SMA Research Platform

Evidence graph for Spinal Muscular Atrophy

Biology-first target discovery
API Docs·GitHub
Christian Fischer / Bryzant Labs
13,058Targets
453Trials
84Drugs
7Datasets
42,617Sources
48,024Claims
55,019Evidence
29,646Hypotheses

Drugs & Therapies

VALIDATED DATA
84 drugs

The SMA Research Platform tracks drugs across four relevance tiers — from officially approved SMA therapies to drugs approved for other conditions where computational or clinical evidence suggests SMA relevance. Every non-SMA-approved drug has a documented reason for inclusion.

Three FDA/EMA-approved treatments target the SMN pathway directly: nusinersen (antisense oligonucleotide, intrathecal), risdiplam (small-molecule splicing modifier, oral), and onasemnogene abeparvovec (AAV9 gene therapy, one-time IV). Pipeline drugs explore complementary approaches including muscle-enhancing (apitegromab, anti-myostatin), neuroprotective (fasudil, ROCK inhibition; riluzole, glutamate modulation), HDAC-mediated SMN2 upregulation (vorinostat), NMJ strengthening (pyridostigmine, amifampridine, argx-119, nmd-670), and oxidative-stress correction (dimethyl fumarate, omaveloxolone). Each drug entry links to DiffDock virtual screening results where available.

6
Approved for SMA
23
Investigational SMA
9
Approved / SMA interest
11
Approved (other)
28
Needs review
84
Total Drugs
31
Approved
13
Phase 2/3
31
Investigational
1
Discontinued
84 / 84

Approved for SMA

approved sma6

FDA/EMA-approved explicitly for spinal muscular atrophy.

NameBrandTypeStatusMechanismSMA relevance
intrathecal onasemnogene abeparvovecItvisma, OAV101 ITgene_therapyapprovedAAV9-delivered SMN1 gene replacement, single intrathecal injection. Non-IV route decouples dose from body weight (vs Zolgensma IV which is BW-limited).Phase 3 intrathecal route for Zolgensma (AAV9 SMN1 gene therapy) — improves CNS biodistribution in older SMA patients.detailinfo
nusinersenSpinrazaasoapprovedAntisense oligonucleotide targeting SMN2 pre-mRNA ISS-N1 to promote exon 7 inclusion.FDA-approved 2016 (Spinraza) — intrathecal ASO splicing modulator of SMN2 exon 7.detailinfo
nusinersen high-dose—asoapprovedHigher-dose formulation of nusinersen (Spinraza). ASO targeting SMN2 ISS-N1 at increased dosage for enhanced efficacy.High-dose intrathecal ASO splicing modulator of SMN2 exon 7; post-marketing variant of approved Spinraza.detailinfo
onasemnogene abeparvovecZolgensmagene_therapyapprovedAAV9-mediated gene replacement delivering functional SMN1. Single IV infusion.FDA-approved 2019 (Zolgensma) — AAV9 gene therapy delivering SMN1 cDNA.detailinfo
risdiplamEvrysdisplice_modifierapprovedSmall molecule SMN2 splicing modifier. Promotes exon 7 inclusion. Oral, crosses BBB.FDA-approved 2020 (Evrysdi) — oral small-molecule SMN2 splicing modulator.detailinfo
risdiplam tabletEvrysdi tabletsplice_modifierapprovedTablet formulation of risdiplam (Evrysdi). SMN2 splicing modifier for improved oral bioavailability.. Tablet formulation FDA-approved May 2024 (Genentech/Roche) for SMA patients ≥2 years and ≥20 kg.Oral tablet formulation of the FDA-approved SMN2 splicing modulator risdiplam (Evrysdi).detailinfo

Investigational for SMA

investigational sma23

In clinical trials or preclinical development for SMA.

NameBrandTypeStatusMechanismSMA relevance
arimoclomolMiplyffasmall_moleculeapprovedHydroxylamine HSP70/HSP90 co-inducer. Preserves NMJ structure in SOD1-G93A ALS mice (PMID 22591194). Approved for Niemann-Pick type C (2024). Candidate SMA adjunct.Phase 3 HSP70 co-inducer (approved 2024 for Niemann-Pick C as Miplyffa); investigational in SMA and related motor-neuron diseases via the proteostasis axis.detailinfo
salanersenBIIB115, salanersenasophase3Novel SMN2 splice-modifier ASO with improved backbone chemistry vs nusinersen. Designed for once-yearly IV dosing; promotes SMN2 exon 7 inclusion → boosts full-length SMN.Phase 3 SMN2-targeting antisense oligonucleotide (Ionis) — next-generation Spinraza successor in SMA.detailinfo
nmd-670—small_moleculephase2First-in-class ClC-1 chloride channel inhibitor. Partial block stabilizes muscle membrane charge → potentiates neuromuscular transmission. Originally validated in myasthenia gravis Phase 2.Phase 1/2 ClC-1 chloride-channel inhibitor (NMD Pharma) — NMJ-strength enhancer in neuromuscular disease, tested in SMA.detailinfo
reldesemtiv—small_moleculephase2Fast skeletal muscle troponin activator. Enhances muscle force production.Phase 2 fast-skeletal-muscle troponin activator (Cytokinetics) — evaluated in SMA for muscle-contraction enhancement.detailinfo
salbutamolVentolin, Proventilsmall_moleculephase2β2-adrenergic receptor agonist. Increases SMN2 full-length mRNA in SMA fibroblasts (~2-fold). Improves respiratory strength in SMA type II (PMID 40410501).β2-adrenergic agonist (approved asthma drug); Phase 2 in SMA for SMN2 transcription upregulation and muscle performance.detailinfo
taldefgrobep alfaBHV-2000antibodyphase2Anti-myostatin antibody. Inhibits myostatin to promote muscle growth and prevent atrophy.Phase 2 myostatin/activin pathway modulator (Biohaven) — muscle-enhancement strategy tested in SMA.detailinfo
adimanebartARGX-119, adimanebartantibodyphase1First-in-class humanized agonist IgG4 antibody binding MuSK extracellular domain. Activates MuSK → drives AChR clustering and NMJ stabilization. Differs from MG anti-MuSK antagonists.Phase 1 anti-MuSK agonist antibody (argenx) — NMJ-stabilizing biologic relevant to SMA A1-NMJ axis.detailinfo
biogen-ionis novel aso—asophase1Next-generation antisense oligonucleotide for SMA. Novel ASO with improved potency or delivery.Phase 1 antisense oligonucleotide from Biogen-Ionis SMA program — SMN2 splicing-modulator class.detailinfo
cinnatrarx p38a inhibitor—small_moleculephase1p38α MAPK inhibitor. Targets stress-kinase signaling implicated in SMA motor neuron loss. Spinout from Columbia University / NU collaboration.Phase 1 p38α MAPK inhibitor (Cinnatrarx) under evaluation for neurodegeneration including SMA motor-neuron stress response.detailinfo
triheptanoinDojolvismall_moleculeinvestigationalAnaplerotic substrate for energy metabolism. Positive in SMND7 mice (2021) — both survival and motor.. NOTE: Approved 2020 as Dojolvi (Ultragenyx) for LC-FAOD (long-chain fatty acid oxidation disorders); SMA use is off-label/investigational.Odd-chain triglyceride (approved Dojolvi for LC-FAOD); investigational in SMA for mitochondrial-energetics and motor-neuron metabolic support.detailinfo
e1-1022—small_moleculepreclinicalPreclinical SMA therapeutic candidate. Dual molecule approach.Preclinical small-molecule Bryzant/external SMA program compound (identifier E1-1022).detailinfo
ki-696—small_moleculepreclinicalNon-covalent KEAP1 Kelch-domain PPI inhibitor, Kd = 1.3 nM. Reference tool compound for pure occupancy-based NRF2 activation (distinguishes from electrophilic triterpenoids).Preclinical KEAP1-Nrf2 activator (KI-696) — tool compound relevant to SMA oxidative-stress axis (B3).detailinfo
marinus calcium channel modifier—small_moleculepreclinicalCalcium channel modifier targeting calcium homeostasis in motor neurons.Preclinical Marinus Pharmaceuticals calcium-channel modifier under evaluation for SMA bioelectric axis.detailinfo
paxis protein synthesis enhancer—small_moleculepreclinicalProtein synthesis enhancer targeting translational upregulation of SMN protein production.Preclinical protein-synthesis-enhancer program (Paxis) under evaluation for SMA motor-neuron translation support.detailinfo
voyage aav gene therapy—gene_therapypreclinicalAAV gene therapy delivering codon-optimized SMN1 cDNA. Uses Voyager TRACER platform (target-specific in vivo capsid evolution) for enhanced CNS/spinal-cord tropism vs first-gen AAV9. Novartis license 2022.Preclinical AAV gene-therapy program (Voyage Therapeutics) with SMN1 delivery rationale; not yet approved.detailinfo
3,5-dichloro-2-hydroxy-N-(2-methoxy-5-phenylphenyl)benzenesulfonamide—small_molecule——Preclinical tool sulfonamide compound from Bryzant SMA chemoinformatics library.detailinfo
7b-cis—small_molecule——Preclinical Bryzant/internal research compound (identifier 7B-cis).detailinfo
COT-10b—small_molecule——Preclinical Bryzant/internal research compound (identifier COT-10B).detailinfo
Chemistry 2804—small_molecule——Preclinical Bryzant/internal chemistry pipeline compound (identifier Chemistry 2804).detailinfo
MN25_ROCK2—small_molecule——Bryzant preclinical ROCK2-directed small molecule (MN25) — ACTIN-pathway axis for SMA motor neurons.detailinfo
S1122—small_molecule——Preclinical Bryzant/internal research compound (identifier S1122).detailinfo
arg-a1-22 BRD-K91349888—small_molecule——Bryzant ARG-A1-22 (Broad BRD-K91349888) — preclinical candidate from SMA repurposing screen.detailinfo
olesoxime—small_moleculediscontinuedMitochondrial function, cholesterol binding. Positive in SMND7 mice (2014). Both survival + motor function improved.. DISCONTINUED 2018 (Roche) — Phase 3 OLEOS failed futility analysis; development halted.Mitochondrial permeability-transition modulator (Roche); previously Phase 3 in SMA Type 2/3 — development discontinued after missing co-primary endpoint.detailinfo

Approved elsewhere, SMA research interest

off label reported sma9

Approved for other indications; computational or published evidence suggests SMA relevance.

NameBrandTypeStatusMechanismSMA relevance
FLUVASTATIN—small_moleculeapproved—Approved statin for cholesterol. Pedotti 2014 SMA-statin splicing link; included for axis consistency.detailinfo
SIMVASTATIN—small_moleculeapproved—Approved statin for cholesterol. Pedotti 2014 SMA-statin splicing link; Bryzant LINCS signature-reversal evidence.detailinfo
amifampridineFirdapse, Ruzurgismall_moleculeapproved3,4-diaminopyridine. Blocks presynaptic Kv channels, prolongs action potential, enhances ACh release. Off-label NMJ symptomatic therapy in SMA.Approved 4-aminopyridine (Firdapse) for Lambert-Eaton Myasthenic Syndrome (LEMS). Potassium-channel blocker; investigated in SMA for NMJ strengthening (B1-bioelectric axis).detailinfo
atorvastatin—small_moleculeapproved—Approved statin for cholesterol. Pedotti et al. 2014 report statins modulate SMN2 splicing; Bryzant LINCS 2026-04-21 analysis shows reversal of the SMA-MN signature.detailinfo
riluzole—small_moleculeapprovedGlutamate antagonist. Positive in SMND7 mice (2008). Only validated DiffDock hit (+0.082 at 20 poses).Approved for ALS (glutamate modulator). Bryzant 2026-04-21 flagship finding: riluzole × LIMK2-αC Chai-1 iPTM 0.767 orthogonally confirmed — pending 3-LLM gate + selectivity panel before external claim.detailinfo
vorinostat—small_moleculeapproved—FDA-approved 2006 (Zolinza) for cutaneous T-cell lymphoma. HDAC inhibitor; preclinical evidence for SMN2 transcription upregulation in SMA fibroblasts and motor neurons.detailinfo
fasudilHA-1077, Erilsmall_moleculephase2ROCK1/2 inhibitor. Improves NMJ morphology and survival in SMNΔ7 mice (Bowerman 2012). Approved for cerebral vasospasm in Japan. Our Track 1 lead — baseline 100 ns apo-ROCK2 MD published 2026-04-12.Approved in Japan for cerebral vasospasm. Pan-ROCK inhibitor; Bryzant computational evidence supports ROCK-LIMK2-CFL2 (ACTIN-pathway) axis relevance to SMA motor neurons.detailinfo
pyridostigmineMestinonsmall_moleculephase2Acetylcholinesterase inhibitor. Improves neuromuscular transmission at the NMJ.Approved acetylcholinesterase inhibitor for Myasthenia Gravis. NMJ-modulator relevant to the A1-NMJ SMA axis; Phase 2 in pediatric SMA for muscle-fatigue symptom relief.detailinfo
4AP—small_molecule——Approved 4-aminopyridine (Firdapse) for LEMS. Potassium-channel blocker; Bryzant B1-bioelectric SMA relevance.detailinfo

Approved for other indications

approved other11

Tracked for scientific completeness (controls, chemoinformatics); no known SMA link.

NameBrandTypeStatusMechanismSMA relevance
Amyleine hydrochloride—small_moleculeapproved—Historical local anesthetic (early-20th-century clinical use). No SMA relevance; ingested for chemoinformatics coverage.detailinfo
KETOPROFEN—small_moleculeapproved—Approved NSAID for pain and inflammation. No SMA relevance.detailinfo
Loperamide hydrochloride—small_moleculeapproved—Approved µ-opioid antidiarrheal (Imodium). No SMA relevance; ingested for chemoinformatics coverage.detailinfo
Valdecoxib—small_moleculeapproved—Approved COX-2 inhibitor (Bextra, withdrawn 2005 for cardiovascular events). No SMA relevance.detailinfo
aspirin—small_moleculeapproved—Approved OTC NSAID / antiplatelet. No SMA-specific rationale; ingested as computational control.detailinfo
ataluren—small_moleculeapproved—Approved (EMA) for Duchenne muscular dystrophy nonsense-mutation readthrough (Translarna). Not SMA-specific; ingested by Bryzant saturator as NMD-adjacent drug.detailinfo
mitoxantrone—small_moleculeapproved—Approved chemotherapeutic (AML, prostate) and multiple sclerosis drug (Novantrone). No SMA relevance.detailinfo
risperidone—small_moleculeapproved—Approved atypical antipsychotic for schizophrenia and bipolar mania. Bryzant computational comparator to Haloperidol only; no direct SMA claim.detailinfo
ziconotide—small_moleculeapproved—Approved intrathecal N-type calcium-channel blocker for refractory chronic pain (Prialt). No SMA relevance.detailinfo
GBR 12909 dihydrochloride—small_moleculeinvestigational—Dopamine reuptake inhibitor research tool compound (Vanoxerine); not clinically approved. No SMA relevance.detailinfo
niguldipine hydrochloride—small_moleculeinvestigational—Dihydropyridine L-type calcium channel blocker research tool. No SMA relevance.detailinfo

Needs review

needs review35

Auto-classification fallback — awaiting human review.

NameBrandTypeStatusMechanismSMA relevance
Dimethyl FumarateTecfiderasmall_moleculeapprovedNRF2 activator—detailinfo
HaloperidolHaldol, Serenacesmall_moleculeapprovedD2 dopamine antagonist - SMA repurposed via Menduti 2026.—detailinfo
Melatonin—small_moleculeapprovedPineal hormone — circadian, mitochondrial biogenesis, browning of WAT—detailinfo
N-Acetylcysteine—small_moleculeapprovedGlutathione precursor / antioxidant—detailinfo
N-acetylcysteineMucomyst, Acetadotesmall_moleculeapprovedGlutathione precursor + direct antioxidant. FDA approved for paracetamol overdose, mucolytic. Validated in SMNΔ7 cortical neuron rescue (Stanga O11 Budapest 2026 — alongside 4-AP and Valproic Acid).Validated in SMA cortical neuron rescue (Stanga O11) + general antioxidantdetailinfo
OmaveloxoloneSkyclaryssmall_moleculeapprovedNRF2 activator (KEAP1 inhibitor)—detailinfo
dimethyl fumarateTecfiderasmall_moleculeapprovedFumarate ester; active metabolite monomethyl fumarate covalently modifies KEAP1 Cys151 to activate NRF2. FDA-approved for MS. Candidate SMA redox adjunct.Approved for multiple sclerosis (Tecfidera). Nrf2 pathway activator; Bryzant investigates for SMA oxidative-stress axis (B3).detailinfo
givinostat—small_moleculeapprovedHDAC class I + IIb inhibitor. FDA approved 2024-03-21 for Duchenne Muscular Dystrophy (Duvyzat, Italfarmaco). SMA repurposing candidate per Osseni 2026.—detailinfo
omaveloxoloneSkyclaryssmall_moleculeapprovedRTA-408. Semi-synthetic triterpenoid NRF2 activator via covalent KEAP1 Cys151 modification. FDA-approved for Friedreich ataxia (2023) — closest analog for SMA repurposing.NRF2 activator class — Wirth O16 SMA fibroblast rescue (Budapest 2026)detailinfo
Bardoxolone Methyl—small_moleculephase3NRF2 activator—detailinfo
Salanersen—asophase3ASO splice modulator (SMN2 ISS-N1, BIIB115 backbone)—detailinfo
apitegromabSRK-015, apitegromabantibodyphase3anti-myostatin (GDF8) monoclonal antibody — muscle-axis SMA therapy. BLA accepted FDA 2026-05-08, PDUFA 2026-09-30.—detailinfo
bardoxolone methylCDDO-Me, RTA-402small_moleculephase3Synthetic oleanolic acid triterpenoid. Potent NRF2 activator via KEAP1 Cys151/Cys288 Michael addition. Clinical trials in CKD, PH, cancer. Candidate SMA redox adjunct (Vrettou Cologne 2026 O16).Phase 3 Nrf2-KEAP1 activator (Reata) for chronic kidney disease and Friedreich ataxia. Mechanistic overlap with SMA oxidative-stress axis (B3).detailinfo
itvisma—gene_therapyphase3AAV9-SMN1 gene replacement (extended label for older SMA patients) — Novartis. EMA CHMP positive opinion 2026-04-23, EC decision pending.—detailinfo
branaplam—splice_modifierphase2Small-molecule SMN2 splice modulator. Stabilizes U1 snRNP binding at SMN2 exon 7 5'SS to promote inclusion.—detailinfo
ARGX-119—antibodyphase1Anti-MuSK agonist monoclonal antibody. Coadministration with SMN2 splice modulator (SMN-C3) improves voluntary locomotion + masseter force in SMNΔ7 mouse model (Coppejans O28 Budapest 2026). Combination strategy: SMN-restore + NMJ-target.—detailinfo
Sulforaphane—small_moleculeinvestigationalNRF2 activator (natural product)—detailinfo
BPN15477—splice_modifierpreclinicalSmall-molecule splice modulator candidate. Modulates pseudoexon inclusion; explored as splice-correction tool molecule.—detailinfo
aurimmed sma small moleculeAurimMed-SMAsmall_moleculepreclinicalMechanism class undisclosed. Privileged-structure platform screened for SMN2 expression activity (collaboration with Nemours Alfred I. DuPont Hospital for Children, Sept 2013).—detailinfo
chembl1303998—small_moleculepreclinicalphenyl-cyclopentane carboxamide; SMN1/SMN2 binder pchembl=8.55, BBB=0.97—detailinfo
chembl1466254—small_moleculepreclinicaltoluamide-piperidine-morpholine; SMN1/SMN2 binder pchembl=8.66, BBB=0.97—detailinfo
chembl1483828—small_moleculepreclinicalmethoxybenzene sulfonamide; SMN1/SMN2 binder pchembl=8.80, BBB=0.74—detailinfo
chembl1528069—small_moleculepreclinicalpyrazol-1-yl-aminopyrimidine; SMN1/SMN2 binder pchembl=8.55, BBB=0.90—detailinfo
chembl1577858—small_moleculepreclinicalbenzothiazole sulfonyl carboxamide; SMN1/SMN2 binder pchembl=8.55, BBB=0.88—detailinfo
chembl475244—small_moleculepreclinicalbiphenyl piperidine carboxamide; SMN1/SMN2 binder pchembl=8.55, BBB=0.95—detailinfo
e1v1.11E1v1.11, Element-1 ASOasopreclinicalPhosphorodiamidate morpholino (PMO) ASO that blocks Element 1 (E1), an intronic repressor in SMN2 pre-mRNA, de-repressing exon 7 inclusion. Mechanism distinct from nusinersen (which blocks 3' splice site).—detailinfo
gv-58GV-58small_moleculepreclinicalSelective Cav2 calcium-channel gating modifier. Stabilizes open state → enhances Ca2+ influx into motor nerve terminals → boosts ACh release. In severe SMA mice, GV-58 + DAP combination restored quantal content ~44% and improved muscle strength.—detailinfo
melatonin—small_moleculepreclinicalPineal hormone. Bowerman (Keele) O39 SMA Congress 2026 shows improved motor phenotype and survival in SMA mice and worms. Inexpensive repurposing candidate.Bowerman 2026 (Keele) preclinical melatonin in Smn2B/- mouse + C. elegansdetailinfo
mmp_1303998_2pyridyl—small_moleculepreclinicalMMP variant of CHEMBL1303998 (phenyl -> 2-pyridyl)—detailinfo
mmp_1303998_2thienyl—small_moleculepreclinicalMMP variant of CHEMBL1303998 (phenyl -> 2-thienyl)—detailinfo
mmp_1303998_3pyridyl—small_moleculepreclinicalMMP variant of CHEMBL1303998 (phenyl -> 3-pyridyl)—detailinfo
mmp_1303998_ether—small_moleculepreclinicalMMP variant of CHEMBL1303998 (CH2 -> O ether bioisostere)—detailinfo
mmp_1303998_glycol—small_moleculepreclinicalMMP variant of CHEMBL1303998 (propylene -> ethylene-glycol bioisostere)—detailinfo
praxis biotech sma protein synthesisPraxis-Biotech-SMAsmall_moleculepreclinicalProtein-synthesis modulator class. Unknown specific target. Likely candidate pathways: eIF2α phosphorylation or mTOR signaling, but not confirmed publicly.—detailinfo
sulforaphane—small_moleculepreclinicalNatural isothiocyanate from cruciferous vegetables. Direct KEAP1 Cys151 modifier, activates NRF2-ARE. Inexpensive tool compound + candidate repurposing for SMA redox rescue.NRF2 axis — natural-product activatordetailinfo
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