Effect of 3,4-diaminopyridine phosphate in symptomatic SOD1-G93A mice

Authors

  • Swathi Beladakere Ramaswamy MD University of Missouri
  • John A. Stanford PhD
  • Stanley Iyadurai MD PhD
  • Raghav Govindarajan MD
  • Richard J. Barohn MD

DOI:

https://doi.org/10.17161/rrnmf.v2i5.15641

Keywords:

SOD1-G93A, ALS, 3,4-DAPP

Abstract

Objective: To study the effect of 3,4-diaminopyridine phosphate (3,4-DAPP) on body weight, grip strength, neurological score and survival in symptomatic SOD1-G93A mice.

 

Method: We administered 3,4-diaminopyridine phosphate (3,4-DAPP) at 0, 8, and 16 mg/kg to SOD1-G93A mice 5 days/week beginning at 90 days of age. We measured body weight, grip strength, neurological score and survival in this model of ALS.

 

Results: 3,4-DAPP had no influence on body weight, grip strength, neurological score or survival in this transgenic mouse model.

 

Conclusion: Our study showed that 3,4-DAPP administration had no effects on survival, body weight, grip strength and neurological score of mice with SOD1 mutation. Since the results of this study are of limited significance, larger animal studies are required to investigate the utility of 3,4-DAPP.

Metrics

Metrics Loading ...

Downloads

Download data is not yet available.

References

Chand, K. K., Lee, K. M., Lee, J. D., Qiu, H., Willis, E. F., Lavidis, N. A., … Noakes, P. G. (2018). Defects in synaptic transmission at the neuromuscular junction precede motor deficits in a TDP-43Q331K transgenic mouse model of amyotrophic lateral sclerosis. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 32(5), 2676–2689.

Cappello, V., & Francolini, M. (2017). Neuromuscular junction dismantling in Amyotrophic Lateral Sclerosis. International Journal of Molecular Sciences, 18(10).

Thomsen RH, Wilson DF. Effects of 4-aminopyridine and 3,4-diaminopyridine on transmitter release at the neuromuscular junction. J. Pharmacol. Exp. Ther. 227, 260–265 (1983).

Kirsch GE, Narahashi T. 3,4-diaminopyridine. A potent new potassium channel blocker. Biophys. J. 22, 507–512 (1978).

Sanders DB. 3,4-Diaminopyridine (DAP) in the treatment of Lambert–Eaton myasthenic syndrome (LEMS). Ann. NY Acad. Sci. 841, 811–816 (1998)

Wu H., Xiong W.C., Mei L. To build a synapse: Signaling pathways in neuromuscular junction assembly. Development. 2010;137:1017–1033. doi: 10.1242/dev.038711.

Lin W., Burgess R.W., Dominguez B., Pfaff S.L., Sanes J.R., Lee K.F. Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. Nature. 2001;410:1057–1064.

Yang X., Arber S., William C., Li L., Tanabe Y., Jessell T.M., Birchmeier C., Burden S.J. Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation. Neuron. 2001;30:399–410.

Bastos A.F., Orsini M., Machado D., Mello M.P., Nader S., Silva J.G., da Silva Catharino A.M., de Freitas M.R., Pereira A., Pessoa L.L., et al. Amyotrophic lateral sclerosis: One or multiple causes? Neurol. Int. 2011;3:e4.

Cappello V., Vezzoli E., Righi M., Fossati M., Mariotti R., Crespi A., Patruno M., Bentivoglio M., Pietrini G., Francolini M. Analysis of neuromuscular junctions and effects of anabolic steroid administration in the SOD1G93A mouse model of ALS. Mol. Cell. Neurosci. 2012;51:12–21.

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. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362:59–62.

Turner B.J., Talbot K. Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS. Prog. Neurobiol. 2008;85:94–134.

Wirtz, P. W., Titulaer, M. J., Gerven, J. M. van, & Verschuuren, J. J. (2010). 3,4-diaminopyridine for the treatment of Lambert–Eaton myasthenic syndrome. Expert Review of Clinical Immunology, 6(6), 867–874.

Downloads

Published

2022-03-11

Issue

Section

New Discoveries/New Stuff (Original Research)

How to Cite

Beladakere Ramaswamy, S., Stanford, J. A. ., Iyadurai, S. ., Govindarajan, R., & Barohn, R. (2022). Effect of 3,4-diaminopyridine phosphate in symptomatic SOD1-G93A mice. RRNMF Neuromuscular Journal, 3(1), 31-33. https://doi.org/10.17161/rrnmf.v2i5.15641