[Dimebon delays the onset of symptoms of FUS-proteinopathy in transgenic mice].

AIM To evaluate an effect of dimebon on the onset of symptomatic stage in FUS.1-513 transgenic mice - a new genetic model of neurodegeneration, and to study the dynamics of disease progression in the terminal stage. MATERIAL AND METHODS The study was carried out on males of line FUS1-513 with the contribution of genes from CD1 strains. Mice of the experimental group (n=28) received dimebon with water in the concentration of 70 mcg/ml starting from the 35th day of life. The control group (n=25) did not receive the drug. Age, body mass of animals at the start of symptomatic stage and duration of symptomatic stage were assessed. RESULTS Application of dimebon can delay the onset of the manifestation of clinical symptoms of the neurodegenerative process in the experimental group (127.6±4.6 days) compared to the control group (110.6±4.2 days). The body mass was similar in both groups. CONCLUSION Dimebon leads to an increase in the duration of presymptomatic stage and delays the manifestation of clinical symptoms. The changes in the dynamics of the pathological process in the symptomatic stage are not detected.

[1]  Anthony R White,et al.  Advances in the Development of Disease-Modifying Treatments for Amyotrophic Lateral Sclerosis , 2016, CNS Drugs.

[2]  S. Illarioshkin,et al.  Genetic studies of Russian patients with amyotrophic lateral sclerosis , 2016, Amyotrophic lateral sclerosis & frontotemporal degeneration.

[3]  H. Mitsumoto,et al.  The Dilemma of the Clinical Trialist in Amyotrophic Lateral Sclerosis: The Hurdles to Finding a Cure. , 2015, Neurologic clinics.

[4]  V. Buchman,et al.  Gamma-carboline inhibits neurodegenerative processes in a transgenic model of amyotrophic lateral sclerosis , 2015, Doklady Biochemistry and Biophysics.

[5]  S. Bachurin,et al.  Novel Sites of Neuroprotective Action of Dimebon (Latrepirdine) , 2015, Molecular Neurobiology.

[6]  J. Hodges,et al.  FTD and ALS—translating mouse studies into clinical trials , 2015, Nature Reviews Neurology.

[7]  P. Visscher,et al.  Motor neuron disease: Common genetic variants and the heritability of ALS , 2014, Nature Reviews Neurology.

[8]  V. Buchman,et al.  Fused in Sarcoma (FUS) Protein Lacking Nuclear Localization Signal (NLS) and Major RNA Binding Motifs Triggers Proteinopathy and Severe Motor Phenotype in Transgenic Mice , 2013, The Journal of Biological Chemistry.

[9]  P. Tsvetkov,et al.  Proteinopathies, neurodegenerative disorders with protein aggregation-based pathology , 2012, Molecular Biology.

[10]  V. Buchman,et al.  Dimebon Reduces the Levels of Aggregated Amyloidogenic Protein Forms in Detergent-Insoluble Fractions In Vivo , 2012, Bulletin of Experimental Biology and Medicine.

[11]  L. Blackhall.  Amyotrophic lateral sclerosis and palliative care: Where we are, and the road ahead , 2012, Muscle & nerve.

[12]  V. Buchman,et al.  Dimebon Slows Progression of Proteinopathy in γ-Synuclein Transgenic Mice , 2011, Neurotoxicity Research.

[13]  A. Deykin,et al.  The state of health and the reproductive potential of transgenic mice secreting recombinant human lactoferrin in milk , 2009, Doklady Biochemistry and Biophysics.

[14]  M. Goedert,et al.  Methylene blue and dimebon inhibit aggregation of TDP‐43 in cellular models , 2009, FEBS letters.

[15]  A. P. Smirnov,et al.  [A mice model of amyotrophic lateral sclerosis expressing mutant human FUS protein]. , 2014, Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova.

[16]  V. Skvortsova,et al.  [Modeling of lateral amyotrophic sclerosis: a non-genetic method]. , 2013, Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova.