Pathophysiological Insights Derived by Natural History and Motor Function of Spinal Muscular Atrophy

Farrar, Michelle A.; Vucic, Steve; Johnston, Heather; Sart, Desirée du; Kiernan, Matthew C.

doi:10.1016/j.jpeds.2012.05.067

Cited by 112 publications

(104 citation statements)

References 28 publications

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“…12 The onset of symptoms for SMA type 2 occurs between 6 and 18 months of age; children are not able to walk independently; survival past 2 years of age is common; historically, children rarely survived into adulthood, although this has changed in recent years with management. 12,13 SMA type 3 is the mildest form of childhood SMA with age of onset greater than 18 months, and is further sub-classified into types 3a and 3b, when presentation is before or after 3 years of age, respectively; children are able to walk, but many later lose ambulation, and they have problems with gross and fine motor skills; they achieve a reasonably normal lifespan. 13 Advances in respiratory care have improved survival rates in individuals with SMA types 2 and 3.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 SMA type 3 is the mildest form of childhood SMA with age of onset greater than 18 months, and is further sub-classified into types 3a and 3b, when presentation is before or after 3 years of age, respectively; children are able to walk, but many later lose ambulation, and they have problems with gross and fine motor skills; they achieve a reasonably normal lifespan. 13 Advances in respiratory care have improved survival rates in individuals with SMA types 2 and 3. 13 Recently, Farrar et al 13 described the detailed natural history and survival probabilities of 70 patients presenting to a specialised clinic in Australia between 1995 and 2010.…”

Section: Introductionmentioning

confidence: 99%

“…13 Advances in respiratory care have improved survival rates in individuals with SMA types 2 and 3. 13 Recently, Farrar et al 13 described the detailed natural history and survival probabilities of 70 patients presenting to a specialised clinic in Australia between 1995 and 2010. These patients had undergone genetic testing following initial clinical diagnostic investigations after parental or health professional concern about development, primarily symptoms such as hypotonia, weakness and motor delay.…”

Section: Introductionmentioning

confidence: 99%

“…Although these authors briefly mentioned parental reports of the early clinical symptoms, no studies have described parental experiences of leading up to and receiving a diagnosis, which could indicate a potential diagnostic odyssey, and the impact on families. 13 This study aimed to explore the experiences of family members regarding the journey to receiving a diagnosis, and their views on the potential for earlier diagnosis through screening.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy

et al. 2014

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy

et al. 2014

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“…Starsze publikacje oraz prace z ośrodków, w którym prowadzono jedynie leczenie paliatywne, wskazują na medianę przeżycia około 6-7 miesięcy dla SMA1 [11,12]. Według badań australijskich szansa przeżycia 1, 2, 4 i 10 lat dla dzieci z SMA1 wynosi odpowiednio 40%, 25%, 6% i 0% [13]. Polsko-niemieckie badania z 2002 roku wskazywały z kolei, że około 10% pacjentów z SMA1 dożywa 5. roku życia [14].…”

Section: Historia Naturalnaunclassified

Spinal muscular atrophy – novel therapies, new challenges

Jędrzejowska¹,

Kostera‐Pruszczyk²

2017

Child Neurology

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STRESZCZENIERdzeniowy zanik mięśni jest postępującą chorobą neurodegeneracyjną, w przebiegu której dochodzi do utraty motoneuronów rdzenia kręgowego, a w konsekwencji osłabienia i zaniku mięśni. Choroba charakteryzuje się bardzo dużą zmiennością przebiegu klinicznego -od letalnej formy wrodzonej po postać dorosłą, o średniej przeżycia jak w populacji ogólnej. Choroba związana jest z mutacjami genu SMN1. Liczba kopii bliźniaczo podobnego genu SMN2 warunkuje nasilenie objawów klinicznych. Analizy ostatnich lat zaowocowały weryfikacją aktualnej klasyfikacji, poprawą standardów opieki, poznaniem przebiegu historii naturalnej choroby. W zderzeniu z nowymi badaniami nad podłożem molekularnym i patogenezą choroby możliwe stało się podjęcie prób terapeutycznych. Badania kliniczne wykazały skuteczność nusinersenu (anysensowny oligonukleotyd), i doprowadziły do rejestracji leku do leczenia SMA. Najlepsze efekty uzyskano u pacjentów, u których włączono leczenie w okresie przedobjawowym. Trwają badania nad kolejnymi substancjami, których działanie oparte jest o różnorodne strategie-począwszy od terapii genowej (AVXS101), przez mikromolekuły modyfikujące składanie pre-mRNA SMN2 (LMI070, RG7916), po neuroprotektory (Olesoxime) i wiele innych. W pracy dokonujemy przeglądu najnowszych danych dotyczą-cych klasyfikacji, historii naturalnej, standardów opieki i prób terapeutycznych. Wczesne rozpoznanie i leczenie może zmienić historię naturalną choroby. Dlatego tak ważne wydaje się wczesne rozpoznanie, a w przyszłości być może wprowadzenie skriningu noworodkowego. Słowa kluczowe: SMA 5q, białko SMN, terapia. ABSTRACTSpinal muscle atrophy (SMA) is a progressive neurodegenerative disease that results in the loss of motoneurons in the spinal cord and, consequently, in muscle weakness and atrophy. The disease is characterized by high variability of the clinical course -from the early neonatal form to the adult form, with the average survival as in the general population. The disease is caused by mutations in the SMN1 gene. The number of copies of a similar SMN2 gene determines the severity of clinical symptoms. Recent analyzes allowed to verify current classification, improve care standards, learn the natural history of SMA. Clinical studies showed the efficacy of nusinersen (an antysense oligonucleotide) and led to the registration of the drug for SMA treatment. The best results were seen in presymptomatic patients. Research is underway on substances that are based on a variety of strategies, from gene therapy (AVXS101) to SMN2 pre-mRNA modulation micronucleus (LMI070, RG7916) to neuroprotectants (Olesoxime) and many others. We review the latest data on classification, natural history, care standards and therapeutic trials. Early diagnosis and treatment can change the natural history of the disease. That is why it is so important to have an early diagnosis and, perhaps, a neonatal screening in the future.

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Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy

Schwartz,

Vill,

Pfaffenlehner

et al. 2024

JAMA Pediatr

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ImportanceThere is increasing evidence that early diagnosis and treatment are key for outcomes in infants with spinal muscular atrophy (SMA), and newborn screening programs have been implemented to detect the disease before onset of symptoms. However, data from controlled studies that reliably confirm the benefits of newborn screening are lacking.ObjectiveTo compare data obtained on patients with SMA diagnosed through newborn screening and those diagnosed after clinical symptom onset.Design, Setting, and ParticipantsThis nonrandomized controlled trial used data from the SMARTCARE registry to evaluate all children born between January 2018 and September 2021 with genetically confirmed SMA and up to 3 SMN2 copies. The registry includes data from 70 participating centers in Germany, Austria, and Switzerland. Data analysis was performed in February 2023 so that all patients had a minimal follow-up of 18 months.ExposurePatients born in 2 federal states in Germany underwent screening in a newborn screening pilot project. All other patients were diagnosed after clinical symptom onset. All patients received standard care within the same health care system.Main OutcomesThe primary end point was the achievement of motor milestones.ResultsA total of 234 children (123 [52.6%] female) were identified who met inclusion criteria and were included in the analysis: 44 (18.8%) in the newborn screening cohort and 190 children (81.2%) in the clinical symptom onset cohort. The mean (SD) age at start of treatment with 1 of the approved disease-modifying drugs was 1.3 (2.2) months in the newborn screening cohort and 10.7 (9.1) months in the clinical symptom onset cohort. In the newborn screening cohort, 40 of 44 children (90.9%) gained the ability to sit independently vs 141 of 190 (74.2%) in the clinical symptom onset cohort. For independent ambulation, the ratio was 28 of 40 (63.6%) vs 28 of 190 (14.7%).Conclusions and RelevanceThis nonrandomized controlled trial demonstrated effectiveness of newborn screening for infants with SMA in the real-world setting. Functional outcomes and thus the response to treatment were significantly better in the newborn screening cohort compared to the unscreened clinical symptom onset group.Trial RegistrationGerman Clinical Trials Register: DRKS00012699

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Pathophysiological Insights Derived by Natural History and Motor Function of Spinal Muscular Atrophy

Cited by 112 publications

References 28 publications

A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy

A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy

Spinal muscular atrophy – novel therapies, new challenges

Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy

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