Profile of pridopidine and its potential in the treatment of Huntington disease: The evidence to date

Drug Design, Development and Therapy

Volumn 9, Issue , 2015, Pages 5827-5833

  Squitieri, Ferdinando ^a   de Yebenes, Justo Garcia ^b  

^a CASA SOLLIEVO DELLA SOFFERENZA HOSPITAL   (Italy)

^b Estudio y Desarrollo de la Salud Pública   (Spain)

Author keywords

Dopamine; Huntington disease; Neuroprotection; Pridopidine

Indexed keywords

3 [3 (METHYLSULFONYL)PHENYL] 1 PROPYLPIPERIDINE; BRAIN DERIVED NEUROTROPHIC FACTOR; HUNTINGTIN; PLACEBO; PRIDOPIDINE; SIGMA 1 OPIATE RECEPTOR; DOPAMINE; DOPAMINE RECEPTOR STIMULATING AGENT; HTT PROTEIN, HUMAN; NERVE PROTEIN; NEUROPROTECTIVE AGENT; PIPERIDINE DERIVATIVE;

ARTICLE; CAG REPEAT; CHOREA; CLINICAL FEATURE; CLINICAL TRIAL (TOPIC); COGNITIVE DEFECT; COORDINATION DISORDER; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MECHANISM; DRUG TOLERABILITY; DYSTONIA; EVIDENCE BASED MEDICINE; GAIT DISORDER; HTT GENE; HUMAN; HUNTINGTON CHOREA; MENTAL DISEASE; META ANALYSIS (TOPIC); MULTICENTER STUDY (TOPIC); NEUROPROTECTION; NONHUMAN; OUTCOME ASSESSMENT; PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL (TOPIC); TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; ANIMAL; GENETICS; HUNTINGTON DISEASE; METABOLISM; PATHOPHYSIOLOGY;

ANIMALS; DOPAMINE; DOPAMINE AGENTS; HUMANS; HUNTINGTIN PROTEIN; HUNTINGTON DISEASE; NERVE TISSUE PROTEINS; NEUROPROTECTIVE AGENTS; PIPERIDINES;

EID: 84945930374     PISSN: None     EISSN: 11778881     Source Type: Journal    
DOI: 10.2147/DDDT.S65738     Document Type: Article

References (45)

1. Dorsey ER, Beck CA, Darwin K, et al; for Huntington Study Group COHORT Investigators. Natural history of Huntington disease. JAMA Neurol. 2013;70(12):1520-1530.
2. van der Burg JM, Björkqvist M, Brundin P. Beyond the brain: widespread pathology in Huntington's disease. Lancet Neurol. 2009;8(8):765-774.
3. Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell. 1993;72(6):971-983.
4. Squitieri F. Neurodegenerative disease: fifty shades of grey in the Huntington's disease gene. Nat Rev Neurol. 2013;9(8):421-422.
5. Ross CA, Tabrizi SJ. Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol. 2011;10(1):83-98.
6. Nasir J, Goldberg YP, Hayden MR. Huntington disease: new insights into the relationship between CAG expansion and disease. Hum Mol Genet. 1996;5(Spec. No.):1431-1435.
7. Subramaniam S, Sixt KM, Barrow R, Snyder SH. Rhes, a striatal protein, mediates mutant huntingtin cytotoxicity. Science. 2009;324(5932):1327-1330.
8. Swarnkar S, Chen Y, Pryor WM, et al. Ectopic expression of the striatal-enriched GTPase Rhes elicits cerebellar degeneration and an ataxia phenotype in Huntington's disease. Neurobiol Dis. 2015;82:66-77.
9. Sciamanna G, Napolitano F, Pelosi B, et al. Rhes regulates dopamine D2 receptor transmission in striatal cholinergic interneurons. Neurobiol Dis. 2015;78:146-162.
10. Huntington G. On chorea. Med Surg Reporter Phila. 1872;26(15):317-321.
11. Reilmann R, Leavitt BR, Ross CA. Huntington's disease: a field on the move. Introduction. Mov Disord. 2014;29(11):1333-1334.
12. Squitieri F, Berardelli A, Nargi E, et al. Atypical movement disorders in the early stages of Huntington's disease: clinical and genetic analysis. Clin Genet. 2000;58(1):50-56.
13. Mestre TA, Ferreira JJ. An evidence-based approach in the treatment of Huntington's disease. Parkinsonism Relat Disord. 2012;18(4):316-320.
14. Mestre T, Ferreira J, Coelho MM, Rosa M, Sampaio C. Therapeutic interventions for symptomatic treatment in Huntington's disease. Cochrane Database Syst Rev. 2009;(3):CD006456.
15. Burgunder JM. Orphan drugs in development for Huntington's disease: challenges and progress. Orphan Drugs Res Rev. 2015;5:1-9.
16. Hadzi TC, Hendricks AE, Latourelle JC, et al. Assessment of cortical and striatal involvement in 523 Huntington disease brains. Neurology. 2012;79(16):1708-1715.
17. Armstrong MJ, Miyasaki JM; for the American Academy of Neurology. Evidence-based guideline: pharmacologic treatment of chorea in Huntington disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2012;79(6):597-603.
18. Reilmann R. Pharmacological treatment of chorea in Huntington's disease-good clinical practice versus evidence-based guideline. Mov Disord. 2013;28(8):1030-1033.
19. Tedroff J, Waters S, Barker AR, Roos R, Squitieri F. Antidopaminergic medication is associated with more rapidly progressive Huntington's Disease. J Huntingtons Dis. 2015;4(2):131-140.
20. 2 dopamine receptor. Br J Pharmacol. 2010;161(6):1343-1350.
21. 2 receptor ligands and the discovery of the dopaminergic stabilizer 4-[3-(methylsulfonyl)phenyl]-1-propylpiperidine (huntexil, pridopidine, ACR16). J Med Chem. 2010;53(6):2510-2520.
22. Feigin A. Pridopidine in treatment of Huntington's disease: beyond chorea? Lancet Neurol. 2011;10(12):1036-1037.
23. Reilmann R. The pridopidine paradox in Huntington's disease. Mov Disord. 2013;28(10):1321-1324.
24. Mulder AH, Draper R, Sminia P, Schoffelmeer AN, Stoof JC. Agonist and antagonist effects of 3-PPP enantiomers on functional dopamine autoreceptors and postsynaptic dopamine receptors in vitro. Eur J Pharmacol. 1985;107(3):291-297.
25. Ponten H, Kullingsjö J, Lagerkvist S, et al. In vivo pharmacology of the dopaminergic stabilizer pridopidine. Eur J Pharmacol. 2010;644(1-3):88-95.
26. 2 receptor occupancy, antipsychotic-like efficacy, and low potential for motor side effects in the rat. J Pharmacol Exp Ther. 2006;318(2):810-818.
27. Rung JP, Rung E, Hegelson L, et al. Effects of (-)-OSU6162 and ACR16 on motor activity in rats, indicating a unique mechanism of dopaminergic stabilization. J Neural Transm. 2008;115(6):899-908.
28. Seeman P, Tokita K, Matsumoto M, Matsuo A, Sasamata M, Miyata K. The dopaminergic stabilizer ASP2314/ACR16 selectively interacts with D2High receptors. Synapse. 2009;63(10):930-934.
29. 2 receptor antagonism and fast receptor dissociation properties. Eur J Pharmacol. 2010;628(1-3):19-26.
30. Carlsson A, Carlsson ML. A dopaminergic deficit hypothesis of schizophrenia: the path to discovery. Dialogues Clin Neurosci. 2006;8(1):137-142.
31. Nilsson M, Carlsson A, Markinhuhta KR, et al. The dopaminergic stabiliser ACR16 counteracts the behavioural primitivization induced by the NMDA receptor antagonist MK-801 in mice: implications for cognition. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(4):677-685.
32. Rung JP, Carlsson A, Markinhuhta KR, Carlsson ML. The dopaminergic stabilizers (-)-OSU6162 and ACR16 reverse (+)-MK-801-induced social withdrawal in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(5):833-839.
33. Sahlholm K, Århem P, Fuxe K, Marcellino D. The dopamine stabilizers ACR16 and (-)-OSU6162 display nanomolar affinities at the σ-1 receptor. Mol Psychiatry. 2013;18(1):12-14.
34. Su TP, Hayashi T, Maurice T, Buch S, Ruoho AE. The sigma-1 receptor chaperone as an inter-organelle signaling modulator. Trends Pharmacol Sci. 2010;31(12):557-566.
35. Miki Y, Tanji K, Mori F, Wakabayashi K. Sigma-1 receptor is involved in degradation of intranuclear inclusions in a cellular model of Huntington's disease. Neurobiol Dis. 2014;74:25-31.
36. Lundin A, Dietrichs E, Haghighi S, et al. Efficacy and safety of the dopaminergic stabilizer pridopidine (ACR16) in patients with Huntington's disease. Clin Neuropharmacol. 2010;33(5):260-264.
37. de Yebenes JG, Landwehrmeyer B, Squitieri F, et al; for the MermaiHD study investigators. Pridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2011;10(12):1049-1057.
38. Huntington Study Group HART Investigators. A randomized, double-blind, placebo-controlled trial of pridopidine in Huntington's disease. Mov Disord. 2013;28(10):1407-1415.
39. Landwehrmeyer B, Marder K, Billmann Ronn B, et al. Effects of the dopaminergic stabilizer pridopidine on motor symptoms in Huntington's disease: a meta-analysis. Presented at: World Congress on Huntington Disease, September 11-14, 2011, Melbourne, Australia.
40. Squitieri F, Landwehrmeyer B, Reilmann R, et al. One-year safety and tolerability profile of pridopidine in patients with Huntington disease. Neurology. 2013;80(12):1086-1094.
41. Huntington Study Group. Unified Huntington's Disease Rating Scale: reliability and consistency. Mov Disord. 1996;11(2):136-142.
42. Esmaeilzadeh M, Kullingsjö J, Ullman H, Varrone A, Tedroff J. Regional cerebral glucose metabolism after pridopidine (ACR16) treatment in patients with Huntington disease. Clin Neuropharmacol. 2011;34(3):95-100.
43. Squitieri F, Di Pardo A, Favellato M, Amico E, Maglione V, Frati L. Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model. J Cell Mol Med. Epub June 22, 2015
44. Wild EJ, Tabrizi SJ. Targets for future clinical trials in Huntington's disease: what's in the pipeline? Mov Disord. 2014;29(11):1434-1445.
45. Ishikawa M, Hashimoto K. The role of sigma-1 receptors in the pathophysiology of neuropsychiatric diseases. J Receptor Ligand Channel Res. 2010;3:25-36.