Materiały źródłowe

• #1 Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10605203/

  Spinal muscular atrophy (SMA) is a rare neuromuscular disease, with an estimated incidence of about 1 in 10,000 live births. To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec, and risdiplam. […] The aim of this narrative review was to provide an overview of the pre- and post-marketing evidence on the pharmacological treatments approved for the treatment of SMA by identifying preclinical and clinical studies registered in clinicaltrials.gov and in the EU PAS register from their inception until the 4 January 2023. […] To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, an antisense oligonucleotide, onasemnogene abeparvovec, a gene therapy, and risdiplam, a SMN2 pre-mRNA splicing small-drug modifier.

• #2 Spinal muscular atrophy (SMA) | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/spinal-muscular-atrophy-sma

  There is no cure for SMA, but there are some promising treatments being tested in clinical trials. […] There is currently no specific treatment for SMA. However, research for a treatment is moving forward at a fast pace. Support is available for children with SMA and their families so they can achieve maximum quality of life. […] In contrast, the care of a child or adult with SMA types 3 or 4 will focus on physiotherapy to help maintain muscle strength and mobility. A multidisciplinary team of healthcare professionals will be needed to manage the symptoms of SMA.

• #3 Spinal Muscular Atrophy (SMA) (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/sma.html

  Spinal muscular atrophy (SMA) is a genetic condition that causes muscle weakness and atrophy (when muscles get smaller). […] All types need ongoing treatment by a medical care team. There’s no cure for SMA, but treatments can help children who have it live a better life. […] There’s no cure for SMA, but a few treatment options are available. What doctors use depends on a child’s age and how severe the symptoms are. […] Treatment options include: […] Disease-modifying therapy: These medicines increase the amount of SMN protein in the body. One medicine, Nusinersen (or Spinraza), is given through a spinal tap. Others can be given by IV infusion or by mouth. […] Gene replacement therapy: This therapy involves replacing the mutated SMN1 gene with a normal SMN1 gene. It is given one time by IV infusion.

• #4 Spinal Muscular Atrophy Treatment – Cure SMA

  https://www.curesma.org/spinal-muscular-atrophy-treatment/

  Regardless of what type of treatment is selected, it is important that individuals with SMA begin therapy as soon after diagnosis as possible. […] Beginning therapy as early as possible is the only way to prevent or slow down motor neuron loss. […] Currently, three SMN-enhancing (SMA) spinal muscular atrophy treatments are approved by the U.S. Food and Drug Administration (FDA).

• #5 SMA (Spinal Muscular Atrophy): What It Is, Symptoms & Types

  https://my.clevelandclinic.org/health/diseases/14505-spinal-muscular-atrophy-sma

  Spinal muscular atrophy (SMA) is a genetic condition that causes worsening muscle weakness. […] Theres no cure for SMA, but certain therapies and medications can help manage symptoms. […] Treatment for SMA mainly seeks to manage symptoms and prevent complications. Symptom management therapies may include: Physical therapy, which can help improve posture, prevent joint immobility and slow muscle weakness. Occupational therapy, which can improve your ability to perform daily tasks. Assistive devices, like orthopaedic braces, crutches, walkers and wheelchairs. Therapy for speech and swallowing difficulties. A feeding tube if swallowing is too difficult and/or dangerous. Assisted ventilation for breathing issues. […] Between 2016 and 2020, the U.S. Food and Drug Administration (FDA) approved treatments that can significantly improve the course of SMA. They include: Disease-modifying therapy: These medications stimulate the production of SMN2 protein. The FDA has approved Nusinersen (Spinraza) for both children and adults. A healthcare provider injects the medication into the space around your spinal canal. A different medication, risdiplam (Evrysdi), helps those with SMA who are 2 months and older. You take risdiplam daily by mouth (orally). Gene replacement therapy: Children younger than 2 may benefit from a one-time intravenous (IV) infusion of a medication called onasemnogene abeparvovec-xioi (Zolgensma). This therapy replaces a missing or faulty SMN1 gene with a functioning gene. […] These newer treatments may be particularly effective if started early, even before symptoms of SMA appear. Given the availability of these treatments, theres now routine screening of newborns for SMA in the United States.

• #6 Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10605203/

  Spinal muscular atrophy (SMA) is a rare neuromuscular disease, with an estimated incidence of about 1 in 10,000 live births. To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec, and risdiplam. […] The aim of this narrative review was to provide an overview of the pre- and post-marketing evidence on the pharmacological treatments approved for the treatment of SMA by identifying preclinical and clinical studies registered in clinicaltrials.gov and in the EU PAS register from their inception until the 4 January 2023. […] To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, an antisense oligonucleotide, onasemnogene abeparvovec, a gene therapy, and risdiplam, a SMN2 pre-mRNA splicing small-drug modifier.

• #7 Therapy development for spinal muscular atrophy: perspectives for muscular dystrophies and neurodegenerative disorders | Neurological Research and Practice | Full Text

  https://neurolrespract.biomedcentral.com/articles/10.1186/s42466-021-00162-9

  Major efforts have been made in the last decade to develop and improve therapies for proximal spinal muscular atrophy (SMA). The introduction of Nusinersen/Spinraza as an antisense oligonucleotide therapy, Onasemnogene abeparvovec/Zolgensma as an AAV9-based gene therapy and Risdiplam/Evrysdi as a small molecule modifier of pre-mRNA splicing have set new standards for interference with neurodegeneration. […] Therapies for SMA are designed to interfere with the cellular basis of the disease by modifying pre-mRNA splicing and enhancing expression of the Survival Motor Neuron (SMN) protein, which is only expressed at low levels in this disorder. […] The development of therapies for SMA was based on the use of cell culture systems and mouse models, as well as innovative clinical trials that included readouts that had originally been introduced and optimized in preclinical studies.

• #8 Spinal Muscular Atrophy Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1181436-treatment

  Nusinersen (Spinraza) is the first drug approved to treat children (including newborns) and adults with SMA. Nusinersen is an antisense oligonucleotide (ASO) designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. […] Nusinersen approval was based on the ENDEAR trial. The ENDEAR trial (n=121) is a phase 3 randomized, double-blind, sham-controlled study in patients with infantile-onset (most likely to develop Type 1) SMA. […] Onasemnogene abeparvovec (Zolgensma) is a recombinant AAV9-based gene therapy designed to deliver a copy of the gene encoding the human survival motor neuron (SMN) protein. […] Approval was based on the ongoing phase 3 STR1VE trial and the completed phase 1 START trial. […] Risdiplam (Evrysdi) is a survival of motor neuron 2 (SMN2) mRNA splicing modifier designed to treat mutations in chromosome 5q that lead to SMN protein deficiency.

• #9 Spinal muscular atrophy (SMA) | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/spinal-muscular-atrophy-sma

  There is no cure for SMA, but there are some promising treatments being tested in clinical trials. […] There is currently no specific treatment for SMA. However, research for a treatment is moving forward at a fast pace. Support is available for children with SMA and their families so they can achieve maximum quality of life. […] In contrast, the care of a child or adult with SMA types 3 or 4 will focus on physiotherapy to help maintain muscle strength and mobility. A multidisciplinary team of healthcare professionals will be needed to manage the symptoms of SMA.

• #10 Spinal Muscular Atrophy Treatment | International Program in Texas | CHRISTUS Children’s

  https://www.christushealth.org/get-care/services-specialties/pediatric-care/neurology/spinal-muscular-atrophy-sma

  Spinal muscular atrophy, also known as SMA, is a genetic disorder that affects the part of the nervous system that controls our ability to move our muscles voluntarily. […] There are now treatments that target both of these genes (SMN1 and SMN2) to make more SMN protein to improve the health of the motor neurons in those with SMA. […] CHRISTUS Children’s is a leader in treating Spinal Muscular Atrophy, or SMA. We provide FDA-approved treatment and have treated children from Turkey, Ukraine and Denmark and other parts of the world. […] The Food and Drug Administration (FDA) has approved three treatment opportunities for patients with Spinal Muscular Atrophy. These treatments include Nusinersen (Spinraza), Risdiplam (Evrysdi), and onasemnogene abeparvovec-xioi(Zolgensma). […] Spinraza is given intrathecally (via a needle in the back directly into the spinal fluid) approximately every 4 months.

• #11 Gene Therapy for Spinal Muscular Atrophy (SMA) | Children’s Hospital of Philadelphia

  https://www.chop.edu/treatments/gene-therapy-spinal-muscular-atrophy-sma

  Spinal muscular atrophy is caused by mutations in a gene called survival motor neuron 1 (or SMN1). […] There have been recent advancements in treating SMA with gene therapy. Gene therapy for SMA is called onasemnogene abeparvovec-xioi (brand name Zolgensma). […] Zolgensma delivers a new, working copy of a human SMN gene that is administered in a one-time infusion to children under 2 years old. […] Childrens Hospital of Philadelphia currently offers the one and only FDA-approved gene therapy for SMA: onasemnogene abeparvovec-xioi (brand name Zolgensma). […] CHOP also offers nusinersen (brand name Spinraza) and risdiplam (brand name Evrysdia) for the treatment of SMA in children and adults. […] In May 2019, Zolgensma was approved by the FDA for treatment of children under age 2 years with all forms and types of SMA. […] While the approved therapies for SMA are limited at this time, there are many medications currently being studied with the hope they may also become treatment options.

• #12 FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease

  The U.S. Food and Drug Administration today approved Zolgensma (onasemnogene abeparvovec-xioi), the first gene therapy approved to treat children less than two years of age with spinal muscular atrophy (SMA), the most severe form of SMA and a leading genetic cause of infant mortality. […] Patients with SMA now have another treatment option to minimize the progression of SMA and improve survival. […] Zolgensma is indicated for the treatment of children less than two years of age with SMA. The product is an adeno-associated virus vector-based gene therapy that targets the cause of SMA. The vector delivers a fully functional copy of human SMN gene into the target motor neuron cells. A one-time intravenous administration of Zolgensma results in expression of the SMN protein in a child’s motor neurons, which improves muscle movement and function, and survival of a child with SMA.

• #13 Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges

  https://www.mdpi.com/2073-4425/15/8/999

  Spinal muscular atrophy (SMA) is a severe genetic disorder characterized by the loss of motor neurons, leading to progressive muscle weakness, loss of mobility, and respiratory complications. In its most severe forms, SMA can result in death within the first two years of life if untreated. The condition arises from mutations in the SMN1 (survival of motor neuron 1) gene, causing a deficiency in the survival motor neuron (SMN) protein. […] Recent therapeutic advancements include antisense oligonucleotides (ASOs), small molecules targeting SMN2, and virus-mediated gene replacement therapy delivering a functional copy of SMN1. Additionally, recognizing SMA’s broader phenotype involving multiple organs has led to the development of SMN-independent therapies. […] Several therapeutic strategies, such as nusinersen, onasemnogene abeparvovec, and risdiplam, have gained regulatory approval by the FDA and EMA for the treatment of SMA. These approaches aim to enhance SMN production either by modifying SMN2 splicing or by replacing the defective SMN1 gene.

• #14 Spinal Muscular Atrophy Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1181436-treatment

  The indication was expanded to include children younger than 2 months in May 2022. Approval was supported by results from several phase 3 trials (FIREFISH, SUNFISH, JEWELFISH, RAINBOWFISH). […] Medications such as valproic acid, phenylbutyrate, hydroxyurea, and albuterol have been shown to increase SMN transcription in laboratory studies, but clinical trials have not demonstrated significant improvement in disease progression. […] Supportive treatment should be aimed at improving the patients’ quality of life and minimizing disability, particularly in patients with slow progression. […] The treatment of patients with adult-onset spinal muscular atrophy is similar to that for amyotrophic lateral sclerosis (ALS), except that the course and life span in spinal muscular atrophies is considerably longer.

• #15 Importance of Spinal Muscular Atrophy (SMA) Treatment | Evrysdi® (risdiplam)

  https://www.evrysdi-hcp.com/about-evrysdi/importance-of-treatment.html

  Spinal muscular atrophy (SMA) may cause muscle atrophy over time […] Spinal muscular atrophy (SMA) may cause eating and swallowing difficulties over time […] Spinal muscular atrophy (SMA) may cause orthopedic complications over time […] Spinal muscular atrophy (SMA) may cause loss of motor functions over time […] Spinal muscular atrophy (SMA) may cause respiratory complications over time […] Despite several treatment options, many people with SMA face obstacles to receiving disease-modifying treatment. Barriers include: Prior lack of clinical study information in adults, Challenges administering medicine, Inability to travel, Financial considerations […] Disease-modifying treatments offer the opportunity to slow disease progression and maintain or improve motor function. […] Treatment goals include: Stabilizing the course of the disease in later-onset SMA, Reducing functional loss in adults and children, Enabling survival in infants.

• #16 Spinal Muscular Atrophy (SMA) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/spinal-muscular-atrophy

  On Dec. 23, 2016, the U.S. Food and Drug Administration (FDA) approved Spinraza (nusinersen) for the treatment of SMA. Spinraza is designed to treat the underlying defect in SMA, which means it potentially may be effective at slowing, stopping, or perhaps reversing the symptoms of SMA. […] In May 2019, the FDA approved Zolgensma (onasemnogene abeparvovac-xioi), the first gene-replacement therapy for a neuromuscular disease. Zolgensma is a one-time intravenous (into the vein) infusion for the treatment of pediatric patients younger than 2 years of age with SMA with bi-allelic mutations in the SMN1 gene, including those who are presymptomatic at diagnosis. […] In August 2020, the FDA approved risdiplam (brand name Evrysdi*) for the treatment of SMA in adults and children two months of age or older. Evysdi is an oral medication designed to increase levels of the SMN protein by enhancing production from the SMN2 „backup” gene. In May 2022, the FDA approved a label extension for Evrysdi to be used for babies under two months of age based on data from the RAINBOWFISH clinical trials (NCT03779334) of newborns that demonstrated that pre-symptomatic babies treated with Evrysdi within this age group achieved crucial motor milestones.

• #17 Spinal Muscular Atrophy Treatment – Cure SMA

  https://www.curesma.org/spinal-muscular-atrophy-treatment/

  There are several (SMA) spinal muscular atrophy treatments approved. Each individual or family must make treatment decisions based on your needs, goals, and values in consultation and discussion with your healthcare provider. […] One way of treating SMA is to increase the amount of survival motor neuron protein in the body. This is often called an SMN-based or SMN-enhancing approach. […] Many SMN-enhancing treatments target the SMN2 gene, causing it to make more useable SMN protein. Other SMN-enhancing approaches work to replace the function of or repair the mutated SMN1 gene. […] Increasing the amount of SMN protein in the body is not the only way to treat SMA. […] Many researchers believe that it will take a combination of SMN-based and non-SMN treatments to provide the most benefit for those with SMA.

• #18 Gene-based therapy for the treatment of spinal muscular atrophy types 1 and 2 : a systematic review and meta-analysis | Gene Therapy

  https://www.nature.com/articles/s41434-024-00503-8

  Nusinersen is an antisense oligonucleotide that binds to a specific sequence in intron 7 of SMN2 pre-mRNA to facilitate the inclusion of exon 7 in the final mRNA transcript, subsequently producing a functional SMN protein. […] Risdiplam is the first small molecule that works by increasing the inclusion of exon 7 of SMN2 transcripts, allowing the production of full-length SMN protein. […] Onasemnogene abeparvovec resulted in the highest number of patient survivals and motor function improvements and reduced the number of patients who needed ventilatory support. […] However, it showed approximately the same improvement in the CHOP-INTEND score as nusinersen.

• #19 How Gene Therapy Works | ZOLGENSMA® (onasemnogene abeparvovec-xioi)

  https://www.zolgensma.com/how-zolgensma-works

  ZOLGENSMA is an essential, one-time treatment option. […] ZOLGENSMA (onasemnogene abeparvovec-xioi) is the only treatment that addresses the genetic cause of spinal muscular atrophy (SMA) with just one dose, and is a type of medicine called gene therapy. ZOLGENSMA works by increasing the amount of SMN protein in the body to keep the muscles working as they should. […] ZOLGENSMA is a gene therapy for SMA that replaces the missing or nonworking SMN1 gene with a new, working SMN gene. The new SMN gene helps the body’s cells—particularly the motor neuron cells—to keep producing SMN protein. […] ZOLGENSMA is the only gene therapy for SMA that replaces the missing or nonworking SMN1 gene by delivering a new, working SMN gene to the body’s cells with a single infusion. ZOLGENSMA is engineered to keep continuously working in the body.

• #20 Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10605203/

  Onasemnogene abeparvovec was approved in 2020 as the first, and currently unique, gene therapy for SMA, and it was indicated for SMA patients aged 2 years with bi-allelic mutations in the SMN1 gene and three or fewer copies of the SMN2 gene or infantile-onset SMA. […] The replacement of the SMN1 defective gene is an alternative therapeutic approach that has been recently explored. […] The success of nusinersen considerably boosted research for further therapies, in particular for those administered through a less invasive route. […] The marketing approval of risdiplam was based on two pivotal clinical trials: the FIREFISH trial in infantile-onset SMA and the SUNFISH trial in late-onset SMA. […] Post-marketing studies, including both observational studies and clinical trials, play a crucial role in better understanding the clinical benefits and the safety of orphan drugs in real-world settings.

• #21 Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges

  https://www.mdpi.com/2073-4425/15/8/999

  Nusinersen (Spinraza) is an antisense oligonucleotide (ASO) that was the first treatment approved for SMA. The FDA granted approval in December 2016, followed by EMA approval in May 2017. Nusinersen works by promoting the inclusion of SMN2 exon 7 via ISS-N1 inhibition, thereby increasing the production of full-length SMN2 mRNA and subsequently full-length SMN protein. […] Onasemnogene Abeparvovec (ZOLGENSMA) is a gene therapy aimed at treating SMA by delivering a functional SMN1 gene to produce the vital SMN protein. […] Risdiplam (EVRYSDI) is the only approved oral medication for spinal muscular atrophy (SMA). It received FDA approval in August 2020 and EMA approval in March 2021 for patients two months and older with SMA types 1, 2, and 3, or with four copies of the SMN2 gene. […] The therapeutic landscape for spinal muscular atrophy (SMA) has seen remarkable advancements with significant progress in extending patient lives and improving motor function. Despite the success of FDA-approved treatments like nusinersen, onasemnogene abeparvovec, and risdiplam in improving patient outcomes, these therapies come with several challenges.

• #22

  https://link.springer.com/article/10.1007/s00431-023-04883-8

  The natural history of spinal muscular atrophy has been radically changed by the advent of improved standards of care and the availability of disease-modifying therapies. […] The aim of this paper is to provide the current therapeutic scenario including new perspectives and to report the challenges related to new phenotypes a few years after the therapies have become available. […] Clinical trials and real world data support the efficacy and safety profiles of the available drugs. At the moment there is not enough published evidence about the superiority of one product compared to the others. […] Safety and efficacy results of clinical trials have led in the last 6 years to the marketing of three drugs for spinal muscular atrophy, with different mechanisms of action. […] Since the drugs approval, real-world data allow us to have data on bigger and heterogeneous groups of patients in contrast with those included in clinical trials.

• #23 Medical Management – Spinal Muscular Atrophy (SMA) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/spinal-muscular-atrophy/medical-management

  Spinraza (nusinersen), a novel therapy that modifies the SMN2 gene in order to increase the production of normal and functional SMN2 protein, has been approved in several regions and countries, including the United States, Canada, Europe, Brazil, Australia, and Japan. Spinraza is administered by intrathecal injection (via an injection into the spinal canal, or into the subarachnoid space within the brain that’s connected to the spinal canal). Spinraza is recommended for most infants with SMA, especially those between 2 and 12 years old. […] Spinrazas approval by the US Food and Drug Administration (FDA) and the European Medicines Agency was based on the results of two large trials. One was named ENDEAR, which enrolled patients with SMA who were 7 months old or younger, and the other was named CHERISH, which enrolled patients 2 to 12 years old. These studies showed improvement in both lifespan and quality of life.

• #24 FDA approves innovative gene therapy to treat pediatric patients with spinal muscular atrophy, a rare disease and leading genetic cause of infant mortality | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal-muscular-atrophy-rare-disease

  The safety and effectiveness of Zolgensma is based on an ongoing clinical trial and a completed clinical trial involving a total of 36 pediatric patients with infantile-onset SMA between the ages of approximately 2 weeks and 8 months at study entry. […] Compared to the natural history of patients with infantile-onset SMA, patients treated with Zolgensma also demonstrated significant improvement in their ability to reach developmental motor milestones (e.g., head control and the ability to sit without support).

• #25 Gene-based therapy for the treatment of spinal muscular atrophy types 1 and 2 : a systematic review and meta-analysis | Gene Therapy

  https://www.nature.com/articles/s41434-024-00503-8

  Despite numerous studies identifying the advantages of therapies for spinal muscular atrophy (SMA), healthcare professionals encounter obstacles in determining the most effective treatment. […] This study aimed to investigate the effects of gene-based therapy for SMA. […] The outcomes measured were survival, the need for ventilatory support, improvements in motor function, and the occurrence of adverse drug reactions. […] A total of 57 studies (n=3418) were included, and the meta-analyses revealed that onasemnogene abeparvovec showed the highest survival rate (95% [95% CI: 88, 100]), followed by risdiplam (86% [95% CI: 76, 94]) and nusinersen (60% [95% CI: 50, 70]). […] The number of patients needing ventilatory support was reduced after treatment with onasemnogene abeparvovec (risk ratio=010 [95% CI: 002, 053]).

• #26 Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10605203/

  Onasemnogene abeparvovec was approved in 2020 as the first, and currently unique, gene therapy for SMA, and it was indicated for SMA patients aged 2 years with bi-allelic mutations in the SMN1 gene and three or fewer copies of the SMN2 gene or infantile-onset SMA. […] The replacement of the SMN1 defective gene is an alternative therapeutic approach that has been recently explored. […] The success of nusinersen considerably boosted research for further therapies, in particular for those administered through a less invasive route. […] The marketing approval of risdiplam was based on two pivotal clinical trials: the FIREFISH trial in infantile-onset SMA and the SUNFISH trial in late-onset SMA. […] Post-marketing studies, including both observational studies and clinical trials, play a crucial role in better understanding the clinical benefits and the safety of orphan drugs in real-world settings.

• #27 Should Treatment for Spinal Muscular Atrophy Be Initiated Earlier? – Neurology Advisor

  https://www.neurologyadvisor.com/features/treatment-spinal-muscular-atrophy-initiated-earlier-thomas-gillingwater-phd/

  Thomas Gillingwater, PhD, discusses how critical it is to start SMA treatment early in infants before the onset of symptoms. […] For conditions such as SMA, tools such as newborn screening, gene therapy, and other effective alternative treatments have shown potential in their ability to indelibly alter the outcomes and quality of life for pediatric patients, especially when treatments are provided prior to symptom onset. […] The idea of getting in early with therapy is to ameliorate as much of that presymptomatic developmental build-up that seems to set the system up to fail, said Dr Gillingwater. Restoring levels of SMN protein early reduces and minimizes the systemic developmental impact [leading] to the symptoms being much [less] when they do appear. […] Early presymptomatic treatment of SMA with gene therapy and nusinersen has improved patient outcomes, allowing many children to achieve major developmental milestones, such as walking independently, and to survive longer without the need for permanent ventilation or nutrition via mechanical support.

• #28 Highly Effective Gene Therapies for SMA: Where Do We Go From Here?

  https://www.neurologylive.com/view/highly-effective-gene-therapies-sma-where-do-we-go-from-here

  All treatments have shown profound benefits in infantile-onset SMA compared with the natural history of the disease. […] Current therapies can help to increase SMN protein levels, which may help to rescue sick motor neurons and prevent future loss of these critical cells. […] In study after study, including those looking at a presymptomatic dosing of nusinersen, risdiplam, and onasemnogene, findings have shown the largest benefits from early treatment, leading to the addition of SMA to the Department of Health and Human Services Recommended Uniform Screening Panel in 2018. […] Identification of SMA via NBS allows treatment to be started very early on in life, within the first 1 to 2 months. […] Current recommendations are to treat all individuals with 2 to 4 copies of SMN2. […] The potential to treat in utero is intriguing.

• #29 Spinal Muscular Atrophy: Four trials to watch over the next year

  https://www.clinicaltrialsarena.com/features/spinal-muscular-atrophy-trials-to-watch/

  With just five treatments available for spinal muscular atrophy, how are clinical trials trying to improve patients quality of life? […] In 2016, the first treatment for spinal muscular atrophy (SMA) was approved. Seven years on, there are just five marketed drugs for the indication according to GlobalDatas Pharmaceutical Intelligence Centre. […] Significant progress has been made over the past seven years but it remains difficult for patients to receive treatment for the disease due to inaccessibility. Are any trials looking to combat the unmet needs for patients, including lack of access to treatment? […] The Phase III SAPPHIRE trial (NCT05156320) is investigating the pipeline drug apitegromab in development by Scholar Rock. […] The trial will complete in June 2024. […] It is under development for the treatment of type 2 and type 3 SMA and is administered intravenously.

• #30 Advances and limitations for the treatment of spinal muscular atrophy | BMC Pediatrics | Full Text

  https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-022-03671-x

  Spinal muscular atrophy (5q-SMA; SMA), a genetic neuromuscular condition affecting spinal motor neurons, is caused by defects in both copies of the SMN1 gene that produces survival motor neuron (SMN) protein. […] Recently, three therapeutics that increase SMN protein levels in patients with SMA have provided incremental improvements in motor function and developmental milestones and prevented the worsening of SMA symptoms. […] While the therapeutic approaches with Spinraza, Zolgensma, and Evrysdi have a clinically significant impact, they are not curative. […] A potential combination therapy under development for SMA targets myostatin, a negative regulator of muscle mass and strength. […] A recently completed phase 2 trial demonstrated the potential clinical benefit of apitegromab by improving or stabilizing motor function in patients with Type 2 and Type 3 SMA and providing positive proof-of-concept for myostatin inhibition as a target for managing SMA.

• #31 6 Therapies on the Horizon for Spinal Muscular Atrophy – BioSpace

  https://www.biospace.com/drug-development/6-therapies-on-the-horizon-for-spinal-muscular-atrophy

  Last week, Novartis announced positive safety and efficacy readouts for OAV101 IT, an investigational intrathecal injection of its landmark gene therapy, Zolgensma (onasemnogene abeparvovec). […] Data from the Phase III STEER study, presented March 19 at the Muscular Dystrophy Association’s Clinical Scientific Conference in Dallas, showed that treatment with OAV101 IT improves motor muscular ability in patients 2-17 years of age, potentially expanding the cohort of patients who can benefit from this therapy. […] In STEER, OAV101 IT elicited a 2.39-point improvement on the Hammersmith Functional Motor Scale Expanded (HFMSE)—a gold standard SMA assessment tool, according to Novartis press release—compared to 0.51 points in the control arm. […] Scholar Rock’s apitegromab, a myostatin inhibitor, sailed through Phase III testing with flying colors.

• #32 Advances and limitations for the treatment of spinal muscular atrophy | BMC Pediatrics | Full Text

  https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-022-03671-x

  The primary goal of this manuscript is to orient physicians to the evolving landscape of SMA treatment. […] Treatment is more successful if patients are treated presymptomatically, suggesting newborn screening is highly beneficial for this patient population. […] The monoclonal antibody apitegromab which blocks the activation of the negative regulator of muscle growth, myostatin, is in clinical development. […] Apitegromab has provided evidence of the potential to treat SMA and may represent a unique, SMN-independent approach, specifically targeting both forms of promyostatin; more specifically, a muscle-targeted therapeutic option for patients that still experience motor function deficits despite SMN protein-increasing therapy. […] Apitegromab, in combination with an SMN upregulator may further enhance motor function. […] Myostatin inhibition in combination with SMN correctors may directly address muscle atrophy and further restore motor function.

• #33 6 Therapies on the Horizon for Spinal Muscular Atrophy – BioSpace

  https://www.biospace.com/drug-development/6-therapies-on-the-horizon-for-spinal-muscular-atrophy

  The higher-dose regimen, which comprises a loading regimen of two 50-mg doses 14 days apart, followed by a 28-mg maintenance regimen every four months, could enable meaningful clinical benefits while maintaining a safety profile broadly consistent with the approved 12-mg regimen. […] Biohaven’s investigational myostatin and activin receptor blocker, taldefgrobep alfa, missed the mark in a recent Phase III trial, but the Connecticut-based biotech hasn’t given up on the drug yet.

• #34 6 Therapies on the Horizon for Spinal Muscular Atrophy – BioSpace

  https://www.biospace.com/drug-development/6-therapies-on-the-horizon-for-spinal-muscular-atrophy

  Last week, Novartis announced positive safety and efficacy readouts for OAV101 IT, an investigational intrathecal injection of its landmark gene therapy, Zolgensma (onasemnogene abeparvovec). […] Data from the Phase III STEER study, presented March 19 at the Muscular Dystrophy Association’s Clinical Scientific Conference in Dallas, showed that treatment with OAV101 IT improves motor muscular ability in patients 2-17 years of age, potentially expanding the cohort of patients who can benefit from this therapy. […] In STEER, OAV101 IT elicited a 2.39-point improvement on the Hammersmith Functional Motor Scale Expanded (HFMSE)—a gold standard SMA assessment tool, according to Novartis press release—compared to 0.51 points in the control arm. […] Scholar Rock’s apitegromab, a myostatin inhibitor, sailed through Phase III testing with flying colors.

• #35 6 Therapies on the Horizon for Spinal Muscular Atrophy – BioSpace

  https://www.biospace.com/drug-development/6-therapies-on-the-horizon-for-spinal-muscular-atrophy

  In the Phase III SAPPHIRE trial, reported by Scholar Rock in October 2024, patients aged 2 to 12 years receiving apitegromab experienced clinically meaningful benefits in motor function, with the treatment group seeing at least a 1.8-point improvement on the HFMSE compared to placebo. […] Unlike other drugs, apitegromab directly targets muscles, selectively inhibiting the activation of myostatin. […] NMD Pharma is testing NMD670, a small molecule inhibitor of skeletal muscle-specific chloride ion channel 1 (CIC01), in a Phase II trial for SMA. […] In January, the FDA accepted Biogen’s supplemental new drug application for a higher dose of its Ionis-partnered Spinraza, an antisense oligonucleotide that alters the splicing of SMN2, a backup gene for SMN1 that produces a truncated version of the SMN protein.

• #36 Therapeutic strategy for spinal muscular atrophy by combining gene supplementation and genome editing | Nature Communications

  https://www.nature.com/articles/s41467-024-50095-5

  However, this gene supplementation therapy cannot assure permanent restoration of endogenous SMN1 expression due to the episomal nature of AAV vectors, preventing genomic integration into the host genomic DNA. […] The CRISPR-Cas9 technology is a powerful genome-editing system that holds promise for addressing common inherited diseases. […] The success of in situ gene correction of the SMN1 mutation holds the potential to provide a permanent cure for all SMA patients. […] Recently, we developed a non-homologous end joining (NHEJ)-based strategy for the targeted integration of transgenes, homology-independent targeted integration (HITI), effective in both dividing and non-dividing cells. […] Here, we introduce a novel approach, termed Gene-DUET, which combines gene cDNA supplementation with genome editing using HITI. Our study demonstrates significant advancements in long-term survival and amelioration of SMA phenotypes.

• #37 New Target Found for Treatment of Spinal Muscular Atrophy | Lurie Children’s

  https://www.luriechildrens.org/en/news-stories/new-target-found-for-treatment-of-spinal-muscular-atrophy/

  New approach could overcome the limitations of gene therapy for SMA. This discovery offers a new target for treatment that overcomes important limitations of gene therapy and other current therapies for SMA. Gene therapy has revolutionized SMA treatment, but it only works for a subgroup of patients and it can be too toxic. We are excited to offer promise of a brand new treatment for children with SMA, said senior author Dr. Ma. This means that inhibiting Cdk5 could treat all patients, including children whose SMA subtype makes them ineligible for gene therapy. This new approach also could potentially be used in combination with gene therapy. Once a better inhibitor is developed, treatment could start as soon as SMA is diagnosed through newborn screening, before symptoms appear. […] The researchers also demonstrated in mouse models and human induced pluripotent stem cell (iPSC) models of SMA that the mitochondrial dysfunction and motor neuron degeneration can be stopped by a Cdk5 inhibitor. After reducing Cdk5 activity, the mice showed significant improvement in SMA symptoms.

• #38 First-Ever Prenatal Treatment for Spinal Muscular Atrophy Shows Promise | MedPage Today

  https://www.medpagetoday.com/neurology/generalneurology/114283

  The first prenatal treatment for spinal muscular atrophy showed promise in a single case report. […] Risdiplam was given to the mother during pregnancy and to the child after birth. […] More than 2 years later, the child shows no features of the disease. […] The first prenatal therapy for spinal muscular atrophy (SMA) showed promising results, a case report indicated. […] The child was treated in utero with risdiplam (Evrysdi), which is approved to treat SMA in pediatric and adult patients, and continues to receive the oral drug daily. […] Risdiplam is an SMN2 pre-mRNA splicing modifier designed to increase and sustain SMN protein levels centrally and peripherally. […] It’s one of three drugs approved for SMA, the others being nusinersen (Spinraza) and onasemnogene abeparvovec (Zolgensma).

• #39 First-Ever Prenatal Treatment for Spinal Muscular Atrophy Shows Promise | MedPage Today

  https://www.medpagetoday.com/neurology/generalneurology/114283

  The overarching goal in this first case study was to demonstrate feasibility of prenatal therapy with one of these drugs, generate safety data, and gather biomarker and clinical data that might give a hint of improved efficacy when compared to initiation of treatment postnatally. […] Risdiplam was subsequently administered orally to the infant 8 days after birth and has been continued daily to the present time (at 30 months of age in February 2025). […] No features of SMA, including hypotonia, weakness, areflexia, or fasciculation, have emerged to date, Finkel and colleagues said. […] The case study may generate further discussion in the SMA community about whether prenatal treatment should be pursued further in formal clinical trials. […] It may offer another option for some babies that could optimize the response to treatment during a time of high motor neuron vulnerability.

• #40 Promising results from first prenatal therapy for spinal muscular atrophy – St. Jude Children’s Research Hospital

  https://www.stjude.org/media-resources/news-releases/2025-medicine-science-news/promising-results-from-first-prenatal-therapy-for-spinal-muscular-atrophy.html

  Prenatal therapy for spinal muscular atrophy (SMA) with risdiplam shows promise in a first-of-its-kind study published in The New England Journal of Medicine led by Richard Finkel, MD, St. Jude Center for Experimental Neurotherapeutics director and Department of Pediatric Medicine member. […] Scientists at St. Jude Childrens Research Hospital led the first in utero treatment of SMA with the orally administered drug risdiplam. More than two years after the child was born, no identifiable features of SMA have been observed. This study demonstrates the feasibility of treating SMA prenatally and supports further investigation into the approach. […] The results suggest it would be worthwhile to continue investigating the use of prenatal intervention for SMA. […] Currently, treatments for SMA-1 have demonstrated improved survival and motor function in infants, especially if administered shortly after birth before symptoms begin, but is not a cure. […] The research demonstrates the safety and feasibility of the approach and bolsters the case for a more comprehensive study.

• #41 Highly Effective Gene Therapies for SMA: Where Do We Go From Here?

  https://www.neurologylive.com/view/highly-effective-gene-therapies-sma-where-do-we-go-from-here

  One very active area of debate within the SMA community is the potential benefit (or lack thereof) of combination treatment. […] The data from these trials will augment early real-world experience with combination therapy. […] More recent trials have focused on alternative medications and treatments that may work in tandem with SMN replacement therapies, as well as in isolation, to further improve muscle strength.

• #42 Advances and limitations for the treatment of spinal muscular atrophy | BMC Pediatrics | Full Text

  https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-022-03671-x

  The primary goal of this manuscript is to orient physicians to the evolving landscape of SMA treatment. […] Treatment is more successful if patients are treated presymptomatically, suggesting newborn screening is highly beneficial for this patient population. […] The monoclonal antibody apitegromab which blocks the activation of the negative regulator of muscle growth, myostatin, is in clinical development. […] Apitegromab has provided evidence of the potential to treat SMA and may represent a unique, SMN-independent approach, specifically targeting both forms of promyostatin; more specifically, a muscle-targeted therapeutic option for patients that still experience motor function deficits despite SMN protein-increasing therapy. […] Apitegromab, in combination with an SMN upregulator may further enhance motor function. […] Myostatin inhibition in combination with SMN correctors may directly address muscle atrophy and further restore motor function.

• #43 Spinal Muscular Atrophy: Four trials to watch over the next year

  https://www.clinicaltrialsarena.com/features/spinal-muscular-atrophy-trials-to-watch/

  Dr Rose Joachim, director of Neurology at GlobalData, says that the different MOA that apitegromab offers in the SAPPHIRE trial could assist type 2 and 3 patients with very limited treatment options. […] Dr Sharon Hesterlee, executive vice president and chief research officer of the Muscular Dystrophy Association, believes apitegromab will work well with an SMN2 regulator due to the treatments having different targets. […] Novartis is nearing the end of its Phase III STEER trial of onasemnogene abeparvovec, marketed under the name Zolgensma. […] If proven efficacious, this trial will allow the treatment to be used in type 2 patients. […] Joachim says that onasemngene abeparvovec appears to offer something close to functional cure but the real question is the longevity. […] The DEVOTE study (NCT04089566) by Biogen is investigating the clinical efficacy of Spinraza (nusinersen) administered intrathecally at higher doses to subjects with SMA.

• #44

  https://link.springer.com/article/10.1007/s00431-023-04883-8

  In addition to the new molecules, combinations of therapies are currently being evaluated. […] The three therapies that so far have been approved are all targeting an increase of the protein survival motor neuron protein (SMN) that is deficient in SMA. […] This approach aims at addressing the root problem of the disease by replacing the mutated SMN1 gene. […] Onasemnogene abeparvovec was first investigated in an open-label, dose-escalation phase I clinical trial performed in 15 infants with early-onset SMA. […] Safety and efficacy data were confirmed by two large open-label, multicenter phase III studies in the USA and Europe in infants with early onset with an age below 7 months. […] The number of studies reporting real-world data using onasemnogene abeparvovec is still limited.

• #45 Spinal Muscular Atrophy Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1181436-treatment

  A multidisciplinary approach is essential. […] Interventions such as chest physiotherapy, assisted cough, nocturnal (+/- daytime) noninvasive ventilation, and Nissen fundoplication for nonsitting patients may be considered. […] The use of splints, bracing, and spinal orthoses can be customized to each patient. […] Patients and families can also be directed to ongoing clinical trials for the treatment of spinal muscular atrophies.

• #46 Spinal Muscular Atrophy | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/spinal-muscular-atrophy

  People with SMA can benefit from physical therapy, occupational therapy, and rehabilitation to help improve posture, prevent joint immobility, and slow muscle weakness and atrophy. […] It is important the people with SMA get proper nutrition to help them maintain weight and promote muscle function.

• #47 Guide | Physical Therapy Guide to Spinal Muscular Atrophy | Choose PT

  https://www.choosept.com/guide/physical-therapy-guide-spinal-muscular-atrophy

  Physical therapists help children and adults with SMA develop muscle strength. […] Physical therapy treatment helps people with SMA reach the highest level of independence and mobility possible. […] Early treatment with medicines and physical therapy at or shortly after diagnosis may greatly change the course of the disease and improve outcomes. […] Physical therapists work closely with children and adults with SMA and their families to develop treatment programs for their specific needs. […] Evidence supports the value of structured exercise programs for people with SMA to reduce disability and maintain mobility. […] Physical therapy treatment for people with SMA may include activities to maintain and improve overall movement and function. […] Physical therapists help you learn specific flexibility and range-of-motion exercises and positioning.

• #48 Spinal Muscular Atrophy: Causes, Symptoms, and Treatment

  https://www.webmd.com/brain/spinal-muscular-atrophy

  Besides gene therapy, your doctor may suggest a few other ways to help manage symptoms: […] Physical and occupational therapy, which use exercises and regular daily activities, can help protect your child’s joints and keep muscles strong. A therapist may suggest leg braces, a walker, or an electric wheelchair. Special tools can control computers and phones and help with writing and drawing.

• #49 Guide | Physical Therapy Guide to Spinal Muscular Atrophy | Choose PT

  https://www.choosept.com/guide/physical-therapy-guide-spinal-muscular-atrophy

  Physical therapists work with people to help keep the spine and body supported and aligned during daily activities. […] Respiratory exercise training is essential for people with SMA to prevent breathing problems. […] Physical therapists work with other specialists to select and modify suitable devices to meet each person’s specific needs. […] Exercise may help to improve aerobic fitness in people with SMA. […] Physical therapists help people who cannot stand on their own get any equipment needed to start a daily standing program for home or school. […] Physical therapists work closely with speech and occupational therapists to promote healthy feeding. […] Another treatment option is aquatic therapy or hydrotherapy. […] Physical therapists also will evaluate you or your child again shortly after surgery. […] Early movement after surgery is often recommended, so developing a plan of action before surgery is important. […] Recently, several medicines have advanced treatment and improved the lives of people with SMA.

• #50 Spinal Muscular Atrophy Treatment and Therapy Options | mySMAteam

  https://www.mysmateam.com/resources/treatments-for-spinal-muscular-atrophy-sma

  Common side effects of risdiplam include diarrhea, vomiting, and rash. […] Ventilation assistance helps people with SMA who have breathing problems live longer, healthier lives. […] Many doctors suggest starting with noninvasive ventilation support. […] If noninvasive ventilation isn’t working well, your doctor may recommend invasive ventilation. […] Some people with SMA have scoliosis (an abnormal curve in the spine). […] Weak respiratory muscles make it difficult for people with SMA to cough and clear mucus from their lungs. […] A speechlanguage pathologist (SLP) can help a person with SMA overcome problems with speech and swallowing. […] Physical therapy (PT) can help people with SMA move better and become stronger. […] Occupational therapy focuses on increasing independence in daily activities at home, at work, or in school.

• #51 Spinal Muscular Atrophy Treatment and Therapy Options | mySMAteam

  https://www.mysmateam.com/resources/treatments-for-spinal-muscular-atrophy-sma

  Common side effects of risdiplam include diarrhea, vomiting, and rash. […] Ventilation assistance helps people with SMA who have breathing problems live longer, healthier lives. […] Many doctors suggest starting with noninvasive ventilation support. […] If noninvasive ventilation isn’t working well, your doctor may recommend invasive ventilation. […] Some people with SMA have scoliosis (an abnormal curve in the spine). […] Weak respiratory muscles make it difficult for people with SMA to cough and clear mucus from their lungs. […] A speechlanguage pathologist (SLP) can help a person with SMA overcome problems with speech and swallowing. […] Physical therapy (PT) can help people with SMA move better and become stronger. […] Occupational therapy focuses on increasing independence in daily activities at home, at work, or in school.

• #52 Spinal Muscular Atrophy Treatment and Therapy Options | mySMAteam

  https://www.mysmateam.com/resources/treatments-for-spinal-muscular-atrophy-sma

  Nearly all children with SMA develop scoliosis, which can be treated in many ways. […] People with SMA may benefit from other forms of treatment, including certain diets, exercise, immunizations, and complementary and alternative treatments. […] It’s crucial for babies and small children with SMA to get enough nutrients and calories for brain growth and development. […] Most doctors recommend exercising to your comfort level and tolerance. […] People with SMA are at an especially high risk of respiratory infections. […] It’s highly unlikely that any natural or alternative treatment will effectively treat SMA.

• #53 SMA (Spinal Muscular Atrophy): What It Is, Symptoms & Types

  https://my.clevelandclinic.org/health/diseases/14505-spinal-muscular-atrophy-sma

  Spinal muscular atrophy (SMA) is a genetic condition that causes worsening muscle weakness. […] Theres no cure for SMA, but certain therapies and medications can help manage symptoms. […] Treatment for SMA mainly seeks to manage symptoms and prevent complications. Symptom management therapies may include: Physical therapy, which can help improve posture, prevent joint immobility and slow muscle weakness. Occupational therapy, which can improve your ability to perform daily tasks. Assistive devices, like orthopaedic braces, crutches, walkers and wheelchairs. Therapy for speech and swallowing difficulties. A feeding tube if swallowing is too difficult and/or dangerous. Assisted ventilation for breathing issues. […] Between 2016 and 2020, the U.S. Food and Drug Administration (FDA) approved treatments that can significantly improve the course of SMA. They include: Disease-modifying therapy: These medications stimulate the production of SMN2 protein. The FDA has approved Nusinersen (Spinraza) for both children and adults. A healthcare provider injects the medication into the space around your spinal canal. A different medication, risdiplam (Evrysdi), helps those with SMA who are 2 months and older. You take risdiplam daily by mouth (orally). Gene replacement therapy: Children younger than 2 may benefit from a one-time intravenous (IV) infusion of a medication called onasemnogene abeparvovec-xioi (Zolgensma). This therapy replaces a missing or faulty SMN1 gene with a functioning gene. […] These newer treatments may be particularly effective if started early, even before symptoms of SMA appear. Given the availability of these treatments, theres now routine screening of newborns for SMA in the United States.

• #54 Should Treatment for Spinal Muscular Atrophy Be Initiated Earlier? – Neurology Advisor

  https://www.neurologyadvisor.com/features/treatment-spinal-muscular-atrophy-initiated-earlier-thomas-gillingwater-phd/

  Thomas Gillingwater, PhD, discusses how critical it is to start SMA treatment early in infants before the onset of symptoms. […] For conditions such as SMA, tools such as newborn screening, gene therapy, and other effective alternative treatments have shown potential in their ability to indelibly alter the outcomes and quality of life for pediatric patients, especially when treatments are provided prior to symptom onset. […] The idea of getting in early with therapy is to ameliorate as much of that presymptomatic developmental build-up that seems to set the system up to fail, said Dr Gillingwater. Restoring levels of SMN protein early reduces and minimizes the systemic developmental impact [leading] to the symptoms being much [less] when they do appear. […] Early presymptomatic treatment of SMA with gene therapy and nusinersen has improved patient outcomes, allowing many children to achieve major developmental milestones, such as walking independently, and to survive longer without the need for permanent ventilation or nutrition via mechanical support.

• #55 Highly Effective Gene Therapies for SMA: Where Do We Go From Here?

  https://www.neurologylive.com/view/highly-effective-gene-therapies-sma-where-do-we-go-from-here

  All treatments have shown profound benefits in infantile-onset SMA compared with the natural history of the disease. […] Current therapies can help to increase SMN protein levels, which may help to rescue sick motor neurons and prevent future loss of these critical cells. […] In study after study, including those looking at a presymptomatic dosing of nusinersen, risdiplam, and onasemnogene, findings have shown the largest benefits from early treatment, leading to the addition of SMA to the Department of Health and Human Services Recommended Uniform Screening Panel in 2018. […] Identification of SMA via NBS allows treatment to be started very early on in life, within the first 1 to 2 months. […] Current recommendations are to treat all individuals with 2 to 4 copies of SMN2. […] The potential to treat in utero is intriguing.

• #56 Highly Effective Gene Therapies for SMA: Where Do We Go From Here?

  https://www.neurologylive.com/view/highly-effective-gene-therapies-sma-where-do-we-go-from-here

  All treatments have shown profound benefits in infantile-onset SMA compared with the natural history of the disease. […] Current therapies can help to increase SMN protein levels, which may help to rescue sick motor neurons and prevent future loss of these critical cells. […] In study after study, including those looking at a presymptomatic dosing of nusinersen, risdiplam, and onasemnogene, findings have shown the largest benefits from early treatment, leading to the addition of SMA to the Department of Health and Human Services Recommended Uniform Screening Panel in 2018. […] Identification of SMA via NBS allows treatment to be started very early on in life, within the first 1 to 2 months. […] Current recommendations are to treat all individuals with 2 to 4 copies of SMN2. […] The potential to treat in utero is intriguing.

• #57 Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10605203/

  As of the 4 January 2023, a total of 69 studies concerning the three orphan drugs approved for SMA were identified in clinicaltrials.gov (N = 65; 94.2%) and in the EU PAS register (N = 4; 5.8%). […] The ongoing studies were mainly aimed at providing further evidence concerning the effectiveness of the three drugs on disease progression in specific populations that had not been included in the pivotal trials (e.g., adults, older adults, and pregnant women) and at investigating the long-term safety and clinical benefits of these drugs. […] Overall, the evidence on the pharmacological therapies for SMA is still limited and should be cautiously interpreted. […] Despite the considerable advances in scientific research concerning the pharmacological treatments of SMA, some issues related to each of the three approved drugs remain, and caution is needed when interpreting study results, especially for adult patients.

• #58 Spinal Muscular Atrophy Type 4: Symptoms, Treatment, and Outlook

  https://www.healthline.com/health/spinal-muscular-atrophy/spinal-muscular-atrophy-type-4

  Nusinersen, sold in the United States as Spinraza, is the first Food and Drug Administration (FDA)-approved medication for treating SMA. This medication targets the backup SMN2 gene to help your body produce full-length SMN protein. […] Research suggests that nusinersen may improve the progression of SMA, but it remains expensive. The first year of treatment costs about $708,000. […] Theres currently no data on the effectiveness of nusinersen for SMA type 4, but experts think its most effective to start treatment soon after diagnosis. […] Another medication called risdiplam (Evrysdi) is also FDA-approved to treat the condition in adults and children over the age of 2 months. […] Other treatment options for SMA type 4 aim to reduce symptoms and improve quality of life. They include: physical therapy and occupational therapy, walking aids, such as a cane or a walker, splints or braces for your arms and legs, orthotics to help with walking, surgery. […] The medication nusinersen may help improve its progression, although research looking specifically at its effect on SMA type 4 is lacking. […] Researchers are also continuing to examine new potential treatments for SMA.

• #59 Importance of Spinal Muscular Atrophy (SMA) Treatment | Evrysdi® (risdiplam)

  https://www.evrysdi-hcp.com/about-evrysdi/importance-of-treatment.html

  Spinal muscular atrophy (SMA) may cause muscle atrophy over time […] Spinal muscular atrophy (SMA) may cause eating and swallowing difficulties over time […] Spinal muscular atrophy (SMA) may cause orthopedic complications over time […] Spinal muscular atrophy (SMA) may cause loss of motor functions over time […] Spinal muscular atrophy (SMA) may cause respiratory complications over time […] Despite several treatment options, many people with SMA face obstacles to receiving disease-modifying treatment. Barriers include: Prior lack of clinical study information in adults, Challenges administering medicine, Inability to travel, Financial considerations […] Disease-modifying treatments offer the opportunity to slow disease progression and maintain or improve motor function. […] Treatment goals include: Stabilizing the course of the disease in later-onset SMA, Reducing functional loss in adults and children, Enabling survival in infants.

• #60 How Gene Therapy Works | ZOLGENSMA® (onasemnogene abeparvovec-xioi)

  https://www.zolgensma.com/how-zolgensma-works

  By replacing the SMN1 gene, ZOLGENSMA enables the production of SMN protein and helps preserve essential muscle function. […] ZOLGENSMA is the only gene therapy that replaces the SMN1 gene to stop the progression of SMA. […] ZOLGENSMA is a prescription gene therapy used to treat children less than 2 years old with spinal muscular atrophy (SMA). ZOLGENSMA is given as a one-time infusion into a vein.

• #61 MED.00129 Gene Therapy for Spinal Muscular Atrophy

  https://www.anthem.com/dam/medpolicies/abcbs/active/policies/mp_pw_d092916.html

  The product was approved for single intravenous administration only; repeat administration of Zolgensma and its use in individuals with advanced SMA (e.g. need for permanent ventilatory support or complete limb paralysis) have not been evaluated. […] Trials have excluded individuals with AAAV9 antibody titers 1:50, serious concomitant illness, and dependence on ventilatory support (tracheotomy with positive pressure or use of non-invasive ventilator support [BiPAP] for more than 16 hours per day [Phase I]). […] A Phase III open-label single-arm trial known as STRIVE, conducted in the United States, was published in 2021 by Day and colleagues. […] The trial evaluated the dosage used in the commercial onasemnogene abeparvovec-xioi product, which was the higher dose used in the Phase 1 trial.

• #62 MED.00129 Gene Therapy for Spinal Muscular Atrophy

  https://www.anthem.com/dam/medpolicies/abcbs/active/policies/mp_pw_d092916.html

  A total of 22 individuals were enrolled in the STRIVE trial at a mean age of 3.7 months (standard deviation [SD], 1.6 months). […] At 18 months of age, 13 of 22 (59%) individuals achieved the co-primary endpoint of independent sitting for at least 30 seconds. […] The primary efficacy outcome was the ability to sit for at least 30 seconds through 18 months of age in the 2-copy cohort and the ability to stand independently for at least 3 seconds at up to 24 months of age in the 3-copy cohort. […] The primary efficacy endpoint was independent standing for at least 3 seconds at any visit up to 24 months of age in the 3-copy cohort. […] Individuals with SMA type 1 are predicted to have two copies of the SMN2 gene. […] The first medication specifically developed for SMA, nusinersen (Spinraza) was approved by the FDA in 2016.

• #63 Advances and limitations for the treatment of spinal muscular atrophy | BMC Pediatrics | Full Text

  https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-022-03671-x

  The primary goal of this manuscript is to orient physicians to the evolving landscape of SMA treatment. […] Treatment is more successful if patients are treated presymptomatically, suggesting newborn screening is highly beneficial for this patient population. […] The monoclonal antibody apitegromab which blocks the activation of the negative regulator of muscle growth, myostatin, is in clinical development. […] Apitegromab has provided evidence of the potential to treat SMA and may represent a unique, SMN-independent approach, specifically targeting both forms of promyostatin; more specifically, a muscle-targeted therapeutic option for patients that still experience motor function deficits despite SMN protein-increasing therapy. […] Apitegromab, in combination with an SMN upregulator may further enhance motor function. […] Myostatin inhibition in combination with SMN correctors may directly address muscle atrophy and further restore motor function.

• #64

  https://www.curesma.org/

  Three approved treatments for SMA […] FDA Grants Priority Review for Biologics License Application (BLA) for Apitegromab as a Treatment for Spinal Muscular Atrophy.

• #65 Spinal Muscular Atrophy Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1181436-treatment

  A multidisciplinary approach is essential. […] Interventions such as chest physiotherapy, assisted cough, nocturnal (+/- daytime) noninvasive ventilation, and Nissen fundoplication for nonsitting patients may be considered. […] The use of splints, bracing, and spinal orthoses can be customized to each patient. […] Patients and families can also be directed to ongoing clinical trials for the treatment of spinal muscular atrophies.

• #66 Spinal Muscular Atrophy (SMA) Program | Boston Children’s Hospital

  https://www.childrenshospital.org/programs/spinal-muscular-atrophy-program

  Children with spinal muscular atrophy (SMA) need care from experts in several medical fields. The Spinal Muscular Atrophy Program at Boston Childrens Hospital brings together a team of specialists who are experienced in caring for children with this rare and complex condition. […] In recent years, several new treatments have been FDA-approved for SMA, including gene replacement treatment and two drugs. As a leader in caring for children with SMA, we have been a part of the clinical trials for all of these treatment options and have extensive experience prescribing them for our patients. […] We hold a dedicated SMA clinic once or twice a month. The clinic allows you to meet with all of your childs SMA-related providers during a single visit. It also gives us the opportunity to evaluate your childs health as a whole and to work with your family to make the best treatment decisions. […] Our clinic also gives you the chance to meet other families affected by SMA and to learn about research opportunities. […] The Spinal Muscular Atrophy Program at Boston Childrens has been supported by the Spinal Muscular Atrophy Foundation and Cure SMA since 2004.

• #67 Spinal Muscular Atrophy (SMA) Program | Boston Children’s Hospital

  https://www.childrenshospital.org/programs/spinal-muscular-atrophy-program

  Children with spinal muscular atrophy (SMA) need care from experts in several medical fields. The Spinal Muscular Atrophy Program at Boston Childrens Hospital brings together a team of specialists who are experienced in caring for children with this rare and complex condition. […] In recent years, several new treatments have been FDA-approved for SMA, including gene replacement treatment and two drugs. As a leader in caring for children with SMA, we have been a part of the clinical trials for all of these treatment options and have extensive experience prescribing them for our patients. […] We hold a dedicated SMA clinic once or twice a month. The clinic allows you to meet with all of your childs SMA-related providers during a single visit. It also gives us the opportunity to evaluate your childs health as a whole and to work with your family to make the best treatment decisions. […] Our clinic also gives you the chance to meet other families affected by SMA and to learn about research opportunities. […] The Spinal Muscular Atrophy Program at Boston Childrens has been supported by the Spinal Muscular Atrophy Foundation and Cure SMA since 2004.

• #68 Spinal muscular atrophy (SMA) – NHS

  https://www.nhs.uk/conditions/spinal-muscular-atrophy-sma/

  There is currently no cure for spinal muscular atrophy (SMA), but there are treatments and support available to help people with SMA have the best possible quality of life. […] The main treatment for SMA is medicines that target the altered genes that cause SMA, including: nusinersen (Spinraza), risdiplam (Evrysdi), onasemnogene abeparvovec (Zolgensma). […] It’s not always possible to have medicines to help treat SMA. The most suitable treatments will depend on your or your child’s age and symptoms. Your care team will be able to discuss the risks and benefits of any possible treatments. […] Treatment and support is also available for the symptoms of SMA. Every person’s needs will be different depending on their symptoms. […] Support you or your child might need may include: physiotherapy, exercises and stretches to help maintain strength and stop joints becoming stiff, mobility equipment (including walking frames and wheelchairs), supports for the arms or legs (splints or braces) or shoe inserts that make walking easier (orthotics), help with breathing problems, such as breathing exercises or machines that help clear mucus from the airways or provide air through a mask, help with swallowing problems, such as making diet changes or using a feeding tube that’s passed down the nose or attached directly through the tummy, a back brace or surgery to help with spine problems. […] People with SMA are also usually advised to have the flu vaccine and pneumococcal vaccine.

• #69 Spinal Muscular Atrophy Treatment and Therapy Options | mySMAteam

  https://www.mysmateam.com/resources/treatments-for-spinal-muscular-atrophy-sma

  Nearly all children with SMA develop scoliosis, which can be treated in many ways. […] People with SMA may benefit from other forms of treatment, including certain diets, exercise, immunizations, and complementary and alternative treatments. […] It’s crucial for babies and small children with SMA to get enough nutrients and calories for brain growth and development. […] Most doctors recommend exercising to your comfort level and tolerance. […] People with SMA are at an especially high risk of respiratory infections. […] It’s highly unlikely that any natural or alternative treatment will effectively treat SMA.

• #70 Spinal Muscular Atrophy Treatment and Therapy Options | mySMAteam

  https://www.mysmateam.com/resources/treatments-for-spinal-muscular-atrophy-sma

  Nearly all children with SMA develop scoliosis, which can be treated in many ways. […] People with SMA may benefit from other forms of treatment, including certain diets, exercise, immunizations, and complementary and alternative treatments. […] It’s crucial for babies and small children with SMA to get enough nutrients and calories for brain growth and development. […] Most doctors recommend exercising to your comfort level and tolerance. […] People with SMA are at an especially high risk of respiratory infections. […] It’s highly unlikely that any natural or alternative treatment will effectively treat SMA.

• #71 Spinal Muscular Atrophy | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/spinal-muscular-atrophy

  People with SMA can benefit from physical therapy, occupational therapy, and rehabilitation to help improve posture, prevent joint immobility, and slow muscle weakness and atrophy. […] It is important the people with SMA get proper nutrition to help them maintain weight and promote muscle function.

• #72 Spinal Muscular Atrophy (SMA) | St. Jude Care & Treatment

  https://www.stjude.org/care-treatment/treatment/neurological-disorders/spinal-muscular-atrophy.html

  To learn more about SMA and current treatments, visit organizations dedicated to SMA and rare diseases. […] Select children with SMA who are accepted at St. Jude take part in clinical research or clinical trials. The aim of these studies is to help scientists learn more about the disorders and to develop potential treatments. […] To study how different SMA drugs affect muscles and nerve cells and to study the use of MRI to track muscle changes. […] To learn more about participants beliefs, attitudes, and questions about gene therapy to help make web-based resources to share information. This could help patients make treatment decisions. […] We are thankful that St. Jude is venturing into neuromuscular disorders, and we are happy to be part of a study that can not only help our daughter but also help others with similar disorders.

• #73 Spinal Muscular Atrophy (SMA) – Seattle Children’s

  https://www.seattlechildrens.org/conditions/spinal-muscular-atrophy/

  Spinraza helps your childs body produce more, better-quality SMN protein. […] Evrysdi is the first oral (by mouth) drug treatment for SMA. […] Seattle Childrens Neuromuscular Program offers the most comprehensive care in the Pacific Northwest for children with SMA. […] Our full range of treatments includes gene therapy and other medicines, physical therapy and equipment, respiratory support and orthopedic surgery. […] Seattle Childrens was the first hospital in Washington state to offer a gene replacement therapy called onasemnogene abeparvovec-xioi (Zolgensma) for SMA. […] Our active clinical trials program means your child may have the chance to receive promising new therapies in a research study that matches their specific situation.

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