Ignite Creation Date:
2024-05-06 @ 5:14 PM
Last Modification Date:
2024-10-26 @ 2:24 PM
Study NCT ID:
NCT05237544
Status:
COMPLETED
Last Update Posted:
2022-02-14
First Post:
2019-06-12
Brief Title:
Newborn Screening for Spinal Muscular Atrophy SMA - a Proof of Principle Study Using Anonymised Blood Spots
Sponsor:
Great Ormond Street Hospital for Children NHS Foundation Trust
Organization:
Great Ormond Street Hospital for Children NHS Foundation Trust
Study Overview
Official Title:
Newborn Screening for Spinal Muscular Atrophy SMA - a Proof of Principle Study Using Anonymised Blood Spots
Status:
COMPLETED
Status Verified Date:
2022-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Spinal muscular atrophy SMA is a motor neuron disorder caused by the absence of a functional survival of motor neuron 1 telomeric SMN1 gene Type I SMA a lethal disease of infancy accounts for the majority of cases Newborn blood spot screening NBSto detect SMA has been implemented in public health laboratories in some countries already In the UK dried blood spots are collected within a few days of birth on all babies and subsequent newborn screening is currently carried out for other diseases but not for SMA The investigators would like to carry out a proof of principal testing to show that an assay for SMA can be carried out on these routinely collected dried blood spots completely anonymised The investigators would also run some known anonymised SMA positive dried blood spots The aim is to demonstrate that a simple robust test can be used in a routine diagnostic laboratory to accurately screen for SMA The investigators will not have access to identifiable data or samples for this project
Detailed Description:
Spinal muscular atrophy SMA is a motor neuron disorder caused by the absence of a functional survival of motor neuron 1 telomeric SMN1 gene Type I SMA a lethal disease of infancy accounts for the majority of cases The majority of babies born with SMA become symptomatic as babies type I or as toddlers type II Type I children will never sit unsupported require ventilated support in the first year of life and usually die before 2 years of age Type II children can survive to early adulthood but will never walk They almost invariably develop severe curvature of the spine feeding and respiratory insufficiency that require appropriate intervention Cognitive abilities are not impaired and children are generally bright and sociable
Several new therapies have recently been developed for children with SMA and have shown remarkable success in clinical trials One of these therapies spinraza has received both FDA and EMA approval and is commercially available in most EU countries and in the US and is being currently evaluated by NICE Because of the early onset and rapid progression of infantile SMA prompt detection of the disease is essential to enable successful treatment It is now recommended that infants be screened for SMA enabling early drug treatment thus preventing further neuron damage2 The recently published work on the development of spinraza indeed supports the view that children with shorter disease duration had much better outcome the 2 NEJM papers a concept that is also emphasised by the interim analysis of infants who received spinraza presymptomatically as part of an ongoing study sponsored by Biogen Nurture study The majority of these children had met the age appropriate milestones by the age of 1 year a clearly remarkable outcome Similar very promising results were obtained in a recently published AAV gene therapy study in which a number of the severe infants affected by type 1 SMA achieved even the ability to walk unsupported Mendell SMA gene therapy NEJM 2017 Also in this manuscript the children who had a shorter disease duration and those treated shortly after the diagnosis had a much better outcome compared to children treated later While the findings from this early gene therapy study are currently being extended in a larger global phase 3 study these dramatic results from emerging therapies have led many countries to include SMA in their respective newborn screening programmes
A previous study Adams et al 2014 J Clin Imm was carried out in an almost identical way to the study planned here The previous study utilised 5000 anonymised leftover blood spots from a routine NBS lab to test the robustness and practicality of running a NBS assay for SCID This study was scientifically critiqued leading to publication in a respected relevant scientific journal The study planned here is identical in the approach 5000 normal leftover blood spots to test the robustness and practicality of using a commercial assay for NBS for SMA in a routine clinical lab environment As in the previous SCID study we plan to use a number of retrospective known positive samples as well as all the necessary positivenegative controls contained in the commercial kit The sole aim of the study is to assess the performance of the commercial kit to provide evidence that NBS screening for SMA could feasibly be carried out in routine NBS screening labs
The investigators therefore believe this is the correct route to take with SMA Newborn Screening as well Assays for detection of SMA using the dried blood spots collected for Newborn Screening NBS have now been developed This utilises the amplification of the SMN1 gene and subsequent detection of the deleted section that causes SMA Newborn blood spot screening to detect SMA has been implemented in public health laboratories in some countries already In the UK dried blood spots are collected within a few days of birth on all babies and subsequent newborn screening is currently carried out for other diseases but not for SMA
The investigators would like to carry out a proof of principal testing to show that an assay for SMA can be carried out on these anonymised routinely collected dried blood spots We would also run some known anonymised SMA positive dried blood spots The aim is to demonstrate that a simple robust test can be used in a routine diagnostic laboratory to accurately screen for SMA
Several new therapies have recently been developed for children with SMA and have shown remarkable success in clinical trials One of these therapies spinraza has received both FDA and EMA approval and is commercially available in most EU countries and in the US and is being currently evaluated by NICE Because of the early onset and rapid progression of infantile SMA prompt detection of the disease is essential to enable successful treatment It is now recommended that infants be screened for SMA enabling early drug treatment thus preventing further neuron damage2 The recently published work on the development of spinraza indeed supports the view that children with shorter disease duration had much better outcome the 2 NEJM papers a concept that is also emphasised by the interim analysis of infants who received spinraza presymptomatically as part of an ongoing study sponsored by Biogen Nurture study The majority of these children had met the age appropriate milestones by the age of 1 year a clearly remarkable outcome Similar very promising results were obtained in a recently published AAV gene therapy study in which a number of the severe infants affected by type 1 SMA achieved even the ability to walk unsupported Mendell SMA gene therapy NEJM 2017 Also in this manuscript the children who had a shorter disease duration and those treated shortly after the diagnosis had a much better outcome compared to children treated later While the findings from this early gene therapy study are currently being extended in a larger global phase 3 study these dramatic results from emerging therapies have led many countries to include SMA in their respective newborn screening programmes
A previous study Adams et al 2014 J Clin Imm was carried out in an almost identical way to the study planned here The previous study utilised 5000 anonymised leftover blood spots from a routine NBS lab to test the robustness and practicality of running a NBS assay for SCID This study was scientifically critiqued leading to publication in a respected relevant scientific journal The study planned here is identical in the approach 5000 normal leftover blood spots to test the robustness and practicality of using a commercial assay for NBS for SMA in a routine clinical lab environment As in the previous SCID study we plan to use a number of retrospective known positive samples as well as all the necessary positivenegative controls contained in the commercial kit The sole aim of the study is to assess the performance of the commercial kit to provide evidence that NBS screening for SMA could feasibly be carried out in routine NBS screening labs
The investigators therefore believe this is the correct route to take with SMA Newborn Screening as well Assays for detection of SMA using the dried blood spots collected for Newborn Screening NBS have now been developed This utilises the amplification of the SMN1 gene and subsequent detection of the deleted section that causes SMA Newborn blood spot screening to detect SMA has been implemented in public health laboratories in some countries already In the UK dried blood spots are collected within a few days of birth on all babies and subsequent newborn screening is currently carried out for other diseases but not for SMA
The investigators would like to carry out a proof of principal testing to show that an assay for SMA can be carried out on these anonymised routinely collected dried blood spots We would also run some known anonymised SMA positive dried blood spots The aim is to demonstrate that a simple robust test can be used in a routine diagnostic laboratory to accurately screen for SMA
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None