Efficacy of oligodendrocyte precursor cells as delivery vehicles for single-chain variable fragment to misfolded SOD1 in ALS rat model

1. Rosen, D.R., Siddique, T., Patterson, D., Figlewicz, D.A., Sapp, P., Hentati, A.,

Donaldson, D., Goto, J., O’Regan, J.P., Deng, H.X., et al. (1993). Mutations in Cu/

Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59–62.

17. Shodai, A., Ido, A., Fujiwara, N., Ayaki, T., Morimura, T., Oono, M., Uchida, T.,

Takahashi, R., Ito, H., and Urushitani, M. (2012). Conserved acidic amino acid residues in a second RNA recognition motif regulate assembly and function of TDP43. PLoS One 7, e52776.

2. Pramatarova, A., Figlewicz, D.A., Krizus, A., Han, F.Y., Ceballos-Picot, I., Nicole, A.,

Dib, M., Meininger, V., Brown, R.H., and Rouleau, G.A. (1995). Identification of new

mutations in the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosis. Am. J. Hum. Genet. 56, 592–596.

18. Takeuchi, S., Fujiwara, N., Ido, A., Oono, M., Takeuchi, Y., Tateno, M., Suzuki, K.,

Takahashi, R., Tooyama, I., Taniguchi, N., et al. (2010). Induction of protective immunity by vaccination with wild-type apo superoxide dismutase 1 in mutant SOD1

transgenic mice. J. Neuropathol. Exp. Neurol. 69, 1044–1056.

Molecular Therapy: Methods & Clinical Development Vol. 28 March 2023

327

Molecular Therapy: Methods & Clinical Development

19. Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng,

E.C., and Ferrin, T.E. (2004). UCSF Chimera–a visualization system for exploratory

research and analysis. J. Comput. Chem. 25, 1605–1612.

20. Nagai, M., Aoki, M., Miyoshi, I., Kato, M., Pasinelli, P., Kasai, N., Brown, R.H., Jr., and

Itoyama, Y. (2001). Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron disease. J. Neurosci. 21, 9246–9254.

21. Matsumoto, A., Okada, Y., Nakamichi, M., Nakamura, M., Toyama, Y., Sobue,

G., Nagai, M., Aoki, M., Itoyama, Y., and Okano, H. (2006). Disease progression

of human SOD1 (G93A) transgenic ALS model rats. J. Neurosci. Res. 83,

119–133.

22. Amado, D.A., and Davidson, B.L. (2021). Gene therapy for ALS: a review. Mol. Ther.

29, 3345–3358.

23. Tamaki, Y., Shodai, A., Morimura, T., Hikiami, R., Minamiyama, S., Ayaki, T.,

Tooyama, I., Furukawa, Y., Takahashi, R., and Urushitani, M. (2018). Elimination

of TDP-43 inclusions linked to amyotrophic lateral sclerosis by a misfolding-specific

intrabody with dual proteolytic signals. Sci. Rep. 8, 6030.

24. Ishigaki, A., Aoki, M., Nagai, M., Warita, H., Kato, S., Kato, M., Nakamura, T.,

Funakoshi, H., and Itoyama, Y. (2007). Intrathecal delivery of hepatocyte growth

factor from amyotrophic lateral sclerosis onset suppresses disease progression in

rat amyotrophic lateral sclerosis model. J. Neuropathol. Exp. Neurol. 66,

1037–1044.

25. Komatsu, Y., Tanaka, C., Komorizono, R., and Tomonaga, K. (2020). In vivo biodistribution analysis of transmission competent and defective RNA virus-based

episomal vector. Sci. Rep. 10, 5890.

36. Liu, H.N., Tjostheim, S., Dasilva, K., Taylor, D., Zhao, B., Rakhit, R., Brown, M.,

Chakrabartty, A., McLaurin, J., and Robertson, J. (2012). Targeting of monomer/misfolded SOD1 as a therapeutic strategy for amyotrophic lateral sclerosis. J. Neurosci.

32, 8791–8799.

37. Dong, Q.X., Zhu, J., Liu, S.Y., Yu, X.L., and Liu, R.T. (2018). An oligomer-specific antibody improved motor function and attenuated neuropathology in the

SOD1-G93A transgenic mouse model of ALS. Int. Immunopharmacol. 65,

413–421.

38. Fujisawa, T., Homma, K., Yamaguchi, N., Kadowaki, H., Tsuburaya, N., Naguro, I.,

Matsuzawa, A., Takeda, K., Takahashi, Y., Goto, J., et al. (2012). A novel monoclonal

antibody reveals a conformational alteration shared by amyotrophic lateral sclerosislinked SOD1 mutants. Ann. Neurol. 72, 739–749.

39. Harrington, E.P., Bergles, D.E., and Calabresi, P.A. (2020). Immune cell modulation

of oligodendrocyte lineage cells. Neurosci. Lett. 715, 134601.

40. Pirillo, A., Norata, G.D., and Catapano, A.L. (2013). LOX-1, OxLDL, and atherosclerosis. Mediat. Inflamm. 2013, 152786.

41. Nardo, G., Iennaco, R., Fusi, N., Heath, P.R., Marino, M., Trolese, M.C., Ferraiuolo, L.,

Lawrence, N., Shaw, P.J., and Bendotti, C. (2013). Transcriptomic indices of fast and

slow disease progression in two mouse models of amyotrophic lateral sclerosis. Brain

136, 3305–3332.

42. Nardo, G., Trolese, M.C., de Vito, G., Cecchi, R., Riva, N., Dina, G., Heath, P.R.,

Quattrini, A., Shaw, P.J., Piazza, V., and Bendotti, C. (2016). Immune response in peripheral axons delays disease progression in SOD1G93A mice. J. Neuroinflammation

13, 261.

26. Hans, A., Bajramovic, J.J., Syan, S., Perret, E., Dunia, I., Brahic, M., and GonzalezDunia, D. (2004). Persistent, noncytolytic infection of neurons by Borna disease virus

interferes with ERK 1/2 signaling and abrogates BDNF-induced synaptogenesis.

Faseb. J. 18, 863–865.

43. Akamatsu, T., Sugiyama, T., Oshima, T., Aoki, Y., Mizukami, A., Goishi, K.,

Shichino, H., Kato, N., Takahashi, N., Goto, Y.I., et al. (2021). Lectin-like oxidized

low-density lipoprotein Receptor-1-Related microglial activation in neonatal hypoxic-ischemic encephalopathy: morphologic consideration. Am. J. Pathol. 191,

1303–1313.

27. Fu, H., Hu, D., Zhang, L., Shen, X., and Tang, P. (2018). Efficacy of oligodendrocyte progenitor cell transplantation in rat models with traumatic thoracic spinal

cord injury: a systematic review and meta-analysis. J. Neurotrauma 35,

2507–2518.

44. Garofalo, S., Cocozza, G., Porzia, A., Inghilleri, M., Raspa, M., Scavizzi, F., Aronica, E.,

Bernardini, G., Peng, L., Ransohoff, R.M., et al. (2020). Natural killer cells modulate

motor neuron-immune cell cross talk in models of amyotrophic lateral sclerosis. Nat.

Commun. 11, 1773.

28. Yamanaka, K., Boillee, S., Roberts, E.A., Garcia, M.L., McAlonis-Downes, M., Mikse,

O.R., Cleveland, D.W., and Goldstein, L.S.B. (2008). Mutant SOD1 in cell types other

than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice.

Proc. Natl. Acad. Sci. USA 105, 7594–7599.

45. Swarup, V., Phaneuf, D., Dupré, N., Petri, S., Strong, M., Kriz, J., and Julien, J.P.

(2011). Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor kB-mediated pathogenic pathways. J. Exp. Med. 208, 2429–2447.

29. Ng Kee Kwong, K.C., Gregory, J.M., Pal, S., Chandran, S., and Mehta, A.R. (2020).

Cerebrospinal fluid cytotoxicity in amyotrophic lateral sclerosis: a systematic review

of in vitro studies. Brain Commun. 2, fcaa121.

46. Kumar, S., Phaneuf, D., and Julien, J.P. (2021). Withaferin-A treatment alleviates

TAR DNA-binding Protein-43 pathology and improves cognitive function in a

mouse model of FTLD. Neurotherapeutics 18, 286–296.

30. Tokuda, E., Takei, Y.I., Ohara, S., Fujiwara, N., Hozumi, I., and Furukawa, Y. (2019).

Wild-type Cu/Zn-superoxide dismutase is misfolded in cerebrospinal fluid of sporadic amyotrophic lateral sclerosis. Mol. Neurodegener. 14, 42.

47. Nakamura, R., Kurihara, M., Ogawa, N., Kitamura, A., Yamakawa, I., Bamba, S.,

Sanada, M., Sasaki, M., and Urushitani, M. (2021). Prognostic prediction by hypermetabolism varies depending on the nutritional status in early amyotrophic lateral

sclerosis. Sci. Rep. 11, 17943.

31. Eykens, C., Rossaert, E., Duqué, S., Rué, L., Bento-Abreu, A., Hersmus, N., Lenaerts,

A., Kerstens, A., Corthout, N., Munck, S., et al. (2021). AAV9-mediated gene delivery

of MCT1 to oligodendrocytes does not provide a therapeutic benefit in a mouse

model of ALS. Mol. Ther. Methods Clin. Dev. 20, 508–519.

48. Nakamura, R., Kurihara, M., Ogawa, N., Kitamura, A., Yamakawa, I., Bamba, S.,

Sanada, M., Sasaki, M., and Urushitani, M. (2022). Investigation of the prognostic

predictive value of serum lipid profiles in amyotrophic lateral sclerosis: roles of sex

and hypermetabolism. Sci. Rep. 12, 1826.

32. Hayashi, Y., Homma, K., and Ichijo, H. (2016). SOD1 in neurotoxicity and its controversial roles in SOD1 mutation-negative ALS. Adv. Biol. Regul. 60, 95–104.

49. Ingre, C., Chen, L., Zhan, Y., Termorshuizen, J., Yin, L., and Fang, F. (2020). Lipids,

apolipoproteins, and prognosis of amyotrophic lateral sclerosis. Neurology 94,

e1835–e1844.

33. Meininger, V., Genge, A., van den Berg, L.H., Robberecht, W., Ludolph, A., Chio, A.,

Kim, S.H., Leigh, P.N., Kiernan, M.C., Shefner, J.M., et al.; NOG112264 Study Group

(2017). Safety and efficacy of ozanezumab in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol.

16, 208–216.

50. Guttenplan, K.A., Weigel, M.K., Prakash, P., Wijewardhane, P.R., Hasel, P., RufenBlanchette, U., Münch, A.E., Blum, J.A., Fine, J., Neal, M.C., et al. (2021).

Neurotoxic reactive astrocytes induce cell death via saturated lipids. Nature 599,

102–107.

34. Brotherton, T.E., Li, Y., Cooper, D., Gearing, M., Julien, J.P., Rothstein, J.D., Boylan,

K., and Glass, J.D. (2012). Localization of a toxic form of superoxide dismutase 1 protein to pathologically affected tissues in familial ALS. Proc. Natl. Acad. Sci. USA 109,

5505–5510.

35. Maier, M., Welt, T., Wirth, F., Montrasio, F., Preisig, D., McAfoose, J., Vieira, F.G.,

Kulic, L., Späni, C., Stehle, T., et al. (2018). A human-derived antibody targets misfolded SOD1 and ameliorates motor symptoms in mouse models of amyotrophic

lateral sclerosis. Sci. Transl. Med. 10, eaah3924.

328

51. Kong, Y., Wu, J.B., Wang, X., Zhao, J.F., Song, H., and Yuan, L.D. (2014).

Polymorphism of the OLR1 30 UTR potential microRNA binding site and risk of

Alzheimer’s disease: a meta-analysis. Genet. Mol. Res. 13, 10162–10172.

52. Urushitani, M., Kurisu, J., Tsukita, K., and Takahashi, R. (2002). Proteasomal inhibition by misfolded mutant superoxide dismutase 1 induces selective motor neuron

death in familial amyotrophic lateral sclerosis. J. Neurochem. 83, 1030–1042.

53. Schneider, C.A., Rasband, W.S., and Eliceiri, K.W. (2012). NIH Image to ImageJ: 25

years of image analysis. Nat. Methods 9, 671–675.

Molecular Therapy: Methods & Clinical Development Vol. 28 March 2023

www.moleculartherapy.org

54. Maki, T., Takahashi, Y., Miyamoto, N., Liang, A.C., Ihara, M., Lo, E.H., and Arai, K.

(2015). Adrenomedullin promotes differentiation of oligodendrocyte precursor cells

into myelin-basic-protein expressing oligodendrocytes under pathological conditions

in vitro. Stem Cell Res. 15, 68–74.

55. Yasuda, K., Maki, T., Kinoshita, H., Kaji, S., Toyokawa, M., Nishigori, R., Kinoshita,

Y., Ono, Y., Kinoshita, A., and Takahashi, R. (2020). Sex-specific differences in tran-

scriptomic profiles and cellular characteristics of oligodendrocyte precursor cells.

Stem Cell Res. 46, 101866. https://doi.org/10.1016/j.scr.2020.101866.

56. Ono, Y., Maejima, Y., Saito, M., Sakamoto, K., Horita, S., Shimomura, K., Inoue, S.,

and Kotani, J. (2020). TAK-242, a specific inhibitor of Toll-like receptor 4 signalling,

prevents endotoxemia-induced skeletal muscle wasting in mice. Sci. Rep. 10, 694.

https://doi.org/10.1038/s41598-020-57714-3.

Molecular Therapy: Methods & Clinical Development Vol. 28 March 2023

329

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