https://www.ajmc.com/view/researchers-outline-promising-future-for-sma-dmd-with-emergence-of-gene-therapies-asos
Researchers Outline Promising Future for SMA, DMD With Emergence of Gene Therapies, ASOs
September 12, 2020
www.SMATreatmentReport.com
https://www.ajmc.com/view/researchers-outline-promising-future-for-sma-dmd-with-emergence-of-gene-therapies-asos
Researchers Outline Promising Future for SMA, DMD With Emergence of Gene Therapies, ASOs
September 12, 2020
https://clinicaltrials.gov/ct2/show/NCT03837184?type=Intr&cond=spinal+muscular+atrophy&phase=0124&lupd_s=08%2F27%2F2020&lupd_d=14&sort=nwst
STUDY TITLE:
Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies
DESCRIPTION:
Condition: Spinal Muscular Atrophy Type I
Intervention: Biological: Onasemnogene Abeparvovec-xioi
Sponsors: AveXis, Inc.; PRA Health Sciences
Active, not recruiting
CLINICALTRIALS.GOV IDENTIFIER:
NCT03837184
FIRST POSTED:
Tue, 12 Feb 2019 12:00:00 EST
LAST UPDATE POSTED:
09/10/20 07:19AM
STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT03837184?type=Intr&cond=spinal+muscular+atrophy&phase=0124&lupd_s=08%2F27%2F2020&lupd_d=14&sort=nwst
https://onlinelibrary.wiley.com/doi/abs/10.1002/ppul.25055
https://doi.org/10.1002/ppul.25055
https://pubmed.ncbi.nlm.nih.gov/32886442/
TITLE:
Overview of Gene Therapy in Spinal Muscular Atrophy and Duchenne Muscular Dystrophy
ALTERNATIVE TITLE:
None
DATE:
Verify – Fri, 04 Sep 2020 06:00:00 -0400
AUTHORS:
Nicolas J Abreu,Megan A Waldrop
SOURCE:
Pediatric pulmonology
DESCRIPTION:
Both 5q-linked spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are fatal monogenic neuromuscular disorders caused by loss-of-function mutations. SMA is an autosomal recessive disorder affecting motor neurons that is typically caused by homozygous whole-gene deletions of SMN1. DMD is an X-linked recessive muscle disease most often due to exon deletions, but also duplications and smaller sized variants within the DMD gene. Gene replacement therapy offers the opportunity to…
CONTENT:
Pediatr Pulmonol. 2020 Sep 4. doi: 10.1002/ppul.25055. Online ahead of print.
ABSTRACT
Both 5q-linked spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are fatal monogenic neuromuscular disorders caused by loss-of-function mutations. SMA is an autosomal recessive disorder affecting motor neurons that is typically caused by homozygous whole-gene deletions of SMN1. DMD is an X-linked recessive muscle disease most often due to exon deletions, but also duplications and smaller sized variants within the DMD gene. Gene replacement therapy offers the opportunity to correct the underlying genetic defect by the introduction of a functional gene. We review the transformative work from clinical trials to United States Food and Drug Administration approval of onasemnogene abeparvovec-xioi in SMA and its application in clinical practice and the early results of microdystrophin delivery in DMD. We also review the introduction of antisense oligonucleotides to alter pre-mRNA splicing to promote exon inclusion (as in nusinersen in SMA) or exclusion (as in eteplirsen in DMD) into neuromuscular therapeutics. There are multiple promising novel genetically mediated therapies on the horizon, which in aggregate point towards a hopeful future for individuals with SMA and DMD. This article is protected by copyright. All rights reserved.
PMID:32886442 | DOI:10.1002/ppul.25055
PUBMED ID:
pubmed:32886442
OTHER ID:
pmid:32886442,doi:10.1002/ppul.25055
PUBLICATION DATE:
Fri, 04 Sep 2020 06:00:00 -0400
2020-09-05
RETRIEVAL DATE :
09/04/20 06:43PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/32886442/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1l7lJQBQXfTBJkL86rnvYKzafMiKbgcUrlv_X8_D_H5EuRmkjR&fc=20200708141943&ff=20200904184345&v=2.11.5
LINK – DOI:
https://doi.org/10.1002/ppul.25055
LINK – FULL TEXT:
Pending
NOTES:
None
https://www.ejpn-journal.com/article/S1090-3798(20)30166-5/fulltext
https://doi.org/10.1016/j.ejpn.2020.08.005
https://pubmed.ncbi.nlm.nih.gov/32873505/
TITLE:
Gene therapy for spinal muscular atrophy: Solomon’s consensus in Covid times
ALTERNATIVE TITLE:
None
DATE:
Verify – Wed, 02 Sep 2020 06:00:00 -0400
AUTHORS:
Dimitrios Zafeiriou
SOURCE:
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
DESCRIPTION:
No abstract
CONTENT:
Eur J Paediatr Neurol. 2020 Aug 21:S1090-3798(20)30166-5. doi: 10.1016/j.ejpn.2020.08.005. Online ahead of print.
NO ABSTRACT
PMID:32873505 | DOI:10.1016/j.ejpn.2020.08.005
PUBMED ID:
pubmed:32873505
OTHER ID:
pmid:32873505,doi:10.1016/j.ejpn.2020.08.005
PUBLICATION DATE:
Wed, 02 Sep 2020 06:00:00 -0400
2020-09-03
RETRIEVAL DATE :
09/02/20 06:13AM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/32873505/?utm_source=Other&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1l7lJQBQXfTBJkL86rnvYKzafMiKbgcUrlv_X8_D_H5EuRmkjR&fc=20200708141943&ff=20200902061349&v=2.11.5
LINK – DOI:
https://doi.org/10.1016/j.ejpn.2020.08.005
LINK – FULL TEXT:
Pending
NOTES:
None
https://clinicaltrials.gov/ct2/show/NCT04042025?type=Intr&cond=Spinal+Muscular+Atrophy&lupd_s=06%2F24%2F2020&lupd_d=14&sort=nwst
STUDY TITLE:
Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi
DESCRIPTION:
Conditions: Spinal Muscular Atrophy Type I; Spinal Muscular Atrophy Type II; Spinal Muscular Atrophy Type III
Intervention: Biological: Onasemnogene Abeparvovec-xioi
Sponsor: AveXis, Inc.
Enrolling by invitation
CLINICALTRIALS.GOV IDENTIFIER:
NCT04042025
FIRST POSTED:
Thu, 01 Aug 2019 12:00:00 EDT
LAST UPDATE POSTED:
07/08/20 07:39AM
STUDY LINK / URL:
https://clinicaltrials.gov/ct2/show/NCT04042025?type=Intr&cond=Spinal+Muscular+Atrophy&lupd_s=06%2F24%2F2020&lupd_d=14&sort=nwst
https://www.prweb.com/releases/catalent_gene_therapy_facility_receives_fda_approval_as_an_additional_manufacturing_site_for_avexis_gene_therapy/prweb17307018.htm
Catalent Gene Therapy Facility Receives FDA Approval as an Additional Manufacturing Site for AveXis’ Gene Therapy
Share Article
Catalent, the leading global provider of advanced delivery technologies, development, and manufacturing solutions for drugs, biologics, cell and gene therapies, and consumer health products, today announced that it was approved by the U.S. Food and Drug Administration (FDA) to produce commercial drug substance intermediate for AveXis’ spinal muscular atrophy (SMA) gene therapy at its manufacturing facility located in Harmans, Maryland.
https://onlinelibrary.wiley.com/doi/abs/10.1002/mus.27034
https://doi.org/10.1002/mus.27034
https://pubmed.ncbi.nlm.nih.gov/32710634/
TITLE:
Combination molecular therapies for type 1 spinal muscular atrophy
ALTERNATIVE TITLE:
None
DATE:
Verify – Sat, 25 Jul 2020 06:00:00 -0400
AUTHORS:
Yohei Harada,Vamshi K Rao,Kapil Arya,Nancy L Kuntz,Christine J DiDonato,Galia Napchan-Pomerantz,Amit Agarwal,Vikki Stefans,Masahisa Katsuno,Aravindhan Veerapandiyan
SOURCE:
Muscle & nerve
DESCRIPTION:
INTRODUCTION: Data on combining molecular therapies that increase survival motor neuron protein for spinal muscular atrophy type 1 (SMA1) is lacking.
CONTENT:
Muscle Nerve. 2020 Jul 25. doi: 10.1002/mus.27034. Online ahead of print.
ABSTRACT
INTRODUCTION: Data on combining molecular therapies that increase survival motor neuron protein for spinal muscular atrophy type 1 (SMA1) is lacking.
METHODS: This was a retrospective study describing our centers’ experiences in treating SMA1 patients with combination therapy.
RESULTS: Five children received nusinersen and onasemnogene abeparvovec-xioi (onasemnogene). Four were receiving nusinersen prior to onasemnogene. Nusinersen was continued in three. Marked liver enzyme elevations resulted in prolonged corticosteroid treatment in two patients with hospitalization and liver biopsy in one; milder liver enzyme elevations were noted in the other two. One patient received onasemnogene first, and then nusinersen. No adverse effects were noted. All patients improved.
DISCUSSION: Combination molecular therapy is tolerated in SMA1 patients. Further studies are needed to determine whether there are circumstances in which combination therapy would be more efficacious than either monotherapy. Prolonged corticosteroid use and liver toxicity monitoring may be necessary with onasemnogene therapy. This article is protected by copyright. All rights reserved.
PMID:32710634 | DOI:10.1002/mus.27034
PUBMED ID:
pubmed:32710634
OTHER ID:
pmid:32710634,doi:10.1002/mus.27034
PUBLICATION DATE:
Sat, 25 Jul 2020 06:00:00 -0400
2020-07-26
RETRIEVAL DATE :
07/25/20 06:28PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/32710634/?utm_source=MS-Office&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1l7lJQBQXfTBJkL86rnvYKzafMiKbgcUrlv_X8_D_H5EuRmkjR&fc=20200708141943&ff=20200725182855&v=2.11.3
LINK – DOI:
https://doi.org/10.1002/mus.27034
LINK – FULL TEXT:
Pending
NOTES:
None
https://onlinelibrary.wiley.com/doi/abs/10.1002/med.21705
https://doi.org/10.1002/med.21705
https://pubmed.ncbi.nlm.nih.gov/32638429/
TITLE:
Modern approaches in gene therapy of motor neuron diseases
ALTERNATIVE TITLE:
None
DATE:
Verify – Wed, 08 Jul 2020 06:00:00 -0400
AUTHORS:
Maria Zakharova
SOURCE:
Medicinal research reviews
DESCRIPTION:
Motor neuron disorders are a group of neurodegenerative diseases characterized by muscle weakness, loss of ambulation, respiratory insufficiency, leading to an early death. Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis are the most common and fatal motor neuron diseases. The last 3 years became very successful for novel gene therapy approaches in SMA in infants. Two innovative drugs-nusinersen (Spinraza) and onasemnogene abeparvovec (Zolgensma) have been approved by health…
CONTENT:
Zakharova M. Med Res Rev 2020 – Review .
ABSTRACT
Motor neuron disorders are a group of neurodegenerative diseases characterized by muscle weakness, loss of ambulation, respiratory insufficiency, leading to an early death. Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis are the most common and fatal motor neuron diseases. The last 3 years became very successful for novel gene therapy approaches in SMA in infants. Two innovative drugs-nusinersen (Spinraza) and onasemnogene abeparvovec (Zolgensma) have been approved by health authorities. The numerous molecular and genetic overlaps between different neurodegenerative diseases are of great importance in the development of innovative therapeutic strategies, including viral vector therapy and RNA modulating approaches.
PMID:32638429 | DOI:10.1002/med.21705
PUBMED ID:
pubmed:32638429
OTHER ID:
pmid:32638429,doi:10.1002/med.21705
PUBLICATION DATE:
Wed, 08 Jul 2020 06:00:00 -0400
2020-07-09
RETRIEVAL DATE :
07/08/20 02:24PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/32638429/?utm_source=MS-Office&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1l7lJQBQXfTBJkL86rnvYKzafMiKbgcUrlv_X8_D_H5EuRmkjR&fc=20200708141943&ff=20200708142144&v=2.10.1
LINK – DOI:
https://doi.org/10.1002/med.21705
LINK – FULL TEXT:
Pending
NOTES:
None
https://www.sciencedirect.com/science/article/abs/pii/S089865682030173X?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/32553550?dopt=Abstract
TITLE:
Characteristics of circular RNAs generated by human Survival Motor Neuron genes.
DESCRIPTION:
Characteristics of circular RNAs generated by human Survival Motor Neuron genes.
Cell Signal. 2020 Jun 15;:109696
Authors: Ottesen EW, Singh RN
Abstract
Circular RNAs (circRNAs) belong to a diverse class of stable RNAs expressed in all cell types. Their proposed functions include sponging of microRNAs (miRNAs), sequestration and trafficking of proteins, assembly of multimeric complexes, production of peptides, and regulation of transcription. Backsplicing due to RNA structures formed by an exceptionally high number of Alu repeats lead to the production of a vast repertoire of circRNAs by human Survival Motor Neuron genes, SMN1 and SMN2, that code for SMN, an essential multifunctional protein. Low levels of SMN due to deletion or mutation of SMN1 result in spinal muscular atrophy (SMA), a major genetic disease of infants and children. Mild SMA is also recorded in adult population, expanding the spectrum of the disease. Here we review SMN circRNAs with respect to their biogenesis, sequence features, and potential functions. We also discuss how SMN circRNAs could be exploited for diagnostic and therapeutic purposes.
PMID: 32553550 [PubMed – as supplied by publisher]
PMID:
PubMed:32553550
DATE FOUND:
06/20/20 06:00AM
LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32553550?dopt=Abstract
https://clinicaltrials.gov/ct2/show/NCT03837184
Single-Dose Gene Replacement Therapy Using for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies
Study Type : Interventional (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 3, Open-Label, Single-Arm, Single-Dose Gene Replacement Therapy Clinical Trial for Patients With Spinal Muscular Atrophy Type 1 With One or Two SMN2 Copies Delivering AVXS-101 by Intravenous Infusion
Actual Study Start Date : May 15, 2019
Estimated Primary Completion Date : April 1, 2021
Estimated Study Completion Date : April 1, 2021
https://www.ncbi.nlm.nih.gov/pubmed/32129750
[Gene-based therapies of spinal muscular atrophy: a piece of history of medicine].https://journals.viamedica.pl/neurologia_neurochirurgia_polska/article/view/64309
Spinal muscular atrophy — new therapies, new challenges
Vol 54, No 1 (2020)
Invited review article
Published online: 2020-01-10
Submitted: 2019-05-09
Accepted: 2019-10-19
RG7916 and LMI070 or SMN1 gene replacement therapy (AAV9-SMN).