DRUGapprovedaso
nusinersen
Brand names: Spinraza
Mechanism
Antisense oligonucleotide targeting SMN2 pre-mRNA ISS-N1 to promote exon 7 inclusion.
Approved indications
type1type2type3presymptomatic
Related claims (50)
| Type | Predicate | Conf | Source |
|---|---|---|---|
| drug efficacy | Nusinersen is approved for the treatment of spinal muscular atrophy (clinical trial result) | 100% | 34621235 |
| drug efficacy | Nusinersen is a medication that treats Spinal Muscular Atrophy. | 100% | 39690144 |
| safety | Cardiac arrest, autism spectrum disorder, and epilepsy emerged as potential new side effects of Nusinersen not previously listed. | 90% | 39690144 |
| drug efficacy | Delay in nusinersen infusions may have a relevant impact on the course of spinal muscular atrophy pathology (observed in patient cohort) | 80% | 34621235 |
| drug efficacy | Nusinersen treatment was associated with a significant improvement in EK2 (OR = 0.81, p = 0.001) (observed in patient cohort). | 69% | 35872571 |
| drug efficacy | Nusinersen treatment is associated with improvement in patient condition after one year in 84% of patients (observed in patient cohort). | 65% | 40451126 |
| motor function | High baseline motor function is associated with the probability of acquiring a sitting position in patients with SMA1 treated with nusinersen (clinical trial result). | 65% | 31799720 |
| splicing event | Nusinersen is an antisense oligonucleotide (ASO) targeting the splicing inhibitory sequence in the intron downstream of exon 7 from SMN2, thus increasing exon 7 inclusion. | 65% | 36408582 |
| biomarker | NPTX2 emerges as a potential biomarker of treatment response to nusinersen in pwSMA suggesting its significant pathophysiological role in late-onset SMA (observed in patient cohort). | 65% | W4411855648 |
| drug efficacy | Approximately 70% of infants appear to have a clinically significant response to nusinersen with improved motor function (clinical trial result). | 65% | 30414815 |
| drug efficacy | Nusinersen treatment is associated with a statistically significant (p = 0.042) improvement of HFMSE (clinical trial result). | 65% | 35832502 |
| drug efficacy | A total of 70% of patients in the pediatric cohort and 72% of patients in the adult cohort achieved a clinically meaningful improvement in motor function following nusinersen treatment (clinical trial result). | 65% | 38921951 |
| splicing event | Analysis of autopsy tissue from patients exposed to nusinersen showed increased SMN2 mRNA exon 7 inclusion in the spinal cord. | 65% | 27939059 |
| biomarker | NPTX2 emerges as a potential biomarker of treatment response to nusinersen in pwSMA suggesting its significant pathophysiological role in late-onset SMA. | 65% | 40868076 |
| splicing event | Nusinersen acts through prevention of skipping of exon 7 of *Survival Motor Neuron 2* (*SMN2*) by sequestering Intronic Splicing Silencer N1 (ISS-N1), located within *SMN2* intron 7. | 65% | 41551726 |
| splicing event | Nusinersen alters SMN2 pre-RNA splicing so exon 7 is included (clinical trial result). | 65% | 31093018 |
| drug efficacy | Nusinersen treatment was associated with a significant improvement in HFMSE (odds ratio [OR] 1.15, p = 0.006) (observed in patient cohort). | 65% | 35872571 |
| biomarker | Neurofilament heavy chain, tau protein, S100B protein, and neuron-specific enolase do not serve as potential biomarkers during the loading phase of nusinersen (observed in patient cohort). | 65% | 31671515 |
| splicing event | Nusinersen promotes the inclusion of exon 7 in SMN2 transcripts (observed in mouse model). | 65% | 32612161 |
| drug efficacy | Nusinersen treatment improved motor scores as measured by the Hammersmith Infant Neurological Examination-2 by 2.6% (p = .008) over the 22-month study period (clinical trial result). | 65% | 33608138 |
| biomarker | Muscle quantitative MRI (qMRI) may be a biomarker of disease progression in adult SMA3 patients during nusinersen treatment. | 65% | 35832502 |
| motor function | Intrathecal nusinersen treatment improves or stabilizes motor function in 90% of young children with spinal muscular atrophy types 1c-3a (clinical trial result). | 65% | 36382221 |
| neuroprotection | Increased MCP1/CCL2 levels indicate a possible neuroprotective mechanism associated with nusinersen therapy (observed in patient cohort). | 65% | 36525882 |
| gene expression | An increase in SMN expression by either SMN gene therapy replacement or the antisense oligonucleotide (ASO), Nusinersen, significantly upregulated the endogenous levels of GEMIN5 in mammalian cells and mutant GEMIN5-derived iPSC neurons. | 65% | 37369805 |
| drug efficacy | Nusinersen treatment was associated with a significant improvement in the 6-min walk test (OR = 1.07, p < 0.001) (observed in patient cohort). | 65% | 35872571 |
| gene expression | In tissues isolated from nusinersen-treated SMA patients, antisense oligonucleotide (ASO) concentration and full-length (exon 7 including) SMN2 (SMN2-FL) mRNA level increases were highest in lumbar and thoracic spinal cord. | 65% | 31589162 |
| motor function | Treatment with Nusinersen in SMA3 improves motor function in longstanding disease even in clinically advanced stages. | 65% | 33682724 |
| gene expression | HA2-ApoE(131-150), when conjugated to Nusinersen, significantly increased the level of full-length functional mRNA of the survival motor neuron 2 (SMN2) gene in SMA patient-derived fibroblasts (demonstrated in vitro) | 65% | 33640427 |
| gene expression | Nusinersen augmented the expression of full-length SMN transcripts and proteins in SMA mice (observed in mouse model). | 65% | 40180233 |
| drug efficacy | Nusinersen treatment has led to dramatic improvements in respiratory failure and survival in SMA1 patients (observed in patient cohort) | 65% | 34921596 |
| drug efficacy | Nusinersen treatment resulted in an improvement, with increased mean scores between baseline (T0) and 12 months (T12) on both the Hammersmith Functional Motor Scale Expanded and the Revised Upper Limb Module (clinical trial result). | 65% | 34099377 |
| splicing event | Nusinersen binds to the pre-mRNA of SMN2 to prevent exon skipping and produce functional SMN protein. | 65% | 34515035 |
| splicing event | The combined treatment of SMA cells with sub-optimal doses of LBH589 and of an antisense oligonucleotide that mimic Nusinersen (ASO_ISSN1) elicits additive effects on SMN2 splicing (demonstrated in vitro). | 65% | 31811660 |
| drug efficacy | Nusinersen treatment improved motor scores as measured by the Hammersmith Functional Motor Scale-Expanded by 3.3% (p = .00005) over the 22-month study period (clinical trial result). | 65% | 33608138 |
| drug efficacy | Nusinersen treatment is associated with improvement in patient condition after four years in 54% of patients (observed in patient cohort). | 65% | 40451126 |
| splicing event | Nusinersen modifies premessenger RNA splicing of exon 7, leading to stable SMN protein expression. | 65% | 30617569 |
| biomarker | SMN circ4-2b-3 is a potential biomarker to predict the therapeutic response of type I SMA patients to Nusinersen (observed in patient cohort). | 65% | 39592557 |
| drug efficacy | Nusinersen treatment supports efficacy and safety in adult patients with SMA2 and SMA3 (observed in patient cohort). | 65% | 35527201 |
| drug efficacy | During the 18 months of nusinersen treatment, CK decreased (∆CK = -17.56%, p < 0.0001) (observed in patient cohort). | 64% | 33792208 |
| motor function | Grip strength increased by 44.9% (P = 0.031) in treatment-naive SMA patients treated with nusinersen via SIC (clinical trial result). | 64% | 34606118 |
| drug efficacy | Median symptom severity decreased during nusinersen treatment (median observational period 6.1 months, 0.5-16 months) from 3.7 to 3.3 MYMOP2 score points (p < 0.001) (clinical trial result). | 64% | 33960080 |
| drug efficacy | During the 18 months of nusinersen treatment, Crn slightly increased (∆Crn = +4.75%, p < 0.05) (observed in patient cohort). | 64% | 33792208 |
| splicing event | Nusinersen binds to intron splicing silencer-N1 (ISS-N1; a site present ten nucleotides down to the junction of exon 7 and intron 7), modulating the splicing of SMN2 pre-mRNA transcript to increase the inclusion of exon 7, thereby increasin... | 60% | 28755059 |
| drug efficacy | A significant clinical improvement was seen on all domains between T0 (prior to administration of nusinersen) and T1 (immediately before the first administration of maintenance doses, 6 months after the first administration of nusinersen) (... | 60% | 31939268 |
| motor function | Seventy-one per cent of nusinersen-treated infants versus 3% of infants in the control group were responders on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) measure of motor disability (clinic... | 60% | 31825542 |
| drug efficacy | Expedited therapy initiation, including reversible treatments like nusinersen or risdiplam, is recommended without waiting for the completion of the molecular testing, thus minimizing delays in crucial therapeutic interventions. | 59% | 40900970 |
| gene expression | Nusinersen induced modulation of apolipoprotein A1, apolipoprotein E, and transthyretin may support SMN improved-expression effects (observed in patient cohort). | 59% | 33919289 |
| drug efficacy | Nusinersen treatment was associated with stability in bulbar function in 40% of SMA type 1 patients with symptom onset >2 weeks and <3 months (observed in patient cohort). | 59% | 40504745 |
| safety | Nusinersen has the same safety and tolerability profile as in the clinical trials (clinical trial result). | 59% | 32456992 |
| biomarker | High-throughput CSF proteomics data prior and after nusinersen therapy provide possible biomarkers that may help in identification of more accurate prognosis | 59% | 32128827 |
Off-Target Findings (9)
T4: 4untiered: 5
| Target | Role | Tier | Boltz-2 iPTM | Chai-1 iPTM | Verdict |
|---|---|---|---|---|---|
| HSP70_NBD | OTHER | T4 | 0.774 | — | Low relevance |
| LRP4_propeller | OTHER | T4 | 0.767 | — | Low relevance |
| LIMK2_aC | OTHER | T4 | 0.616 | — | Low relevance |
| CHRNG_fetal | OTHER | T4 | 0.541 | — | Low relevance |
| CHRNA1_ECD | OTHER | — | 0.859 | — | — |
| PFN2 | SMA | — | 0.615 | — | — |
| STMN1 | SMA | — | 0.594 | — | — |
| KCNA2_pore | OTHER | — | 0.473 | — | — |
| PERP_ECL1 | OTHER | — | 0.452 | — | — |