Add-On Therapy for SMA-Dr. Klotz Presentation

Dr. Klotz Presentation

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The document provides an overview of updates on antisense oligonucleotides (ASOs) in treating Spinal Muscular Atrophy (SMA), focusing on add-on therapy and high-dose regimens using nusinersen. Antisense oligonucleotides are precise molecules that bind to target pre-mRNA to modify splicing and increase the production of functional proteins. Despite challenges like poor uptake and crossing the blood-brain barrier, they are administered intrathecally to address these issues.<br /><br />The document highlights key clinical trials and studies, such as ENDEAR, CHERISH, EMBRACE, and NURTURE, which indicate significant improvements in motor function and safety of nusinersen treatment. Real-world data supports these findings, revealing clinically meaningful motor improvements in both children and adults with SMA. Despite some adverse effects related to lumbar punctures, nusinersen-related side effects remain low.<br /><br />In terms of therapy after gene replacement therapy (GRT) with nusinersen, the RESPOND study suggests that nusinersen can be safely administered, although the clinical improvement must be carefully differentiated from ongoing GRT effects. Additionally, higher doses of nusinersen appear safe and show promising efficacy, as demonstrated in the DEVOTE study, which reported no new safety events and improved efficacy indicators compared to standard dosing.<br /><br />New advancements include the potential development of novel ASOs such as BIIB115, which might allow for less frequent dosing with increased potency. Ongoing research spans other administration methods, like a subcutaneous intrathecal catheter system being evaluated in PIERRE studies, to reduce sedation needs over long-term treatment.<br /><br />The document underlines the need for continuous assessment and feedback on these therapies' development and application, pushing for innovations in the management of SMA.

Keywords

antisense oligonucleotides

Spinal Muscular Atrophy

SMA

nusinersen

clinical trials

motor function improvement

gene replacement therapy

high-dose regimens

BIIB115

subcutaneous intrathecal catheter

therapy advancements

spinal muscular atrophy

SMA