Intrathecal delivery of nusinersen using the Ommaya reservoir in a spinal muscular atrophy type 2 patient: a case report / 中华神经科杂志

Ommaya reservoir implantation is generally used in the treatment of hydrocephalus and intraventricular drug administration. Ommaya reservoir implantation in the subarachnoid space of the spinal cord for the intrathecal drug administration has not been carried out in China, and only several reports can be retrieved from PubMed. About 60%-90% of untreated patients with spinal muscular atrophy type 2 (SMA2) who survive to adulthood often have complex scoliosis and joint deformities. Nusinersen is an effective drug for the treatment of SMA2. And the route of administration is intrathecal injection, which is difficult for patients with severe scoliosis. This article summarizes the process of Ommaya reservoir implantation and postoperative drug administration in a patient with complex scoliosis type SMA2, which provides a new method for clinical treatment of this disease.

Improvement of Motor and Life Functions after Nusinersen Treatment in an Adult Patient with Spinal Muscular Atrophy Type II / The Japanese Journal of Rehabilitation Medicine

Spinal muscular atrophy is a neuromuscular disease characterized by muscle atrophy and progressive muscle weakness due to the degeneration of motor neurons in the anterior horn of the spinal cord. We report a case of an adult patient with spinal muscular atrophy type II and difficulty holding a sitting position. The patient was evaluated before and after Nusinersen treatment and thereafter periodically for up to 3 months for motor and daily living functions. At 3 months post-treatment, the Expanded version of the Hammersmith Functional Motor Scale and the Revised Upper Limb Module, which are motor function assessment tools for evaluating spinal muscular atrophy, showed an increase of 2 points. Evaluation of daily functioning using the Canadian occupational performance measure demonstrated improvements in eating and computer finger manipulation, and these improvements were considered important in daily lives by the patient. This report shows that the Nusinersen treatment improved motor and daily life functions in a patient with spinal muscular atrophy and low motor function. The report also concludes that rehabilitation evaluation for spinal muscular atrophy should include a disease-specific assessment of motor function, combined with an assessment focusing on physical symptoms and daily life functions to capture clinical changes that are responsive to individual patients with spinal muscular atrophy.

Nusinersen treatment in patients with spinal muscular atrophy: A safety analysis of laboratory parameters / 西安交通大学学报(医学版)

【Objective】 To explore the changes of laboratory parameters and safety of nusinersen in the treatment of spinal muscular atrophy (SMA). 【Methods】 Retrospective analysis was made on the six SMA patients treated with nusinersen in the Department of Neurology at The First Affiliated Hospital of Xi’an Jiaotong University from December 2021 to December 2022. We summarized the patients’ clinical data, including genetic diagnosis results, disease classification, and clinical manifestations. Intrathecal injection of 5 mL/12 mg of nusinersen administered on the 1st, 14th, 28th, and 63rd days, followed by maintenance treatment every 4 months. After each administration, we compared and evaluated the patients’ cerebrospinal fluid, blood routine, liver function, kidney function, and coagulation function with baseline values. We regularly followed up the patients and recorded adverse reactions after administration to evaluate medication safety. 【Results】 A total of six patients were diagnosed with SMA, including four cases of SMA3 type and two cases of SMA4 type. The deletion of exon 7 of the survival motor neuron gene 1 (SMN1) in patients led to changes in motor neuron, most of which were caused by limb weakness; in severe cases, the patients were unable to stand. The baseline abnormal test indicators of patients included the increase of cerebrospinal fluid lactate dehydrogenase (CSF-LDH), the increase of creatine kinase (CK), and the decrease of creatinine (Cr). After four times of treatment, the patients’ CSF-WBC, CSF-Glu, CSF-Pro, CSF-LDH, WBC, PLT, RBC, ALT, AST, GGT, BUN, uric acid (UA), INR, aPTT, and D-dimer had no significant difference from the baseline (P>0 05). The patients had no other significant adverse reactions except headaches, dizziness, and back pain after puncture. 【Conclusion】 Nusinersen has good safety on SMA patients.

Improvement of Motor and Life Functions after Nusinersen Treatment in an Adult Patient with Spinal Muscular Atrophy Type II / The Japanese Journal of Rehabilitation Medicine

Spinal muscular atrophy is a neuromuscular disease characterized by muscle atrophy and progressive muscle weakness due to the degeneration of motor neurons in the anterior horn of the spinal cord. We report a case of an adult patient with spinal muscular atrophy type II and difficulty holding a sitting position. The patient was evaluated before and after Nusinersen treatment and thereafter periodically for up to 3 months for motor and daily living functions. At 3 months post-treatment, the Expanded version of the Hammersmith Functional Motor Scale and the Revised Upper Limb Module, which are motor function assessment tools for evaluating spinal muscular atrophy, showed an increase of 2 points. Evaluation of daily functioning using the Canadian occupational performance measure demonstrated improvements in eating and computer finger manipulation, and these improvements were considered important in daily lives by the patient. This report shows that the Nusinersen treatment improved motor and daily life functions in a patient with spinal muscular atrophy and low motor function. The report also concludes that rehabilitation evaluation for spinal muscular atrophy should include a disease-specific assessment of motor function, combined with an assessment focusing on physical symptoms and daily life functions to capture clinical changes that are responsive to individual patients with spinal muscular atrophy.

Case report of gene therapy and nursing care for children with type Ⅱ spinal muscular atrophy / 中国实用护理杂志

Objective:To summarize the nursing care of 3 cases of spinal muscular atrophy (SMA) with intrathecal injection of Nusinersen sodium injections.Methods:From March 2020 to March 2021, 3 children patients with SMA received Nusinersen sodium injections. Multidisciplinary care was applied, the key points of nursing care include: multidisciplinary individualized assessments, multidisciplinary care based on case management model, preoperative and intraoperative care cooperation, and postoperative observations and management of complications.Results:All the three children successfully completed intrathecal injection and were discharged on the second day after surgery. No serious complications occurred.Conclusions:Collaborative multidisciplinary care shows positive significance for children with intrathecal Nusinersen sodium injections.

Advances in drugs on targeting SMN2 for the treatment of spinal muscular atrophy / 药学学报

As one of the most serious hereditary neuromuscular disease, spinal muscular atrophy (SMA) is caused by the loss or mutation of survival motor neuron 1 (SMN1) gene. It leads to a decrease in the level of SMN protein and a consequent loss of alpha neurons and progressive muscle atrophy resulting in the progressive muscle weakness, the significant disability and the shortened lifespan. Up till now, only three drugs have been approved for SMA, including the gene therapy drug onasemnogene abeparvovec. The antisense oligonucleotide drug nusinersen and and the small molecule chemical drug risdiplam were briefly introduced. Some representative samples of the small molecule chemical drugs and antisense oligonucleotide drugs targeting SMN2 in the clinical trial or preclinical research phases were also reviewed.

Anestesia para colocación de nusinersen intratecal en pacientes con atrofia muscular espinal / Anesthesia for instillation of intratecal nusinersen in patients for muscular atrophy

We present a series of four patients diagnosed with Spinal Muscular Atrophy (SMA), 2 type II, 2 type III, for placement of spinal nusinersen/Spinraza under general anesthesia with propofol. This new treatment can improve the quality of life of these patients. Its management represents a challenge for anesthesiologists as they try to provide not only adequate general anesthesia but containment to adolescent or young patients. In particular, patients that need to enter into the operating room several times a year.

Presentamos una serie de 4 pacientes con diagnóstico de atrofia muscular espinal (AME) 2 tipo II y 2 tipo III, para colocación de nusinersen/Spinraza raquídeo bajo anestesia general con propofol. Este nuevo tratamiento puede mejorar la calidad de vida de los pacientes. Su manejo representa un desafío para los anestesiólogos que intentamos brindar no solo una adecuada anestesia general sino contención a pacientes adolescentes o jóvenes que necesitan ingresar al quirófano varias veces al año.

Antisense Oligonucleotides: A Unique Treatment Approach

Synthetic Antisense oligonucleotides (ASOs) are novel and efficient laboratory tools to regulate the expression of specific genes, andhave only recently come into clinical use. These are synthetic single-stranded DNA analogs, whose sequence is complementary to atarget nucleotide and alter protein synthesis by several mechanisms. We herein provide a primer on the topic for pediatricians, as thisgroup of drugs is likely to see many more drugs for previously incurable diseases.

Nusinersen as a Therapeutic Agent for Spinal Muscular Atrophy

The reduction of survival motor neuron (SMN) protein causes spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease. Nusinersen is an antisense oligonucleotide, approved by the FDA, which specifically binds to the repressor within SMN2 exon 7 to enhance exon 7 inclusion and augment production of functional SMN protein. Nusinersen is the first new oligonucleotide-based drug targeting the central nervous system for the treatment of SMA. This review of nusinersen will discuss its action mechanism, cellular uptake, trafficking mechanisms, and administration approaches to cross the blood-brain barrier. Furthermore, nusinersen clinical trials will be assessed in terms of pharmacokinetics, tolerability and safety, the clinical outcomes of multiple intrathecal doses, and a discussion on the primary and secondary endpoints.

Manejo respiratorio en atrofia muscular espinal: cambio de paradigma en la era de las nuevas terapias específicas / Respiratory care in spinal muscular atrophy in the new therapeutic era

Resumen: La atrofia muscular espinal (AME) es la enfermedad genética mortal más frecuente en lactantes, con severidad variable. Se clasifica en cuatro subtipos: tipo 0 de inicio prenatal y recién nacido ya afecta do, con ausencia de esfuerzo respiratorio y ningún desarrollo motor, tipo 1 de inicio en menores de 3 meses que no logran sentarse, tipo 2 que logran sentarse, pero no caminar y tipo 3 que consiguen caminar. La causa más seria de morbimortalidad es la neumonía y la insuficiencia respiratoria. La información a los cuidadores debe contemplarse desde el diagnóstico, para la toma de decisiones anticipadas. Los objetivos del manejo incluyen el estímulo de la tos, evitar la deformación de la caja torácica, la hipoventilación, y tratar oportunamente las infecciones respiratorias, el trastorno de de glución, el reflujo gastroesofágico y la malnutrición. El objetivo de esta actualización es discutir los nuevos desafíos en cuidados respiratorios con un enfoque preventivo, considerando la reciente dis ponibilidad de tratamientos específicos -oligonucleótidos antisentido nusinersen- y otros que están en desarrollo, incluída la terapia génica.

Abstract: Spinal muscular atrophy (SMA) is the first inherited cause of mortality in infants, with four subtypes: SMA0 prenatal onset, SMA1 babies less than 3 months non sitters, SMA2 sitters and SMA3 walkers. Pneumonia and respiratory insufficiency are the most severe complications. Informed parental de cisions are relevant. Respiratory management includes cough assistance, prevention of lung under development due to chest deformity, prompt treatment of respiratory infections, hypoventilation, swallow problems, gastro esophageal reflux and malnutrition. In view of the FDA and EMA approval of the nonsense oligonucleotides nusinersen, the first specific treatment for SMA and the future with gene therapy and others under development, we need to optimize preventive respiratory manage ment with the new standard of care.