Spinal Muscular Atrophy Type 1 Survival Without New Pharmacotherapies: Two Treatment Paradigms.

OBJECTIVES: The aims of the study are to present noninvasive respiratory management outcomes using continuous noninvasive ventilatory support and mechanical in-exsufflation from infancy for spinal muscular atrophy type 1 and to consider bearing on new medical therapies. DESIGN: Noninvasive ventilatory support was begun for consecutively referred symptomatic infants with spinal muscular atrophy type 1 from 1 to 10 mos of age. Intercurrent episodes of respiratory failure were managed by intubation then extubation to continuous noninvasive ventilatory support and mechanical in-exsufflation despite failing ventilator weaning and extubation attempts. Intubations, tracheotomies, and survival were monitored. RESULTS: Of 153 patients with spinal muscular atrophy 1 consecutively referred since 1995, 37 became continuous noninvasive ventilatory support dependent, almost half before 10 yrs of age. Of the 37, 18 required continuous noninvasive ventilatory support for a mean 18.6 ± 3.3 yrs to a mean 25.3 (range, 18-30) yrs of age, dependent from as young as 4 mos of age with 0 to 40 ml of vital capacity. One of the 18 died from COVID-19 acute respiratory distress syndrome at age 24 after 23 yrs of continuous noninvasive ventilatory support. Extubation success rate of 85% per attempt (150/176) resulted in only one undergoing tracheotomy. CONCLUSIONS: Medical treatments begun during the first 6 wks of age convert spinal muscular atrophy 1 into spinal muscular atrophy 2 or 3 but cough flows remain inadequate to avoid many pneumonias that, once resolved by a treatment paradigm of extubation to continuous noninvasive ventilatory support and mechanical in-exsufflation, eliminates need to resort to tracheotomies.

Successful treatment of respiratory failure in Hirayama disease.

Hirayama disease is a self-limiting cervical motor neuron disease, usually affecting the spinal cord at level C7-T1. We share an unusual case of Hirayama disease in a young man affecting roots C4-C6. He presented in coma due to diaphragm weakness and hypercapnic respiratory failure. Diagnosis was achieved via clinical presentation, neurophysiological examination, ultrasonography of the diaphragm and dynamic MR-imaging. Conservative treatment with a cervical collar resulted in remarkable improvement in respiratory and motor function.

Malnutrition in Spinal Muscular Atrophy Type I: Case Report of a Novel Nutritional Intervention With Improved Growth and Function While Receiving Parallel Gene Splicing Therapies.

Children with spinal muscular atrophy (SMA) frequently experience feeding intolerance and diminished growth. Although splicing modulators to prevent symptoms are available worldwide, adequate nutrition to support growth, development, and improved quality of life remains essential. We present a case study of a one-year-old malnourished male with SMA type I who achieved improved growth and feeding tolerance with a human milk (HM)-derived nutrition intervention. Despite feeding with appropriately balanced semielemental formula, he remained severely malnourished after two months of hospitalization. Feeds were partially replaced with HM-based diet plus a HM-based fat modular. Feeding tolerance, fecal calprotectin levels, and z scores for weight and length improved while receiving the HM-based intervention. We hypothesize that the HM-based feeding reduced intestinal inflammation by diminishing pathogenic elements of his microbiome. Owing to their aberrant fatty acid metabolism, patients with SMA are uniquely positioned to benefit from HM-based nutrient acquisition even while receiving splicing modulators to stabilize the disease process.

Pregnancy experience in women with spinal muscular atrophy: a case series.

Many women with spinal muscular atrophy (SMA) types II, III, and IV reach fertile age, and some of them may consider pregnancy. However, limited data are available about the potential effects of pregnancy on the course of SMA and the outcomes of pregnancies in these patients. Furthermore, the use of several disease-modifying therapies for the treatment of all types of SMA is expected to increase the number of female SMA patients considering pregnancy in the coming years. The aim of this report is to provide clinicians with an overview of the patients in our cohort who have experienced pregnancies. We conducted a retrospective analysis on these women, through the administration of a questionnaire, which investigated how they experienced the different stages of the pregnancy. Ten patients (3 SMAII; 7 SMA III) participated in the survey; 40% had pregnancies for a total of nine, six of which were term-pregnancies. The mean age of first pregnancy was 32.5 ± 7.8 years for SMA II patients, and 30.5 ± 2.1 years for SMA III. All pregnancies ended in cesarean sections. Interestingly, the sitters had more frequent complications in pre-term labor and delivery, but the newborns were all healthy. This report shows that a successful pregnancy is possible in female patients with SMA. However, the ideal approach should involve a standardized multidisciplinary team capable of effectively addressing every possible scenario. For this reason, it is critically important that clinicians working with SMA patients gain more in-dept knowledge about this topic.

Sleep disordered breathing in infants identified through newborn screening with spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) is a genetic disorder that may result in neuromuscular weakness and respiratory insufficiency. Gene replacement therapy has changed the trajectory of this condition, but long-term outcomes related to sleep disordered breathing are not known. METHODS: This was a retrospective review of infants with SMA identified via newborn screening who subsequently received onasemnogene abeparvovec at the Hospital for Sick Children (Ontario, Canada). Polysomnograms were conducted at the time of confirmed diagnosis as well as regularly thereafter. RESULTS: Eleven children (4 female) were identified via newborn screen (7 with 2 copies of the SMN2 gene and 4 with 3 copies of the SMN2 gene) and received onasemnogene abeparvovec at a median age of 3.6 weeks. All eleven infants met criteria for sleep disordered breathing based on their first completed polysomnograms but improved over time. Three infants required respiratory technology, including a premature infant who was prescribed nocturnal supplemental oxygen therapy for central sleep apnea and two symptomatic infants with neuromuscular weakness who required nocturnal noninvasive ventilation. We did not find a correlation between motor scores and polysomnogram parameters. CONCLUSION: Children treated with onasemnogene abeparvovec have reduced sleep disordered breathing over time. Polysomnograms revealed abnormal parameters in all children, but the clinical significance of these findings was unclear for children who were asymptomatic for sleep disordered breathing or neuromuscular weakness. These results highlight the need to evaluate both motor scores and respiratory symptoms to ensure a holistic evaluation of clinical status.

Gene transfer therapy in children with spinal muscular atrophy: A single-center experience with a cohort of 25 children.

INTRODUCTION/AIMS: New therapeutic strategies to increase survival motor neuron protein levels in spinal muscular atrophy (SMA) have focused on replacing the SMN1 gene. Onasemnogene abeparvovec was approved by the US Food and Drug Administration in 2019 for treatment of children with SMA less than 2 years of age. Postmarketing studies are limited, especially outside of Europe and the United States. Herein we describe a single-center experience with onasemnogene abeparvovec from the Middle East. METHODS: Between November 17, 2020 and January 31, 2022, 25 children with SMA received onasemnogene abeparvovec at our center in the United Arab Emirates. Data were collected on patients' demographics, age at diagnosis, SMA type, genetic information, relevant medical history, laboratory investigations, and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) functional assessment scores at baseline and 1 and 3 months after gene therapy. RESULTS: Onasemnogene abeparvovec was well tolerated. Significant improvements in CHOP-INTEND scores were observed after the therapy. Elevation of liver enzymes and thrombocytopenia were the most common adverse events, but were transient and managed with high-dose corticosteroids. There were no life-threatening adverse events or deaths reported during the 3-month follow-up period. DISCUSSION: The study findings concurred with those of previously published studies. Side effects of gene transfer therapy are well tolerated, although serious complications can arise. In such cases, persistent transaminitis for example, steroid dose escalation is warranted with close observation of the patient's clinical status and lab values. Combination therapy should be explored as an alternative to gene transfer therapy only.

Onasemnogene abeparvovec preserves bulbar function in infants with presymptomatic spinal muscular atrophy: a post-hoc analysis of the SPR1NT trial.

Bulbar function in spinal muscular atrophy has been defined as the ability to meet nutritional needs by mouth while maintaining airway protection and communicate verbally. The effects of disease-modifying treatment on bulbar function are not clear. A multidisciplinary team conducted post-hoc analyses of phase 3 SPR1NT trial data to evaluate bulbar function of infants at risk for spinal muscular atrophy who received one-time gene replacement therapy (onasemnogene abeparvovec) before symptom onset. Three endpoints represented adequate bulbar function in SPR1NT: (1) absence of physiologic swallowing impairment, (2) full oral nutrition, and (3) absence of adverse events indicating pulmonary instability. Communication was not assessed in SPR1NT. We descriptively assessed numbers/percentages of children who achieved each endpoint and all three collectively. SPR1NT included infants <6 postnatal weeks with two (n = 14) or three (n = 15) copies of the survival motor neuron 2 gene. At study end (18 [two-copy cohort] or 24 [three-copy cohort] months of age), 100% (29/29) of patients swallowed normally, achieved full oral nutrition, maintained pulmonary stability, and achieved the composite endpoint. When administered to infants before clinical symptom onset, onasemnogene abeparvovec allowed children at risk for spinal muscular atrophy to achieve milestones within published normal ranges of development and preserve bulbar function.

Barriers and facilitating factors of care coordination for children with spinal muscular atrophy type I and II from the caregivers' perspective: an interview study.

BACKGROUND: Children with medical complexity (CMC) require long-term care accompanied by different health- and social care professionals. Depending on the severity of the chronic condition, caregivers spend a lot of time coordinating appointments, communicating between providers, clarifying social legal issues, and more. Effective care coordination is seen as key to addressing the fragmented care that CMC and their families often face. Spinal muscular atrophy (SMA) is a rare genetic, neuromuscular disease which care involves drug therapy and supportive treatment. We examined the care coordination experiences through a qualitative interview analysis of n = 21 interviews with caregivers of children with SMA I or SMA II. RESULTS: The code system consists of 7 codes and 12 sub-codes. "Disease and coordination management of the caregivers" describes the management of coordination-related illness demands. "General conditions of care" include enduring organizational aspects of the care network. "Expertise and skills" refers to both parent and professional expertise. "Coordination structure" describes the assessment of existing coordination mechanisms as well as the need for new ones. "Information exchange" defines the information exchange between professionals and parents as well as the exchange of parents among themselves and the perceived exchange between professionals. "Role distribution in care coordination" summarizes parents' "distribution" of coordinative roles among care network actors (including their own). "Quality of relationship" describes the perceived quality of the relationship between professionals and family. CONCLUSION: Care coordination is influenced peripherally (e.g., by general conditions of care) and directly (e.g., by coordination mechanisms, interaction in the care network). Access to care coordination appears to be dependent on family circumstances, geographic location, and institutional affiliation. Previous coordination mechanisms were often unstructured and informal. Care coordination is frequently in the hands of caregivers mainly as the care network's interface. Coordination is necessary and must be addressed on an individual basis of existing resources and family barriers. Existing coordination mechanisms in the context of other chronic conditions could also work for SMA. Regular assessments, centralized shared care pathways, and staff training and empowerment of families for self-management should be central components of all coordination models. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00018778; Trial registration date 05. December 2019-Retrospectively registered; https://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00018778 .

Real-Life Outcome After Gene Replacement Therapy for Spinal Muscular Atrophy: A Multicenter Experience.

BACKGROUND: Onasemnogene abeparvovec-xioi (OA) has been available since 2019 as a gene replacement therapy for individuals with spinal muscular atrophy (SMA) under age two years. We aim to expand upon the sparse knowledge about its safety and clinical efficacy. METHODS: The clinical outcome data of all the individuals with SMA who were treated with gene therapy in four tertiary hospitals in Israel were retrieved and analyzed. RESULTS: The study participants included 25 individuals who received the gene therapy between age 11 days and 23 months and whose median follow-up duration was 18.0 (interquartile range [IQR], 12.4 to 18.3) months. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores increased by a median (IQR) of 13 (8 to 20) points at the last follow-up compared with baseline. None of the patients experienced regression in motor abilities after gene therapy, which was generally well tolerated. There was gradual improvement in motor function, especially among presymptomatic patients (P ≤ 0.001) whose disease duration was shorter (≤8 months) before receiving gene therapy (P ≤ 0.001) and who did not experience recurrent infections and illnesses in the months following treatment (P ≤ 0.001). CONCLUSIONS: OA was well tolerated and led to favorable functional motor outcomes at six to 24 months after treatment initiation. Better progress in motor function was observed in individuals who received OA earlier and who were presymptomatic, irrespective of the SMN2 copy number or type. Our results further strengthen the clinical efficacy of OA and reinforce the importance of early recognition of SMA via newborn screening programs.

Necrotizing Enterocolitis following Onasemnogene Abeparvovec for Spinal Muscular Atrophy: A Case Series.

Onasemnogene abeparvovec treats spinal muscular atrophy by delivering a functional SMN1 gene. Necrotizing enterocolitis typically occurs in preterm infants. We report 2 term infants diagnosed with spinal muscular atrophy who presented with necrotizing enterocolitis after onasemnogene abeparvovec infusion. We discuss potential etiologies and propose monitoring for necrotizing enterocolitis after onasemnogene abeparvovec therapy.

Intrathecal Onasemnogene Abeparvovec for Sitting, Nonambulatory Patients with Spinal Muscular Atrophy: Phase I Ascending-Dose Study (STRONG).

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disorder arising from biallelic non-functional survival motor neuron 1 (SMN1) genes with variable copies of partially functional SMN2 gene. Intrathecal onasemnogene abeparvovec administration, at fixed, low doses, may enable treatment of heavier patients ineligible for weight-based intravenous dosing. OBJECTIVE: STRONG (NCT03381729) assessed the safety/tolerability and efficacy of intrathecal onasemnogene abeparvovec for sitting, nonambulatory SMA patients. METHODS: Sitting, nonambulatory SMA patients (biallelic SMN1 loss, three SMN2 copies, aged 6-<60 months) received a single dose of intrathecal onasemnogene abeparvovec. Patients were enrolled sequentially into one of three (low, medium, and high) dose cohorts and stratified into two groups by age at dosing: younger (6-<24 months) and older (24-<60 months). Primary endpoints included safety/tolerability, independent standing ≥3 seconds (younger group), and change in Hammersmith Functional Motor Scale Expanded (HFMSE) from baseline (older group) compared with historic controls. RESULTS: Thirty-two patients were enrolled and completed the study (medium dose, n = 25). All patients had one or more treatment-emergent adverse events, with one serious and related to treatment (transaminase elevations). No deaths were reported. One of 13 patients (7.7%) in the younger group treated with the medium dose achieved independent standing. At Month 12 for the older group receiving the medium dose, change from baseline in HFMSE was significantly improved compared with the SMA historic control population (P < 0.01). CONCLUSIONS: Intrathecal onasemnogene abeparvovec was safe and well-tolerated. Older patients treated with the medium dose demonstrated increases in HFMSE score greater than commonly observed in natural history.

Evaluation of sputum cultures in children with spinal Muscular atrophy.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a severe neuromuscular disorder. Despite increased survival due to novel therapies, morbidity from respiratory complications still persists. We aim to describe these patients' sputum cultures as an expression of chronic infectious airway disease. METHODS: Retrospective review of medical records of all children with SMA followed at the multidisciplinary respiratory neuromuscular clinic at Schneider Childrens' Medical Center of Israel over a 16-year period. Sputum cultures were obtained during routine visits or pulmonary exacerbations. RESULTS: Sixty-one SMA patients, aged 1 month to 21 years, were included in this cohort. Of these, sputum cultures were collected from 41 patients. Overall, 288 sputum cultures were obtained, and 98 (34%) were negative for bacterial growth. For the first culture taken from each patient, 12 out of 41 (29%) were sterile. The most common bacteria were pseudomonas aeruginosa (PSA) (38%) and staphylococcus aureus (19.6%). PSA was found in SMA type I patients more frequently than in type II patients (15/26 = 58% vs 4/13 = 31%, p < 0.001). PSA infection was positively associated with noninvasive ventilation, recurrent atelectasis, recurrent pneumonias, swallowing difficulties, but no significant association was found with cough assist machine usage. The incidence of positive cultures did not differ between those treated with Onasemnogene abeparvovec or Nusinersen compared to those without treatment, but the age of first PSA isolation was slightly older with Nusinersen treatment (p = 0.01). CONCLUSIONS: Airway bacterial colonization is common in SMA type I patients and is not decreased by Onasemnogene abeparvovec or Nusinersen treatment.

A breakthrough effect of gene replacement therapy on respiratory outcomes in children with spinal muscular atrophy.

INTRODUCTION: Spinal muscular atrophy (SMA) is an inherited progressive neuromuscular disorder characterized by generalized hypotonia, respiratory failure and early death. The introduction of gene replacement therapy (GRT) modified the natural history of the disease. However, more data is needed to understand the long-term effect of GRT on measurable respiratory outcomes. We report the respiratory outcomes in our cohort of patients with SMA post-GRT in 2-year period. METHODS: A retrospective chart-review of genetically confirmed children with SMA who received GRT between 2019 and 2021 in Qatar. The evaluated respiratory outcomes were chronic respiratory support, respiratory hospitalizations, escalation of respiratory support and polysomnography results before and after GRT. Nonrespiratory outcomes; nutritional status, swallowing, and motor functions; were also assessed. RESULTS: A total of 11 patients (9 patients with SMA-1 and 2 patients with SMA-2) received GRT at a median age of 12 months and 22 months in patients with SMA-1 and SMA-2, respectively. All patients were successfully weaned off Noninvasive ventilation (NIV) except one patient who remained on mechanical ventilation through tracheostomy tube. The annualized hospitalization rate dropped by half after GRT. The average length of stay (LOS) in intensive care unit (ICU) decreased by 17.32 days/patient/year after GRT. Duration of required escalation of respiratory support during acute hospitalizations has dropped by 18.56 days/patient/year post-GRT. CONCLUSION: We report favorable respiratory outcomes of GRT in our cohort. GRT resulted in discontinuation of chronic respiratory support in majority of ventilated patients. GRT also resulted in decreased respiratory hospitalization rate, hospital-LOS, ICU-LOS, and need for escalation of ventilatory support.

Disease Burden in Children With Spinal Muscular Atrophy: Results From a Large Cross-Sectional Study.

Background:To facilitate advances in spinal muscular atrophy therapeutic research, it is important to determine the impact and prevalence of symptoms experienced by children with spinal muscular atrophy. Methods: We conducted qualitative interviews with caregivers of children with spinal muscular atrophy. From these interviews, we generated a survey inquiring about 260 symptoms of importance grouped into 17 symptomatic themes. Results: Sixteen caregivers of children with spinal muscular atrophy aged from 4 months to 12 years participated in initial interviews, and 77 caregivers completed the survey. Higher symptom prevalence was associated with spinal muscular atrophy type, SMN2 copy number, and functional status. Hip, thigh, or knee weakness had the greatest reported impact on the lives of children with spinal muscular atrophy. Conclusions: This research provides one of the largest data sets regarding disease burden in children with spinal muscular atrophy. The most prevalent symptoms are not identical to those with the greatest impact. This unique insight into the most impactful symptoms will help focus therapeutic development in spinal muscular atrophy.

Prevalence of Spinal Muscular Atrophy in the Era of Disease-Modifying Therapies: An Italian Nationwide Survey.

OBJECTIVE: Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene. The aim of this study was to assess the prevalence of SMA and treatment prescription in Italy. METHODS: An online survey was distributed to 36 centers identified by the Italian government as referral centers for SMA. Data on the number of patients with SMA subdivided according to age, type, SMN2 copy number, and treatment were collected. RESULTS: One thousand two hundred fifty-five patients with SMA are currently followed in the Italian centers with an estimated prevalence of 2.12/100,000. Of the 1,255, 284 were type I, 470 type II, 467 type III, and 15 type IV with estimated prevalence of 0.48, 0.79, 0.79 and 0.02/100,000, respectively. Three patients with SMA 0 and 16 presymptomatic patients were also included. Approximately 85% were receiving one of the available treatments. The percentage of treated patients decreased with decreasing severity (SMA I: 95.77%, SMA II: 85.11%, SMA III: 79.01%). DISCUSSION: The results provide for the first time an estimate of the prevalence of SMA at the national level and the current distribution of patients treated with the available therapeutical options. These data provide a baseline to assess future changes in relation to the evolving therapeutical scenario.

Spinal muscular atrophy in Ghanaian children confirmed by molecular genetic testing: a case series.

Spinal muscular atrophy (SMA) is an autosomal recessive inherited motor neuron disease characterized by progressive muscle weakness due to degeneration and loss of the anterior horn cells in the spinal cord and the brain stem nuclei from foetal life through infancy and childhood. SMA is prevalent in Ghanaian children, though not widely reported. Cases are likely missed or misdiagnosed due to lack of expertise and investigations. Newborn screening is not currently available in Ghana. The management remains supportive as newly approved genetic modifications therapies are currently not available. We present a retrospective folder review of children attending a tertiary pediatric neurology clinic who were diagnosed with SMA and confirmed by molecular genetic testing. Between January 2018 and August 2021, five (5) children from three families had molecular genetic tests confirming their diagnosis of SMA. Three (3) children had SMA I phenotype while 2 had SMA III phenotype. Two (2) of the 3 children with SMA I died from respiratory complications. The last surviving child with SMA I was diagnosed through newborn screening program overseas and received gene modification therapy. Careful history and physical examination remain the best approach to diagnosis as confirmatory genetic testing and supplemental investigations are not readily available. The current management of the children with SMA in Ghana include respiratory care, physiotherapy, and genetic counselling. Genetic modification therapies are currently not available.

Bridging the Gap: Gene Therapy in a Patient With Spinal Muscular Atrophy Type 1.

Molecular therapies exploit the understanding of pathogenic mechanisms to reconstitute impaired gene function or manipulate flawed RNA expression. These therapies include (1) RNA interference by antisense oligonucleotides, (2) mRNA modification using small molecules, and (3) gene replacement therapy, the viral-mediated intracellular delivery of exogenous nucleic acids to reverse a genetic defect. Several molecular therapies are approved for treating spinal muscular atrophy (SMA), a recessive genetic disorder caused by survival motor neuron (SMN)1 gene alterations. SMA involves degeneration of lower motor neurons, which leads to progressive muscle weakness, hypotonia, and hypotrophy. Onasemnogene abeparvovec is a gene replacement therapy for SMA that uses adeno-associated virus delivery of functional SMN1 cDNA to motor neurons. Two other molecular therapies modulate SMN2 transcription: nusinersen, an antisense oligonucleotide, and risdiplam, a small molecule designed to modify faulty mRNA expression. The most suitable individualized treatment for SMA is not established. Here, we describe remarkable clinical improvement in a 4-month-old patient with SMA type 1 who received onasemnogene abeparvovec therapy. This case represents an explanatory bridge from bench to bedside with regard to therapeutic approaches for genetic disorders in neurology. Knowledge of the detailed mechanisms underlying genetic neurologic disorders, particularly monogenic conditions, is paramount for developing tailored therapies. When multiple disease-modifying therapies are available, early genetic diagnosis is crucial for appropriate therapy selection, highlighting the importance of early identification and intervention. A combination of drugs, each targeting unique genetic pathomechanisms, may provide additional clinical benefits.

[Access to orphan drugs for the treatment of spinal muscular atrophy in Spain]. / Acceso a medicamentos huérfanos para el tratamiento de la atrofia muscular espinal en España.

INTRODUCTION: Spinal muscular atrophy (SMA) is a rare disease whose diagnosis and treatment are complex. In Spain, there are two orphan medicines that are currently financed by the state, nusinersen and onasemnogene abeparvovec and, a third in process, risdiplam. The objective was to detect possible causes of inequity in the diagnosis and treatment of SMA in Spain. MATERIALS AND METHOD: Descriptive study realized in two phases: a first phase of bibliographic revision and a second phase of semi-structured interviews with clinical experts in SMA in Andalusia, Castilla-La Mancha, Catalonia and Murcia. RESULTS: The number of centers, services or units of reference, the availability of regional autonomous plans for rare diseases and pilot programs of neonatal screenings can regulate access to treatments. The number of new patients diagnosed per year is estimated between one and six in the four autonomous communities (ACs) of Spain studied. Differences were not found in logistical resources. Two of the four ACs studied have regional autonomous plans for rare diseases, however, their utility has only had relevance in one of two of the ACs. CONCLUSIONS: Important differences in access to nusinersen were not identified in the studied ACs The diagnosis of SMA requires clinical specialized experts and specialized centers for early intervention of disease-modifying therapies.

TITLE: Acceso a medicamentos huérfanos para el tratamiento de la atrofia muscular espinal en España.Introducción. La atrofia muscular espinal (AME) es una enfermedad rara cuyo diagnóstico y tratamiento es complejo. En España hay dos medicamentos huérfanos financiados por el Sistema Nacional de Salud, nusinersén y onasemnogén abeparvovec, y un tercero, risdiplam, pendiente. El objetivo fue analizar el acceso a los fármacos modificadores de la AME y detectar posibles causas de inequidad. Materiales y método. Estudio descriptivo realizado en dos fases: revisión bibliográfica y entrevistas semiestructuradas a expertos clínicos en AME de las comunidades autónomas (CC. AA.) de Andalucía, Castilla-La Mancha, Cataluña y Murcia. Resultados. El número de centros, servicios o unidades de referencia, la disponibilidad de planes autonómicos para enfermedades raras y los programas piloto de cribado neonatal pueden modular el acceso a los nuevos tratamientos farmacológicos. El número de nuevos pacientes diagnosticados al año se estimó entre uno y seis en cada una de las CC. AA. estudiadas. Dos de las cuatro CC. AA. estaban participando en ensayos clínicos. El tiempo desde la prescripción a la administración de nusinersén estaba entre siete y 60 días. Sólo Cataluña comunicó experiencia con onasemnogén abeparvovec a 30 de junio de 2022. Dos CC. AA. de las cuatro estudiadas disponen de plan autonómico para enfermedades raras; no obstante, se identificó como relevante para el tratamiento de la AME sólo en una de ellas. Conclusiones. No se identificaron diferencias importantes en el acceso al nusinersén en las CC. AA. estudiadas. El diagnóstico de la AME requiere personal clínico experto y centros especializados para iniciar precozmente los tratamientos modificadores de la enfermedad.