assisted physiotherapy method based on neuro-proprioceptive “facilitation and inhibition” principles (NEUROEQUIP-SMA), could potentially improve the quality and extent of motor development in children with SMA. OBJECTIVE The aim of the study is to compare NEUROEQUIP-SMA with standard physiotherapy and to evaluate its effect on functional outcomes and quality of life. In addition, the response of molecular biomarkers, such as long non-coding RNAs (lncRNAs), to treatment will be monitored. METHODS In this randomized, assessor-blinded controlled trial (NCT05341453), 16 children with SMA types I–III (aged 2–9 years) will be divided into two groups. Both groups will undergo a 6-day therapeutic program of equal duration and intensity. The intervention group will undergo NEUROEQUIP-SMA therapy, the control group will undergo standard physiotherapy, and both groups will undergo therapeutic grooming. Primary outcomes include motor coordination measured using 3D motion analysis, the presence of muscle fatigue (using surface EMG), spirometry, standardized tests and scaling tests. Secondary outcomes include monitoring of children's psychomotor development (home video analysis) and quality of life (the International Classification of Functioning, Disability and Health-based Documentation Form for the category "Children with Cerebral Palsy Brief”). LncRNAs will be analyzed from blood samples. Statistical analysis will be performed in R software. The study was approved by the Ethics Committee of the Third Faculty of Medicine, Charles University (ref.: 24.2.2022 and 6.3.2023). Informed consent was obtained from the legal representatives of the participants. RESULTS The study was initially designed for 8 participants. Data collection began in April 2022 and was completed in October 2024. Data analyses are planned for autumn 2025. Study results are expected to be available in 2026. The study is anticipated to be fully completed by the end of 2026. CONCLUSIONS This trial will be the first study to evaluate the effects of an equine-assisted physiotherapy intervention based on neuro-proprioceptive principles in children with SMA. If the intervention proves effective, it could expand physiotherapy options for this new generation of children receiving genetic therapies. It is also expected that the results of this study may contribute to the optimization of rehabilitation strategies that integrate biomechanical, clinical, and molecular perspectives. CLINICALTRIAL ClinicalTrials.gov NCT05341453; https://clinicaltrials.gov/study/NCT05341453.

Objectives: To describe longitudinal changes in functional performance, movement quality, respiratory function, and exploratory biological changes during intensive rehabilitation based on neuroproprioceptive “facilitation and inhibition” principles in a child with spinal muscular atrophy (SMA). Methods: This case report describes a girl with SMA type II receiving disease-modifying therapy, including gene therapy, who completed three intensive rehabilitation programs based on neuroproprioceptive “facilitation and inhibition” principles, alternating equine-assisted and individualized outpatient physiotherapy. Clinical, biomechanical, respiratory, and functional outcomes were assessed before and after each therapeutic block. Exploratory molecular analyses were performed only during the second and third programs. International Classification of Functioning, Disability and Health (ICF)-based documentation and home video recordings were obtained before each rehabilitation program and 28 days after completion. Results: Following rehabilitation, improvements were observed in cervical muscle endurance, gross motor function, upper-limb movement quality, spontaneous motor activity, and functional independence. After two rehabilitation blocks, the child successfully performed expiratory maneuvers yielding numerical spirometric results, although the absence of baseline values precluded quantification of changes in respiratory function. The Expanded Hammersmith Functional Motor Scale score increased from 48 to 54 points. The primary outcome, the standard Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score, remained at its maximum of 64/64 throughout. This persistent ceiling effect precluded detection of further changes using the standard score. Three-dimensional motion analysis documented changes consistent with movement goals defined from the pre-intervention clinical assessment, particularly after Equine-Assisted Physiotherapy based on Neuroproprioceptive “Facilitation and Inhibition” (NEUROEQUIP-SMA). Exploratory analysis of peripheral blood long non-coding RNA (lncRNA) expression showed variable temporal changes across the rehabilitation periods, the biological significance of which cannot be determined from a single participant. Conclusions: This case illustrates continued motor development and changes in movement quality during intensive rehabilitation following gene therapy in a child with SMA type II. The contribution of physiotherapy cannot be separated from ongoing development and pharmacological treatment effects and warrants further investigation.