Teaching An Old Drug New Tricks: Repositioning Strategies for Spinal Muscular atrophy

References

• KolbSJ, KisselJT. Spinal muscular atrophy. Neurol. Clin.33(4), 831–846 (2015).
   PubMed Web of Science ®Google Scholar
• PriorTW, SnyderPJ, RinkBDet al.Newborn and carrier screening for spinal muscular atrophy. Am. J. Med. Genet. A152A(7), 1608–1616 (2010).
   PubMed Web of Science ®Google Scholar
• LefebvreS, BürglenL, ReboulletSet al.Identification and characterization of a spinal muscular atrophy-determining gene. Cell80(1), 155–165 (1995).
   PubMed Web of Science ®Google Scholar
• SinghRN, HowellMD, OttesenEW, SinghNN. Diverse role of survival motor neuron protein. Biochim. Biophys. Acta Gene Regul. Mech.1860(3), 299–315 (2017).
   PubMed Web of Science ®Google Scholar
• KashimaT, ManleyJL. A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy. Nat. Genet.34(4), 460–463 (2003).
   PubMed Web of Science ®Google Scholar
• MonaniUR, LorsonCL, ParsonsDWet al.A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum. Mol. Genet.8(7), 1177–1183 (1999).
   PubMed Web of Science ®Google Scholar
• SinghNK, SinghNN, AndrophyEJ, SinghRN. Splicing of a critical exon of human survival motor neuron is regulated by a unique silencer element located in the last intron. Mol. Cell. Biol.26(4), 1333–1346 (2006).
   PubMed Web of Science ®Google Scholar
• FinkelRS, MercuriE, DarrasBTet al.Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N. Engl. J. Med.377(18), 1723–1732 (2017).
   PubMed Web of Science ®Google Scholar
• MontesJ, McDermottMP, MirekEet al.Ambulatory function in spinal muscular atrophy: age-related patterns of progression. PLoS ONE13(6), e0199657 (2018).
   PubMed Web of Science ®Google Scholar
• GidaroT, ServaisL. Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps. Dev. Med. Child Neurol.61(1), 19–24 (2019).
   PubMed Web of Science ®Google Scholar
• BoardmanFK, YoungPJ, GriffithsFE. Newborn screening for spinal muscular atrophy: the views of affected families and adults. Am. J. Med. Genet. A173(6), 1546–1561 (2017).
   PubMed Web of Science ®Google Scholar
• MousaMA, AriaDJ, SchaeferCMet al.A comprehensive institutional overview of intrathecal nusinersen injections for spinal muscular atrophy. Pediatr. Radiol.48(12), 1797–1805 (2018).
   PubMed Web of Science ®Google Scholar
• NICE. Nusinersen for treating spinal muscular atrophy. https://www.nice.org.uk/guidance/GID-TA10281/documents/appraisal-consultation-document
   Google Scholar
• Al-ZaidyS, PickardAS, KothaKet al.Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy. Pediatr. Pulmonol.54(2), 179–185 (2019).
   PubMed Web of Science ®Google Scholar
• MaloneDC, DeanR, ArjunjiRet al.Cost-effectiveness analysis of using onasemnogene abeparvocec (AVXS-101) in spinal muscular atrophy type 1 patients. J. Mark. Access Health Policy7(1), 1601484 (2019).
   PubMedGoogle Scholar
• DicksonM, GagnonJP. The cost of new drug discovery and development. Discov. Med.4(22), 172–179 (2004).
   PubMedGoogle Scholar
• AshburnTT, ThorKB. Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov.3(8), 673–683 (2004).
   PubMed Web of Science ®Google Scholar
• GraulAI, CrucesE, StringerM. The year's new drugs & biologics, 2014: part I. Drugs Today51(1), 37–87 (2015).
   PubMed Web of Science ®Google Scholar
• LiJ, ZhengS, ChenB, ButteAJ, SwamidassSJ, LuZ. A survey of current trends in computational drug repositioning. Brief Bioinform.17(1), 2–12 (2016).
   PubMed Web of Science ®Google Scholar
• RojasLBA, GomesMB. Metformin: an old but still the best treatment for type 2 diabetes. Diabetol. Metab. Syndr.5, 6 (2013).
   PubMed Web of Science ®Google Scholar
• HeX, EstevaFJ, EnsorJ, HortobagyiGN, LeeM-H, YeungS-CJ. Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer. Ann. Oncol.23(7), 1771–1780 (2012).
   PubMed Web of Science ®Google Scholar
• ChenT-M, LinC-C, HuangP-T, WenC-F. Metformin associated with lower mortality in diabetic patients with early stage hepatocellular carcinoma after radiofrequency ablation. J. Gastroenterol. Hepatol.26(5), 858–865 (2011).
   PubMed Web of Science ®Google Scholar
• HadadS, IwamotoT, JordanLet al.Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res. Treat.128(3), 783–794 (2011).
   PubMed Web of Science ®Google Scholar
• LaskovI, DrudiL, BeauchampM-Cet al.Anti-diabetic doses of metformin decrease proliferation markers in tumors of patients with endometrial cancer. Gynecol. Oncol.134(3), 607–614 (2014).
   PubMed Web of Science ®Google Scholar
• RidingsJE. The thalidomide disaster, lessons from the past. Methods Mol. Biol.947, 575–586 (2013).
   PubMedGoogle Scholar
• HeP, ChengX, StaufenbielM, LiR, ShenY. Long-term treatment of thalidomide ameliorates amyloid-like pathology through inhibition of β-secretase in a mouse model of Alzheimer's disease. PLoS ONE8(2), e55091 (2013).
   PubMed Web of Science ®Google Scholar
• BrieseM, EsmaeiliB, SattelleDB. Is spinal muscular atrophy the result of defects in motor neuron processes?Bioessays27(9), 946–957 (2005).
   PubMed Web of Science ®Google Scholar
• BowermanM, BeckerCG, Yáñez-MuñozRJet al.Therapeutic strategies for spinal muscular atrophy: SMN and beyond. Dis. Model Mech.10(8), 943–954 (2017).
   PubMed Web of Science ®Google Scholar
• Donlin-AspPG, BassellGJ, RossollW. A role for the survival of motor neuron protein in mRNP assembly and transport. Curr. Opin. Neurobiol.39, 53–61 (2016).
   PubMed Web of Science ®Google Scholar
• KongL, WangX, ChoeDWet al.Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy mice. J. Neurosci.29(3), 842–851 (2009).
   PubMed Web of Science ®Google Scholar
• HenselN, ClausP. The actin cytoskeleton in SMA and ALS: how does it contribute to motoneuron degeneration?Neuroscientist24(1), 54–72 (2018).
   PubMed Web of Science ®Google Scholar
• van BergeijkJ, Rydel-KöneckeK, GrotheC, ClausP. The spinal muscular atrophy gene product regulates neurite outgrowth: importance of the C terminus. FASEB J.21(7), 1492–1502 (2007).
   PubMed Web of Science ®Google Scholar
• TarabalO, Caraballo-MirallesV, Cardona-RossinyolAet al.Mechanisms involved in spinal cord central synapse loss in a mouse model of spinal muscular atrophy. J. Neuropathol. Exp. Neurol.73(6), 519–535 (2014).
   PubMed Web of Science ®Google Scholar
• StutzmannJM, WahlF, PrattJet al.Neuroprotective profile of riluzole in in vivo models of acute neurodegenerative diseases. CNS Drug Rev.3(1), 83–101 (1997).
   Google Scholar
• DimitriadiM, KyeMJ, KallooG, YersakJM, SahinM, HartAC. The neuroprotective drug riluzole acts via small conductance Ca2+-activated K+ channels to ameliorate defects in spinal muscular atrophy models. J. Neurosci.33(15), 6557–6562 (2013).
   PubMed Web of Science ®Google Scholar
• FáveroFM, VoosMC, de CastroI, CaromanoFA, OliveiraASB. Epidemiological and clinical factors impact on the benefit of riluzole in the survival rates of patients with ALS. Arq. Neuropsiquiatr.75(8), 515–522 (2017).
   PubMed Web of Science ®Google Scholar
• RussmanBS, IannacconeST, SamahaFJ. A Phase I trial of riluzole in spinal muscular atrophy. Arch. Neurol.60(11), 1601–1603 (2003).
   PubMed Web of Science ®Google Scholar
• AbbaraC, EstournetB, LacomblezLet al.Riluzole pharmacokinetics in young patients with spinal muscular atrophy. Br. J. Clin. Pharmacol.71(3), 403–410 (2011).
   PubMed Web of Science ®Google Scholar
• FinbergJP, LamensdorfI, CommissiongJW, YoudimMB. Pharmacology and neuroprotective properties of rasagiline. J. Neural Transm. Suppl.48, 95–101 (1996).
   PubMedGoogle Scholar
• StudentAK, EdwardsDJ. Subcellular localization of types A and B monoamine oxidase in rat brain. Biochem. Pharmacol.26(24), 2337–2342 (1977).
   PubMed Web of Science ®Google Scholar
• EdmondsonDE, BindaC, WangJ, UpadhyayAK, MatteviA. Molecular and mechanistic properties of the membrane-bound mitochondrial monoamine oxidases. Biochemistry48(20), 4220–4230 (2009).
   PubMed Web of Science ®Google Scholar
• TabakmanR, LechtS, LazaroviciP. Neuroprotection by monoamine oxidase B inhibitors: a therapeutic strategy for Parkinson's disease?Bioessays26(1), 80–90 (2004).
   PubMed Web of Science ®Google Scholar
• MallajosyulaJK, KaurD, ChintaSJet al.MAO-B elevation in mouse brain astrocytes results in Parkinson's pathology. PLoS ONE3(2), (2008). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2229649/
   PubMed Web of Science ®Google Scholar
• BarohnR, StatlandJ, MooreDet al.Rasagiline for the treatment of ALS: a randomized controlled study (S27.001). Neurology88(16 Suppl.), S27.001 (2017).
   Google Scholar
• LudolphAC, SchusterJ, DorstJet al.Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, Phase II trial. Lancet Neurol.17(8), 681–688 (2018).
   PubMed Web of Science ®Google Scholar
• StatlandJM, MooreD, WangYet al.Rasagiline for amyotrophic lateral sclerosis: a randomized, controlled trial. Muscle Nerve59(2), 201–207 (2019).
   PubMed Web of Science ®Google Scholar
• FarfánLabonne BE, GutiérrezM, Gómez-QuirozLEet al.Acetaldehyde-induced mitochondrial dysfunction sensitizes hepatocytes to oxidative damage. Cell Biol. Toxicol.25(6), 599–609 (2009).
   PubMed Web of Science ®Google Scholar
• KaludercicN, CarpiA, NagayamaTet al.Monoamine oxidase B prompts mitochondrial and cardiac dysfunction in pressure overloaded hearts. Antioxid. Redox Signal.20(2), 267–280 (2014).
   PubMed Web of Science ®Google Scholar
• IslamMT. Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol. Res.39(1), 73–82 (2017).
   PubMed Web of Science ®Google Scholar
• WoodPL, KhanMA, KulowSR, MahmoodSA, MoskalJR. Neurotoxicity of reactive aldehydes: the concept of “aldehyde load” as demonstrated by neuroprotection with hydroxylamines. Brain Res.1095(1), 190–199 (2006).
   PubMed Web of Science ®Google Scholar
• MillerN, ShiH, ZelikovichAS, MaY-C. Motor neuron mitochondrial dysfunction in spinal muscular atrophy. Hum. Mol. Genet.25(16), 3395–3406 (2016).
   PubMed Web of Science ®Google Scholar
• CalsolaroV, EdisonP. Neuroinflammation in Alzheimer's disease: current evidence and future directions. Alzheimers Dement.12(6), 719–732 (2016).
   PubMed Web of Science ®Google Scholar
• NayakD, RothTL, McGavernDB. Microglia development and function. Annu. Rev. Immunol.32, 367–402 (2014).
   PubMed Web of Science ®Google Scholar
• von BernhardiR, EugenínJ. Microglial reactivity to beta-amyloid is modulated by astrocytes and proinflammatory factors. Brain Res.1025(1–2), 186–193 (2004).
   PubMed Web of Science ®Google Scholar
• KrsticD, MadhusudanA, DoehnerJet al.Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. J. Neuroinflammation9, 151 (2012).
   PubMed Web of Science ®Google Scholar
• ZrzavyT, HöftbergerR, BergerTet al.Pro-inflammatory activation of microglia in the brain of patients with sepsis. Neuropathol. Appl. Neurobiol.45(3), 278–290 (2019).
   PubMed Web of Science ®Google Scholar
• von BernhardiR, Eugenín-vonBernhardi L, EugenínJ. Microglial cell dysregulation in brain aging and neurodegeneration. Front. Aging Neurosci.7, 124 (2015).
   PubMed Web of Science ®Google Scholar
• WalkerDG, TangTM, LueL-F. Studies on colony stimulating factor receptor-1 and ligands colony stimulating factor-1 and interleukin-34 in Alzheimer's disease brains and human microglia. Front. Aging Neurosci.9, 244 (2017).
   PubMed Web of Science ®Google Scholar
• MurphyGM, ZhaoF, YangL, CordellB. Expression of macrophage colony-stimulating factor receptor is increased in the AβPPV717F transgenic mouse model of Alzheimer's disease. Am. J. Pathol.157(3), 895–904 (2000).
   PubMed Web of Science ®Google Scholar
• ErblichB, ZhuL, EtgenAM, DobrenisK, PollardJW. Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. PLoS ONE6(10), e26317 (2011).
   PubMed Web of Science ®Google Scholar
• LemmonMA, SchlessingerJ. Cell signaling by receptor tyrosine kinases. Cell141(7), 1117–1134 (2010).
   PubMed Web of Science ®Google Scholar
• D'allardD, GayJ, DescarpentriesCet al.Tyrosine kinase inhibitors induce down-regulation of c-Kit by targeting the ATP pocket. PLoS ONE8(4), e60961 (2013).
   PubMed Web of Science ®Google Scholar
• DubreuilP, LetardS, CiufoliniMet al.Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS ONE4(9), e7258 (2009).
   PubMed Web of Science ®Google Scholar
• PietteF, BelminJ, VincentHet al.Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's disease: a randomised, placebo-controlled Phase II trial. Alzheimers Res. Ther.3(2), 16 (2011).
   PubMed Web of Science ®Google Scholar
• TriasE, IbarburuS, Barreto-NúñezRet al.Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. J. Neuroinflammation13(1), 177 (2016).
   PubMedGoogle Scholar
• MoraJS, HermineO. Masitinib as an add-on therapy to riluzole is safe and effective in the treatment of amyotrophic lateral sclerosis (ALS). J. Neurol. Sci.381, 183 (2017).
   Web of Science ®Google Scholar
• PapadimitriouD, LeVerche V, JacquierA, IkizB, PrzedborskiS, ReDB. Inflammation in ALS and SMA: sorting out the good from the evil. Neurobiol. Dis.37(3), 493–502 (2010).
   PubMed Web of Science ®Google Scholar
• WanB, FengP, GuanZ, ShengL, LiuZ, HuaY. A severe mouse model of spinal muscular atrophy develops early systemic inflammation. Hum. Mol. Genet.27(23), 4061–4076 (2018).
   PubMed Web of Science ®Google Scholar
• MartinJE, NguyenTT, GrunseichCet al.Decreased motor neuron support by SMA astrocytes due to diminished MCP1 secretion. J. Neurosci.37(21), 5309–5318 (2017).
   PubMed Web of Science ®Google Scholar
• RindtH, FengZ, MazzasetteCet al.Astrocytes influence the severity of spinal muscular atrophy. Hum. Mol. Genet.24(14), 4094–4102 (2015).
   PubMed Web of Science ®Google Scholar
• OhuchiK, FunatoM, YoshinoYet al.Notch signaling mediates astrocyte abnormality in spinal muscular atrophy model systems. Sci. Rep.9(1), 3701 (2019).
   PubMedGoogle Scholar
• BoidoM, VercelliA. Neuromuscular junctions as key contributors and therapeutic targets in spinal muscular atrophy. Front. Neuroanat. (2016). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737916/
   PubMed Web of Science ®Google Scholar
• YoshidaM, KitaokaS, EgawaNet al.Modeling the early phenotype at the neuromuscular junction of spinal muscular atrophy using patient-derived iPSCs. Stem Cell Rep.4(4), 561–568 (2015).
   PubMed Web of Science ®Google Scholar
• WatermanSA, LangB, Newsom-DavisJ. Effect of Lambert-Eaton myasthenic syndrome antibodies on autonomic neurons in the mouse. Ann. Neurol.42(2), 147–156 (1997).
   PubMed Web of Science ®Google Scholar
• MaddisonP, Newsom-DavisJ, MillsKR. Effect of 3,4-diaminopyridine on the time course of decay of compound muscle action potential augmentation in the Lambert–Eaton myasthenic syndrome. Muscle Nerve21(9), 1196–1198 (1998).
   PubMed Web of Science ®Google Scholar
• OhSJ, ShcherbakovaN, Kostera-PruszczykAet al.Amifampridine phosphate (Firdapse(®)) is effective and safe in a Phase III clinical trial in LEMS. Muscle Nerve53(5), 717–725 (2016).
   PubMed Web of Science ®Google Scholar
• JablonkaS, BeckM, LechnerBD, MayerC, SendtnerM. Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy. J. Cell Biol.179(1), 139–149 (2007).
   PubMed Web of Science ®Google Scholar
• MorschM, ReddelSW, GhazanfariN, ToykaKV, PhillipsWD. Pyridostigmine but not 3,4-diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle-specific kinase autoantibody. J. Physiol. (Lond.)591(10), 2747–2762 (2013).
   Google Scholar
• BonannoS, PasanisiMB, FrangiamoreRet al.Amifampridine phosphate in the treatment of muscle-specific kinase myasthenia gravis: a Phase IIb, randomized, double-blind, placebo-controlled, double crossover study. SAGE Open Med.6, 2050312118819013 (2018).
   PubMedGoogle Scholar
• MoriS, KishiM, KuboSet al.3,4-Diaminopyridine improves neuromuscular transmission in a MuSK antibody-induced mouse model of myasthenia gravis. J. Neuroimmunol.245(1–2), 75–78 (2012).
   PubMed Web of Science ®Google Scholar
• BowenDC, ParkJS, BodineSet al.Localization and regulation of MuSK at the neuromuscular junction. Dev. Biol.199(2), 309–319 (1998).
   PubMed Web of Science ®Google Scholar
• HochW, McConvilleJ, HelmsS, Newsom-DavisJ, MelmsA, VincentA. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat. Med.7(3), 365–368 (2001).
   PubMed Web of Science ®Google Scholar
• ValenzuelaDM, StittTN, DiStefanoPSet al.Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle, at the neuromuscular junction, and after injury. Neuron15(3), 573–584 (1995).
   PubMed Web of Science ®Google Scholar
• ZongY, ZhangB, GuSet al.Structural basis of agrin-LRP4-MuSK signaling. Genes Dev.26(3), 247–258 (2012).
   PubMed Web of Science ®Google Scholar
• BoidoM, DeAmicis E, ValsecchiVet al.Increasing agrin function antagonizes muscle atrophy and motor impairment in spinal muscular atrophy. Front. Cell Neurosci.12, 17 (2018).
   PubMed Web of Science ®Google Scholar
• GlassDJ, BowenDC, StittTNet al.Agrin acts via a MuSK receptor complex. Cell85(4), 513–523 (1996).
   PubMed Web of Science ®Google Scholar
• BurdenS, VanDer Maarel S. An agonist antibody to MuSK as a theraputic for MuSK myasthenia gravis. http://grantome.com/grant/NIH/R21-NS088723-01A1
   Google Scholar
• HuijbersMG, VergoossenDL, Fillié-GrijpmaYEet al.MuSK myasthenia gravis monoclonal antibodies valency dictates pathogenicity. Neurol. Neuroimmunol. Neuroinflamm.6(3), e547 (2019).
   PubMed Web of Science ®Google Scholar
• Pérez-GarcíaMJ, BurdenSJ. Increasing MuSK activity delays denervation and improves motor function in ALS mice. Cell. Rep.2(3), 497–502 (2012).
   PubMed Web of Science ®Google Scholar
• Sengupta-GhoshA, DominguezSL, XieLet al.Muscle specific kinase (MuSK) activation preserves neuromuscular junctions in the diaphragm but is not sufficient to provide a functional benefit in the SOD1G93A mouse model of ALS. Neurobiol. Dis.124, 340–352 (2019).
   PubMed Web of Science ®Google Scholar
• ShafeyD, CôtéPD, KotharyR. Hypomorphic Smn knockdown C2C12 myoblasts reveal intrinsic defects in myoblast fusion and myotube morphology. Exp. Cell Res.311(1), 49–61 (2005).
   PubMed Web of Science ®Google Scholar
• BoyerJG, MurrayLM, ScottK, DeRepentigny Y, RenaudJ-M, KotharyR. Early onset muscle weakness and disruption of muscle proteins in mouse models of spinal muscular atrophy. Skelet. Muscle3(1), 24 (2013).
   PubMedGoogle Scholar
• BriccenoKV, MartinezT, LeikinaEet al.Survival motor neuron protein deficiency impairs myotube formation by altering myogenic gene expression and focal adhesion dynamics. Hum. Mol. Genet.23(18), 4745–4757 (2014).
   PubMed Web of Science ®Google Scholar
• FayzullinaS, MartinLJ. Skeletal muscle DNA damage precedes spinal motor neuron DNA damage in a mouse model of Spinal Muscular Atrophy (SMA). PLoS ONE9(3), e93329 (2014).
   PubMed Web of Science ®Google Scholar
• YiuEM, KornbergAJ. Duchenne muscular dystrophy. J. Paediatrics Child Health51(8), 759–764 (2015).
   PubMed Web of Science ®Google Scholar
• FreyFJ. Kinetics and dynamics of prednisolone. Endocr. Rev.8(4), 453–473 (1987).
   PubMed Web of Science ®Google Scholar
• BeenakkerEAC, FockJM, Van TolMJet al.Intermittent prednisone therapy in Duchenne muscular dystrophy: a randomized controlled trial. Arch. Neurol.62(1), 128–132 (2005).
   PubMedGoogle Scholar
• KeelingRM, GolumbekPT, StreifEM, ConnollyAM. Weekly oral prednisolone improves survival and strength in male mdx mice. Muscle Nerve35(1), 43–48 (2007).
   PubMed Web of Science ®Google Scholar
• QuattrocelliM, BarefieldDY, WarnerJLet al.Intermittent glucocorticoid steroid dosing enhances muscle repair without eliciting muscle atrophy. J. Clin. Invest.127(6), 2418–2432 (2017).
   PubMed Web of Science ®Google Scholar
• GrayS, WangB, OrihuelaYet al.Regulation of gluconeogenesis by Krüppel-like factor 15. Cell. Metab.5(4), 305–312 (2007).
   PubMed Web of Science ®Google Scholar
• HaldarSM, JeyarajD, AnandPet al.Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation. Proc. Natl Acad. Sci. USA109(17), 6739–6744 (2012).
   PubMed Web of Science ®Google Scholar
• LiuY, DongW, ShaoJ, WangY, ZhouM, SunH. Branched-chain amino acid negatively regulates KLF15 expression via PI3K-AKT pathway. Front. Physiol.8, 853 (2017).
   PubMed Web of Science ®Google Scholar
• WalterLM, DeguiseM-O, MeijboomKEet al.Interventions targeting glucocorticoid-Krüppel-like factor 15-branched-chain amino acid signaling improve disease phenotypes in spinal muscular atrophy mice. EBioMedicine31, 226–242 (2018).
   PubMed Web of Science ®Google Scholar
• MartinezA, AlonsoM, CastroA, PérezC, MorenoFJ. First non-ATP competitive glycogen synthase kinase 3 beta (GSK-3beta) inhibitors: thiadiazolidinones (TDZD) as potential drugs for the treatment of Alzheimer's disease. J. Med. Chem.45(6), 1292–1299 (2002).
   PubMed Web of Science ®Google Scholar
• WoodgettJR. Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J.9(8), 2431–2438 (1990).
   PubMed Web of Science ®Google Scholar
• SutherlandC, LeightonIA, CohenP. Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase connections in insulin and growth-factor signalling. Biochem. J.296(Pt 1), 15–19 (1993).
   PubMed Web of Science ®Google Scholar
• OchalekA, MihalikB, AvciHXet al.Neurons derived from sporadic Alzheimer's disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation. Alzheimers Res. Ther.9(1), 90 (2017).
   PubMed Web of Science ®Google Scholar
• LovestoneS, BoadaM, DuboisBet al.A Phase II trial of tideglusib in Alzheimer's disease. J. Alzheimers Dis.45(1), 75–88 (2015).
   PubMed Web of Science ®Google Scholar
• VerheesKJP, ScholsAMWJ, KeldersMCJM, Opden Kamp CMH, vander Velden JLJ, LangenRCJ. Glycogen synthase kinase-3β is required for the induction of skeletal muscle atrophy. Am. J. Physiol. Cell Physiol.301(5), C995–C1007 (2011).
   PubMed Web of Science ®Google Scholar
• vander Velden JLJ, LangenRCJ, KeldersMCJM, WoutersEFM, Janssen-HeiningerYMW, ScholsAMWJ. Inhibition of glycogen synthase kinase-3beta activity is sufficient to stimulate myogenic differentiation. Am. J. Physiol. Cell Physiol.290(2), C453–C462 (2006).
   PubMed Web of Science ®Google Scholar
• vander Velden JLJ, LangenRCJ, KeldersMCJMet al.Myogenic differentiation during regrowth of atrophied skeletal muscle is associated with inactivation of GSK-3beta. Am. J. Physiol. Cell Physiol.292(5), C1636–C1644 (2007).
   PubMed Web of Science ®Google Scholar
• ThorntonCA. Myotonic dystrophy. Neurol. Clin.32(3), 705–719 (2014).
   PubMed Web of Science ®Google Scholar
• HorriganJ, McMornA, SnapeM, NikolenkoN, GomesT, LochmullerH. AMO-02 (tideglusib) for the treatment of congenital and childhood onset myotonic dystrophy type 1. Neuromuscul. Disord.28, S14 (2018).
   Web of Science ®Google Scholar
• MakhortovaNR, HayhurstM, CerqueiraAet al.A screen for regulators of survival of motor neuron protein levels. Nat. Chem. Biol.7(8), 544–552 (2011).
   PubMed Web of Science ®Google Scholar
• RegadT. Targeting RTK signaling pathways in cancer. Cancers (Basel)7(3), 1758–1784 (2015).
   PubMed Web of Science ®Google Scholar
• FinkelRS, CrawfordTO, SwobodaKJet al.Candidate proteins, metabolites and transcripts in the biomarkers for spinal muscular atrophy (BforSMA) clinical study. PLoS ONE7(4), e35462 (2012).
   PubMed Web of Science ®Google Scholar
• ŠoltićD, BowermanM, StockJ, ShorrockHK, GillingwaterTH, FullerHR. Multi-study proteomic and bioinformatic identification of molecular overlap between amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Brain Sci.8(12), (2018).
   PubMed Web of Science ®Google Scholar
• FullerHR, GillingwaterTH, WishartTM. Commonality amid diversity: multi-study proteomic identification of conserved disease mechanisms in spinal muscular atrophy. Neuromuscul. Disord.26(9), 560–569 (2016).
   PubMed Web of Science ®Google Scholar