Abstract
Background
Spinal Muscular Atrophy (SMA) is a genetic disorder resulting from deficiency of the survival motor neuron (SMN) protein. Emerging evidence indicates that SMA is associated with disruptions in neuroactive amino acid metabolism, contributing to altered neurotransmission. Taurine, the predominant inhibitory neuromodulator in the developing central nervous system (CNS), is critical for synaptic function, osmoregulation, and neuroprotection. Despite its physiological significance, the effects of SMN deficiency on taurine homeostasis and its potential role in SMA pathophysiology remain unexplored.
Methods
We used high-performance liquid chromatography (HPLC) to quantify taurine in the spinal cord, brainstem, cortex, and cerebellum in SMN∆7 mice, during postnatal development. We then translate our observation into the clinic by measuring taurine concentrations in the cerebrospinal fluid (CSF) from control individuals (n = 7) and SMA patients of varying disease severity (n = 37) before and after therapy with the SMN-inducing drug Nusinersen.
Results
Our data show a downregulation of taurine levels in the brainstem of SMN∆7 mice at late symptomatic stage relative to control littermates. Furthermore, we highlight a taurine reduction in the CSF of naïve SMA1 patients compared to controls. Importantly, Nusinersen treatment restored the taurine deficit in these SMA patients.
Conclusions
These findings demonstrate that SMN deficiency dysregulates taurine homeostasis in the CNS of overt symptomatic mouse models and SMA1 patients. They also reveal the therapeutic efficacy of Nusinersen treatment in correcting this amino acid deficit. However, further research is needed to determine the mechanisms by which SMN deficiency causes taurine dysregulation and its potential contribution to SMA pathology.
Plain language summary
Spinal Muscular Atrophy (SMA) is a genetic condition that can be life threatening in infants. Research shows that SMA may change the way the body handles certain natural chemicals that help the brain work properly. One of these chemicals is taurine, which plays an important role in calming and guiding brain activity as babies develop. Until now, taurine had not been studied in connection with SMA. In our study, we found that taurine levels were lower both in mice with SMA and in children with the most severe form of the condition (type 1). Importantly, when these children were treated with the medicine Nusinersen, their taurine levels returned to normal. This suggests that taurine could be closely linked to how SMA develops and affects the brain.
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Data availability
Source data for Figures and Tables included in this manuscript can be accessed from Supplementary Data 1.
References
Lefebvre, S. et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80, 155–165 (1995).
Tisdale, S. & Pellizzoni, L. Disease mechanisms and therapeutic approaches in spinal muscular atrophy. J. Neurosci. Off. J. Soc. Neurosci. 35, 8691–8700 (2015).
Lorson, C. L., Hahnen, E., Androphy, E. J. & Wirth, B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc. Natl. Acad. Sci. USA. 96, 6307–6311 (1999).
Monani, U. R. et al. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum. Mol. Genet. 8, 1177–1183 (1999).
Wirth, B. Spinal muscular atrophy: in the challenge lies a solution. Trends Neurosci 44, 306–322 (2021).
Lunn, M. R. & Wang, C. H. Spinal muscular atrophy. The Lancet 371, 2120–2133 (2008).
Chaytow, H., Faller, K. M. E., Huang, Y.-T. & Gillingwater, T. H. Spinal muscular atrophy: from approved therapies to future therapeutic targets for personalized medicine. Cell Rep. Med. 2, 100346 (2021).
Schroth, M. K. et al. Spinal muscular atrophy update in best practices: recommendations for treatment considerations. Neurol. Clin. Pract. 15, e200374 (2025).
Menduti, G., Rasà, D. M., Stanga, S. & Boido, M. Drug screening and drug repositioning as promising therapeutic approaches for spinal muscular atrophy treatment. Front. Pharmacol. 11, 592234 (2020).
Fletcher, E. V. et al. Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in spinal muscular atrophy. Nat. Neurosci. 20, 905–916 (2017).
Mentis, G. Z. et al. Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy. Neuron 69, 453–467 (2011).
Ling, K. K. Y., Lin, M.-Y., Zingg, B., Feng, Z. & Ko, C.-P. Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy. PloS One 5, e15457 (2010).
Simon, C. M. et al. Stasimon contributes to the loss of sensory synapses and motor neuron death in a mouse model of spinal muscular atrophy. Cell Rep 29, 3885–3901.e5 (2019).
Buettner, J. M. et al. Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models. iScience 24, 103376 (2021).
Sun, J. & Harrington, M. A. The alteration of intrinsic excitability and synaptic transmission in lumbar spinal motor neurons and interneurons of severe spinal muscular atrophy mice. Front. Cell. Neurosci. 13, 15 (2019).
James, R., Chaytow, H., Ledahawsky, L. M. & Gillingwater, T. H. Revisiting the role of mitochondria in spinal muscular atrophy. Cell. Mol. Life Sci. 78, 4785–4804 (2021).
Errico, F. et al. Nusinersen induces disease-severity-specific neurometabolic effects in spinal muscular atrophy. Biomolecules 12, 1431 (2022).
Faravelli, I. et al. Multi-omics profiling of CSF from spinal muscular atrophy type 3 patients after nusinersen treatment: a 2-year follow-up multicenter retrospective study. Cell. Mol. Life Sci. CMLS 80, 241 (2023).
Hassan, A. et al. Dysregulated balance of D- and L-amino acids modulating glutamatergic neurotransmission in severe spinal muscular atrophy. Neurobiol. Dis. 207, 106849 (2025).
Lu, M. et al. Metabolomics of cerebrospinal fluid reveals candidate diagnostic biomarkers to distinguish between spinal muscular atrophy type II and type III. CNS Neurosci. Ther. 30, e14718 (2024).
Valsecchi, V. et al. SMN deficiency perturbs monoamine neurotransmitter metabolism in spinal muscular atrophy. Commun. Biol. 6, 1155 (2023).
Zandl-Lang, M. et al. Multi-omics profiling in spinal muscular atrophy (SMA): investigating lipid and metabolic alterations through longitudinal CSF analysis of Nusinersen-treated patients. J. Neurol. 272, 183 (2025).
Zhuang, W. et al. Dysregulation of cerebrospinal fluid metabolism profiles in spinal muscular atrophy patients: a case control study. Ital. J. Pediatr. 50, 154 (2024).
Collier, J. J., Oláhová, M., McWilliams, T. G. & Taylor, R. W. Mitochondrial signalling and homeostasis: from cell biology to neurological disease. Trends Neurosci 46, 137–152 (2023).
Wu, J.-Y. & Prentice, H. Role of taurine in the central nervous system. J. Biomed. Sci. 17, S1 (2010).
Schaffer, S. & Kim, H. W. Effects and mechanisms of taurine as a therapeutic agent. Biomol. Ther. 26, 225–241 (2018).
El Idrissi, A. & Trenkner, E. Taurine as a modulator of excitatory and inhibitory neurotransmission. Neurochem. Res. 29, 189–197 (2004).
Hayashi, M. et al. Oxidative stress and disturbed glutamate transport in spinal muscular atrophy. Brain Dev 24, 770–775 (2002).
Miller, N., Shi, H., Zelikovich, A. S. & Ma, Y.-C. Motor neuron mitochondrial dysfunction in spinal muscular atrophy. Hum. Mol. Genet. 25, 3395–3406 (2016).
Chen, W. Q. et al. Role of taurine in regulation of intracellular calcium level and neuroprotective function in cultured neurons. J. Neurosci. Res. 66, 612–619 (2001).
Kilb, W. & Fukuda, A. Taurine as an Essential Neuromodulator during Perinatal Cortical Development. Front. Cell. Neurosci. 11, 103376 (2017).
Kuriyama, K. & Hashimoto, T. Interrelationship between taurine and GABA. Adv. Exp. Med. Biol. 442, 329–337 (1998).
Roysommuti, S. & Wyss, J. M. The effects of taurine exposure on the brain and neurological disorders. in Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease 207–213 https://doi.org/10.1016/B978-0-12-411462-3.00022-9 (Elsevier, 2015).
Brand, A., Leibfritz, D., Hamprecht, B. & Dringen, R. Metabolism of cysteine in astroglial cells: synthesis of hypotaurine and taurine. J. Neurochem. 71, 827–832 (1998).
El Idrissi, A. & Trenkner, E. Taurine regulates mitochondrial calcium homeostasis. Adv. Exp. Med. Biol. 526, 527–536 (2003).
Griffiths, E. J. & Rutter, G. A. Mitochondrial calcium as a key regulator of mitochondrial ATP production in mammalian cells. Biochim. Biophys. Acta 1787, 1324–1333 (2009).
Izquierdo, J. M. Taurine as a possible therapy for immunosenescence and inflammaging. Cell. Mol. Immunol. 21, 3–5 (2024).
Jong, C. J., Sandal, P. & Schaffer, S. W. The role of taurine in mitochondria health: more than just an antioxidant. Molecules 26, 4913 (2021).
Boido, M. et al. Agonist of growth hormone-releasing hormone improves the disease features of spinal muscular atrophy mice. Proc. Natl. Acad. Sci. USA. 120, e2216814120 (2023).
Coratti, G. et al. Motor function in type 2 and 3 SMA patients treated with Nusinersen: a critical review and meta-analysis. Orphanet J. Rare Dis. 16, 430 (2021).
Pane, M. et al. Nusinersen in type 1 spinal muscular atrophy: Twelve-month real-world data. Ann. Neurol. 86, 443–451 (2019).
Pane, M. et al. An observational study of functional abilities in infants, children, and adults with type 1 SMA. Neurology 91, e696–e703 (2018).
Hassan, A. et al. Nusinersen corrects L-arginine deficiency in the cerebrospinal fluid of patients with severe spinal muscular atrophy. Neurobiol. Dis. 214, 107046 (2025).
Kuriyama, K., Ohkuma, S., Kishi, M. & Kimori, M. Development of Biosynthesizing and Uptake Systems for Taurine in Cerebral Cortical Neurons in Primary Culture: Analysis of Possible Factors Involved in Perinatal Decline of Cerebral Taurine. in The Biology of Taurine: Methods and Mechanisms (eds. Huxtable, R. J., Franconi, F. & Giotti, A.) 69–77 https://doi.org/10.1007/978-1-4899-0405-8_7 (Springer US, Boston, MA, 1987).
Rafiee, Z., García-Serrano, A. M. & Duarte, J. M. N. Taurine supplementation as a neuroprotective strategy upon brain dysfunction in metabolic syndrome and diabetes. Nutrients 14, 1292 (2022).
Murray, L. M. et al. Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy. Hum. Mol. Genet. 17, 949–962 (2008).
Woschitz, V., Mei, I., Hedlund, E. & Murray, L. M. Mouse models of SMA show divergent patterns of neuronal vulnerability and resilience. Skelet. Muscle 12, 22 (2022).
Zhang, Z. et al. Dysregulation of synaptogenesis genes antecedes motor neuron pathology in spinal muscular atrophy. Proc. Natl. Acad. Sci. USA 110, 19348–19353 (2013).
Vitvitsky, V., Garg, S. K. & Banerjee, R. Taurine biosynthesis by neurons and astrocytes. J. Biol. Chem. 286, 32002–32010 (2011).
Ohuchi, K. et al. Notch signaling mediates astrocyte abnormality in spinal muscular atrophy model systems. Sci. Rep. 9, 3701 (2019).
Rindt, H. et al. Astrocytes influence the severity of spinal muscular atrophy. Hum. Mol. Genet. 24, 4094–4102 (2015).
Schmitt, L.-I. et al. Spinal astrocyte dysfunction drives motor neuron loss in late-onset spinal muscular atrophy. Acta Neuropathol. (Berl.) 145, 611–635 (2023).
Saransaari, P. & Oja, S. S. Nitric oxide is involved in taurine release in the mouse brain stem under normal and ischemic conditions. Amino Acids 34, 429–436 (2008).
Saransaari, P. & Oja, S. S. Ischemia-induced taurine release is modified by nitric oxide-generating compounds in slices from the developing and adult mouse hippocampus. Neurochem. Res. 27, 395–402 (2002).
Saransaari, P. & Oja, S. S. Taurine release modified by nitric oxide-generating compounds in the developing and adult mouse hippocampus. Neuroscience 89, 1103–1111 (1999).
Simon, C. M. et al. A stem cell model of the motor circuit uncouples motor neuron death from hyperexcitability induced by SMN deficiency. Cell Rep. 16, 1416–1430 (2016).
Elhussiny, M. Z. et al. Intracerebroventricular injection of taurine induces hypothermia through modifying monoaminergic pathways in chicks. Eur. J. Pharmacol. 928, 175092 (2022).
Kontro, P., Korpi, E. R., Oja, O. S. & Oja, S. S. Modulation of noradrenaline uptake and release by taurine in rat cerebral slices. Neuroscience 13, 663–666 (1984).
Pagiazitis, J. G. et al. Catecholaminergic dysfunction drives postural and locomotor deficits in a mouse model of spinal muscular atrophy. Cell Rep 44, 115147 (2025).
Nakazato, T. et al. Plasma taurine is an axonal excitability-translatable biomarker for amyotrophic lateral sclerosis. Sci. Rep. 12, 9155 (2022).
Purves, D. et al. Lower Motor Neuron Circuits and Motor Control. in Neuroscience 6th edn (Sinauer Associates, 2018).
Coelho-Santos, V. & Shih, A. Y. Postnatal development of cerebrovascular structure and the neurogliovascular unit. Wiley Interdiscip. Rev. Dev. Biol. 9, e363 (2020).
Ommati, M. M. et al. Pre/postnatal taurine supplementation improves neurodevelopment and brain function in mice offspring: a persistent developmental study from puberty to maturity. Life Sci 336, 122284 (2024).
Rassin, D. K., Sturman, J. A. & Gaull, G. E. Taurine and other free amino acids in milk of man and other mammals. Early Hum. Dev. 2, 1–13 (1978).
Semple, B. D., Blomgren, K., Gimlin, K., Ferriero, D. M. & Noble-Haeusslein, L. J. Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species. Prog. Neurobiol. 106, 1–16 (2013).
Kubo, T., Amano, M., Ishizuka, T. & Ozaki, S. beta-Alanine and taurine microinjected into the rat caudal ventrolateral medulla increase blood pressure. Clin. Exp. Hypertens. N. Y. N 1993 15, 585–597 (1993).
Meeley, M. P., Underwood, M. D., Talman, W. T. & Reis, D. J. Content and in vitro release of endogenous amino acids in the area of the nucleus of the solitary tract of the rat. J. Neurochem. 53, 1807–1817 (1989).
Saransaari, P. & Oja, S. S. Taurine release in mouse brain stem slices under cell-damaging conditions. Amino Acids 32, 439–446 (2007).
Wang, J., Peng, Y.-J. & Zhu, D.-N. Amino acids modulate the hypotensive effect of angiotensin-(1-7) at the caudal ventrolateral medulla in rats. Regul. Pept. 129, 1–7 (2005).
Heier, C. R., Satta, R., Lutz, C. & DiDonato, C. J. Arrhythmia and cardiac defects are a feature of spinal muscular atrophy model mice. Hum. Mol. Genet. 19, 3906–3918 (2010).
Walter, L. M. et al. Interventions targeting glucocorticoid-Krüppel-like factor 15-branched-chain amino acid signaling improve disease phenotypes in spinal muscular atrophy mice. EBioMedicine 31, 226–242 (2018).
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on the substantiation of health claims related to taurine and “immune system protection” (ID 611), “metabolism processes” (ID 613), contribution to normal cognitive function (ID 1659), maintenance of normal cardiac function (ID 1661), maintenance of normal muscle function (ID 1949) and delay in the onset of physical fatigue during exercise (ID 1958) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J. 9, 2035 (2011).
Acknowledgements
A.U., T.N., R.d.V., E.B., and A.D.A. were supported by #NEXTGENERATIONEU (NGEU) funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006) – A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022). E.B. and A.D.A. were also supported by a grant from Ricerca Finalizzata from the Italian Ministry of Health (Project nr RF-2019-12370334); C.B. and F.E. were supported by Ministry of Health, NextGenerationEU (Project PNRR-POC-2023-12377653). E.B., A.D., C.P., and C.B. are members of the ERN NMD European Network (Project nr 2016/557). L.P. was supported by NIH grants R01NS102451, R01NS114218, and R01NS116400. This work was also supported by Department of Excellence funding from the Ministry of University and Research (MUR) for 2023-2027, awarded to the Department of Neuroscience “Rita Levi Montalcini” (University of Turin), and by the Girotondo/ONLUS and SMArathonONLUS foundations”, granted to A.V. and M.B.
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A.U. conceived and designed the study; R.d.V. and A.H. performed the HPLC experiments and analysed the results; R.d.V. and T.N. performed the statistical analysis; R.d.V. prepared figures and wrote the manuscript; A.D.A., C.P., C.B., E.B. performed clinical evaluations and provided CSF samples; A.C., M.B., and A.V. worked with SMNΔ7 mouse colony and provided tissue samples; L.P. provided advice and contributed to manuscript writing. A.U. and F.E. supervised the project. All authors read and edited the paper and agree with the final version of the manuscript.
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E.B. received advisory board honoraria from Roche, Biogen, PTC, Red Nucleus. None of these founders had a role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. The other authors declare no competing interests.
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di Vito, R., Hassan, A., Nuzzo, T. et al. Nusinersen rescues taurine deficiency in patients with type 1 Spinal Muscular Atrophy. Commun Med (2026). https://doi.org/10.1038/s43856-026-01434-8
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DOI: https://doi.org/10.1038/s43856-026-01434-8
