New approaches to the treatment of frontotemporal lobar degeneration

Current Opinion in Neurology

Volumn 21, Issue 6, 2008, Pages 708-716

  Vossel, Keith A ^a,b   Miller, Bruce L ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Frontotemporal; Progranulin; Tau; Transactive response DNA binding protein 43; Treatment

Indexed keywords

A 705253; AMFEBUTAMONE; ANTHRAQUINONE DERIVATIVE; ANTIDEPRESSANT AGENT; ATYPICAL ANTIPSYCHOTIC AGENT; CHOLINERGIC RECEPTOR BLOCKING AGENT; CITALOPRAM; DARIFENACIN; DONEPEZIL; DOPAMINE; DOPAMINE RECEPTOR STIMULATING AGENT; ESCITALOPRAM; FLUOXETINE; FLUVOXAMINE; GALANTAMINE; LITHIUM; MEMANTINE; OXYBUTYNIN; PAROXETINE; PLACEBO; PROGRANULIN; PTC 124; REMBER; RILUZOLE; SERTRALINE; TACROLIMUS; TAU PROTEIN; TOLTERODINE; TOPIRAMATE; TRAZODONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID;

ADULT; AGGRESSION; AGITATION; ALZHEIMER DISEASE; APATHY; BEHAVIOR CHANGE; BEHAVIOR DISORDER; BLOOD PRESSURE; CLINICAL ASSESSMENT; CLINICAL TRIAL; COGNITIVE DEFECT; COMPREHENSION; CONFUSION; CONSTIPATION; DEGENERATIVE DISEASE; DELUSION; DEMENTIA; DEPRESSION; DIET; DRUG MEGADOSE; EXTRAPYRAMIDAL SYMPTOM; FAMILY; FOOD; FRONTOTEMPORAL DEMENTIA; FRONTOTEMPORAL LOBAR DEGENERATION; HIGH THROUGHPUT SCREENING; HUMAN; INCONTINENCE; INSOMNIA; MICROTUBULE; MOTOR DYSFUNCTION; MOTOR NEURON DISEASE; PARKINSONISM; PREVALENCE; PRIMARY PROGRESSIVE APHASIA; PROGRESSIVE NONFLUENT APHASIA; PSYCHOSIS; REVIEW; SEDATION; SEMANTIC DEMENTIA; SIDE EFFECT; SLEEP DISORDER; SOMNOLENCE; WEIGHT GAIN;

ANIMALS; DEMENTIA; DNA-BINDING PROTEINS; EXCITATORY AMINO ACID ANTAGONISTS; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; MEMANTINE; TAUOPATHIES;

EID: 56749095159     PISSN: 13507540     EISSN: None     Source Type: Journal    
DOI: 10.1097/WCO.0b013e328318444d     Document Type: Review

References (99)

1. Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51:1546-1554.
2. Rosen HJ, Gorno-Tempini ML, Goldman WP, et al. Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology 2002; 58:198-208.
3. Mendez MF, Licht EA, Shapira JS. Changes in dietary or eating behavior in frontotemporal dementia versus Alzheimer's disease. Am J Alzheimers Dis Other Demen 2008; 23:280-285.
4. Swartz JR, Miller BL, Lesser IM, et al. Behavioral phenomenology in Alzheimer's disease, frontotemporal dementia, and late-life depression: a retrospective analysis. J Geriatr Psychiatry Neurol 1997; 10:67-74.
5. Liu W, Miller BL, Kramer JH, et al. Behavioral disorders in the frontal and temporal variants of frontotemporal dementia. Neurology 2004; 62:742-748.
6. Miller BL. Frontotemporal dementia and semantic dementia: anatomic variations on the same disease or distinctive entities? Alzheimer Dis Assoc Disord 2007; 21:S19-S22. This study reviews classification of FTLD subtypes in context of recent genetic and neuropathologic findings.
7. Evans JJ, Heggs AJ, Antoun N, Hodges JR. Progressive prosopagnosia associated with selective right temporal lobe atrophy. A new syndrome? Brain 1995; 118 (Pt 1):1-13.
8. Rosen HJ, Perry RJ, Murphy J, et al. Emotion comprehension in the temporal variant of frontotemporal dementia. Brain 2002; 125 (Pt 10):2286-2295.
9. Rankin KP, Gomo-Tempini ML, Allison SC, et al. Structural anatomy of empathy in neurodegenerative disease. Brain 2006; 129 (Pt 11):2945-2956.
10. Edwards-Lee T, Miller BL, Benson DF, et al. The temporal variant of frontotemporal dementia. Brain 1997; 120 (Pt 6):1027-1040.
11. Seeley WW, Bauer AM, Miller BL, et al. The natural history of temporal variant frontotemporal dementia. Neurology 2005; 64:1384-1390.
12. Josephs KA, Duffy JR, Strand EA, et al. Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 2006; 129 (Pt 6):1385-1398.
13. Banks SJ, Weintraub S. Neuropsychiatric symptoms in behavioral variant frontotemporal dementia and primary progressive aphasia. J Geriatr Psychiatry Neurol 2008; 21:133-141. This study illustrates the overlapping neuropsychiatric symptoms between PPA and bvFTD.
14. Mesulam MM. Rimary progressive aphasia - differentiation from Alzheimer's disease. Ann Neurol 1987; 22:533-534.
15. Strong MJ, Lomen-Hoerth C, Caselli RJ, et al. Cognitive impairment, frontotemporal dementia, and the motor neuron diseases. Ann Neurol 2003; 54 (Suppl 5):S20-S23.
16. Alladi S, Xuereb J, Bak T, et al. Focal cortical presentations of Alzheimer's disease. Brain 2007; 130 (Pt 10):2636-2645. This important clinical-pathological study provides frequency of Alzheimer's disease pathology in patients presenting with progressive focal cortical syndromes.
17. Rabinovici GD, Furst AJ, O'Neil JP, et al. 11C-RB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology 2007; 68:1205-1212.
18. Boxer AL, Boeve BF. Frontotemporal dementia treatment: current symptomatic therapies and implications of recent genetic, biochemical, and neuroimaging studies. Alzheimer Dis Assoc Disord 2007; 21:S79-S87. This comprehensive review discusses clinical trials for patients with FTLD published through January 2007.
19. Lebert F, Stekke W, Hasenbroekx C, et al. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dement Geriatr Cogn Disord 2004; 17:355-359.
20. Huey ED, Putnam KT, Grafman J. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology 2006; 66:17-22.
21. Diehl-Schmid J, Forstl H, Perneczky R, et al. A 6-month, open-label study of memantine in patients with frontotemporal dementia. Int J Geriatr Psychiatry 2008; 23:754-759.
22. Kertesz A, Morlog D, Light M, et al. Galantamine in frontotemporal dementia and primary progressive aphasia. Dement Geriatr Cogn Disord 2008; 25:178-185. This is the first clinical trial to study the efficacy of galantamine to treat FTLD.
23. Cruz M, Marinho V, Fontenelle LF, et al. Topiramate may modulate alcohol abuse but not other compulsive behaviors in frontotemporal dementia: case report. Cogn Behav Neurol 2008; 21:104-106.
24. Anneser JM, Jox RJ, Borasio GD. Inappropriate sexual behaviour in a case of ALS and FTD: successful treatment with sertraline. Amyotroph Lateral Scler 2007; 8:189-190.
25. Swanberg MM. Memantine for behavioral disturbances in frontotemporal dementia: a case series. Alzheimer Dis Assoc Disord 2007; 21:164-166.
26. Eslinger PJ, Moore P, Troiani V, et al. Oops! Resolving social dilemmas in frontotemporal dementia. J Neurol Neurosurg Psychiatry 2007; 78:457-460.
27. Miller BL, Chang L, Mena I, et al. Progressive right frontotemporal degeneration: clinical, neuropsychological and SPECT characteristics. Dementia (Basel, Switzerland) 1993; 4 (3-4):204-213.
28. Lough S, Kipps CM, Treise C, et al. Social reasoning, emotion and empathy in frontotemporal dementia. Neuropsychologia 2006; 44:950-958.
29. Rankin KP, Kramer JH, Mychack P, Miller BL. Double dissociation of social functioning in frontotemporal dementia. Neurology 2003; 60:266-271.
30. Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology 1997; 48 (5 Suppl 6):S10-S16.
31. Gauthier S, Wirth Y, Mobius HJ. Effects of memantine on behavioural symptoms in Alzheimer's disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies. Int J Geriatr Psychiatry 2005; 20:459-464.
32. Cummings JL, Schneider E, Tariot PN, Graham SM. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology 2006; 67:57-63.
33. Franco KN, Messinger-Rapport B. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. J Am Med Dir Assoc 2006; 7:201-202.
34. Rosen HJ, Allison SC, Schauer GF, et al. Neuroanatomical correlates of behavioural disorders in dementia. Brain 2005; 128 (Pt 11):2612-2625.
35. Goetz CG, Tanner CM, Klawans HL. Bupropion in Parkinson's disease. Neurology 1984; 34:1092-1094.
36. Woolley JD, Gorno-Tempini ML, Seeley WW, et al. Binge eating is associated with right orbitofrontal-insular-striatal atrophy in frontotemporal dementia. Neurology 2007; 69:1424-1433.
37. Swartz JR, Miller BL, Lesser IM, Darby AL. Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors. J Clin Psychiatry 1997; 58:212-216.
38. Mendez MF, Shapira JS, McMurtray A, Licht E. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatry 2007; 15:84-87.
39. Kertesz A, Blair M, McMonagle P, Munoz DG. The diagnosis and course of frontotemporal dementia. Alzheimer Dis Assoc Disord 2007; 21:155-163.
40. Scaravilli T, Pramstaller PP, Salerno A, et al. Neuronal loss in Onuf's nucleus in three patients with progressive supranuclear palsy. Ann Neurol 2000; 48:97-101.
41. Goldman JS, Farmer JM, Wood EM, et al. Comparison of family histories in FTLD subtypes and related tauopathies. Neurology 2005; 65:1817-1819.
42. Hutton M, Lendon CL, Rizzu P, et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 1998; 393:702-705.
43. Poorkaj P, Bird TD, Wijsman E, et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol 1998; 43:815-825.
44. Spillantini MG, Crowther RA, Kamphorst W, et al. Tau pathology in two Dutch families with mutations in the microtubule-binding region of tau. Am J Pathol 1998; 153:1359-1363.
45. Wilhelmsen KC. Frontotemporal dementia genetics. J Geriatr Psychiatry Neurol 1998; 11:55-60.
46. Baker M, Mackenzie IR, Pickering-Brown SM, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 2006; 442:916-919.
47. Cruts M, Gijselinck I, van der Zee J, et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 2006; 442:920-924.
48. Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314:130-133.
49. Josephs KA, Lin WL, Ahmed Z, et al. Frontotemporal lobar degeneration with ubiquitin-positive, but TDP-43-negative inclusions. Acta Neuropathol 2008; 116:159-167.
50. Mackenzie IR, Foti D, Woulfe J, Hurwitz TA. Atypical frontotemporal lobar degeneration with ubiquitin-positive, TDP-43-negative neuronal inclusions. Brain 2008; 131 (Pt 5):1282-1293. This work describes the unique clinical-pathological features of TDP-43 negative FTLD-U disorder.
51. Gitcho MA, Baloh RH, Chakraverty S, et al. TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 2008; 63:535-538. This landmark study describes a TDP-43 mutation linked to a dominantly inherited neurodegenerative disease.
52. Cairns NJ, Bigio EH, Mackenzie IR, et al. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 2007; 114:5-22.
53. Hodges JR, Davies RR, Xuereb JH, et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol 2004; 56:399-406.
54. Llado A, Sanchez-Valle R, Rey MJ, et al. Clinicopathological and genetic correlates of frontotemporal lobar degeneration and corticobasal degeneration. J Neurol 2008; 255:488-494.
55. Sha S, Hou C, Viskontas IV, Miller BL. Are frontotemporal lobar degeneration, progressive supranuclear palsy and corticobasal degeneration distinct diseases? Nat Clin Pract Neurol 2006; 2:658-665.
56. Trojanowski JQ, Duff K, Fillit H, et al. New directions for frontotemporal dementia drug discovery. Alzheimer Demen 2008; 4:89-93. This important review provides a conceptual framework for approaches to FTLD treatment.
57. Wang JZ, Liu F. Microtubule-associated protein tau in development, degeneration and protection of neurons. Prog Neurobiol 2008; 85:148-175. This is one of the most comprehensive reviews available on tau structure, biological function, and potential roles in neurodegeneration.
58. Mazanetz MP, Fischer PM. Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases. Nat Rev Drug Discov 2007; 6:464-479. This detailed review illustrates how tau kinases may serve as a therapeutic target in tau-mediated neurodegeneration.
59. Churcher I. Tau therapeutic strategies for the treatment of Alzheimer's disease. Curr Top Med Chem 2006; 6:579-595.
60. Noble W, Planel E, Zehr C, et al. Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo. Proc Natl Acad Sci U S A 2005; 102:6990-6995.
61. Engel T, Goni-Oliver P, Lucas JJ, et al. Chronic lithium administration to FTDP-17 tau and GSK-3beta overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but preformed neurofibrillary tangles do not revert. J Neurochem 2006; 99:1445-1455.
62. De Sarno P, Li X, Jope RS. Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium valproate and lithium. Neuropharmacology 2002; 43:1158-1164.
63. Crowe A, Ballatore C, Hyde E, et al. High throughput screening for small molecule inhibitors of heparin-induced tau fibril formation. Biochem Biophys Res Commun 2007; 358:1-6.
64. Pickhardt M, von Bergen M, Gazova Z, et al. Screening for inhibitors of tau polymerization. Curr Alzheimer Res 2005; 2:219-226.
65. Pickhardt M, Gazova Z, von Bergen M, et al. Anthraquinones inhibit tau aggregation and dissolve Alzheimer's paired helical filaments in vitro and in cells. J Biol Chem 2005; 280:3628-3635.
66. Roberson ED, Scearce-Levie K, Palop JJ, et al. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science 2007; 316:750-754.
67. SantaCruz K, Lewis J, Spires T, et al. Tau suppression in a neurodegenerative mouse model improves memory function. Science 2005; 309:476-481.
68. Dickey CA, Ash P, Klosak N, et al. Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. Mol Neurodegener 2006; 1:6.
69. Sinjoanu RC, Kleinschmidt S, Bitner RS, et al. The novel calpain inhibitor A-705253 potently inhibits oligomeric beta-amyloid-induced dynamin 1 and tau cleavage in hippocampal neurons. Neurochem Int 2008; 53 (3-4):79-88.
70. Yoshiyama Y, Higuchi M, Zhang B, et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 2007; 53:337-351.
71. Dickey CA, Kamal A, Lundgren K, et al. The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. J Clin Invest 2007; 117:648-658.
72. Schneider A, Mandelkow E. Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics 2008; 5:443-457.
73. Park JW, Parisky K, Celotto AM, et al. Identification of alternative splicing regulators by RNA interference in Drosophila. Proc Natl Acad Sci U S A 2004; 101:15974-15979.
74. Zhang B, Maiti A, Shively S, et al. Microtubule-binding drugs offset tau sequestration by stabilizing microtubules and reversing fast axonal transport deficits in a tauopathy model. Proc Natl Acad Sci U S A 2005; 102:227-231.
75. Divinski I, Holtser-Cochav M, Vulih-Schultzman I, et al. Peptide neuroprotection through specific interaction with brain tubulin. J Neurochem 2006; 98:973-984.
76. Vulih-Shultzman I, Pinhasov A, Mandel S, et al. Activity-dependent neuroprotective protein snippet NAP reduces tau hyperphosphorylation and enhances learning in a novel transgenic mouse model. J Pharmacol Exp Ther 2007; 323:438-449. This work discusses the novel drug NAPVSIPQ NAP and provides evidence for its neuroprotective role using transgenic mouse models.
77. Ahmed Z, Mackenzie IR, Hutton ML, Dickson DW. Progranulin in frontotemporal lobar degeneration and neuroinflammation. J Neuroinflammation 2007; 4:7.
78. Van Damme P, Van Hoecke A, Lambrechts D, et al. Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. J Cell Biol 2008; 181:37-41. This translational study supports a role for progranulin in neuronal survival.
79. Welch EM, Barton ER, Zhuo J, et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature 2007; 447:87-91.
80. Du M, Liu X, Welch EM, et al. PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model. Proc Natl Acad Sci U S A 2008; 105:2064-2069.
81. Buratti E, Dork T, Zuccato E, et al. Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. EMBO J 2001; 20:1774-1784.
82. Ballatore C, Lee VM, Trojanowski JQ. Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat Rev Neurosci 2007; 8:663-672. This review provides an excellent overview of tau-mediated neurodegeneration.
83. Gijselinck I, Van Broeckhoven C, Cruts M. Granulin mutations associated with frontotemporal lobar degeneration and related disorders: an update. Hum Mutat 2008 [Epub ahead of print]. This work provides an updated list of null mutations in the progranulin gene linked to familial FTLD.
84. Mackenzie IR, Baker M, Pickering-Brown S, et al. The neuropathology of frontotemporal lobar degeneration caused by mutations in the progranulin gene. Brain 2006; 129 (Pt 11):3081-3090.
85. He Z, Bateman A. Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumongenesis. J Mol Med 2003; 81:600-612.
86. Bruni AC, Moment P, Bernardi L, et al. Heterogeneity within a large kindred with frontotemporal dementia: a novel progranulin mutation. Neurology 2007; 69:140-147.
87. Mercado PA, Ayala YM, Romano M, et al. Depletion of TDP 43 overrides the need for exonic and intronic splicing enhancers in the human apoA-II gene. Nucleic Acids Res 2005; 33:6000-6010.
88. Liscic RM, Grinberg LT, Zidar J, et al. ALS and FTLD: two faces of TDP-43 proteinopathy. Eur J Neurol 2008; 15:772-780. This important review discusses the genetic and neuropathological underpinnings of TDP-43 proteinopathies.
89. Zhang YJ, Xu YF, Dickey CA, et al. Progranulin mediates caspase-dependent cleavage of TAR DNA binding protein-43. J Neurosci 2007; 27:10530-10534. This is the first study to demonstrate a cellular pathway linking progranulin and TDP-43.
90. Rohn TT. Caspase-cleaved TAR DNA-binding protein-43 is a major pathological finding in Alzheimer's disease. Brain Res 2008; 1228:189-198. This neuropathological study revealed extensive TDP-43 pathology in Alzheimer's disease brains, using a novel antibody that recognized caspase-cleaved TDP-43.
91. Watts GD, Wymer J, Kovach MJ, et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet 2004; 36:377-381.
92. Skibinski G, Parkinson NJ, Brown JM, et al. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat Genet 2005; 37:806-808.
93. Waugh MG, Minogue S, Anderson JS, et al. Localization of a highly active pool of type II phosphatidylinositol 4-kinase in a p97/valosin- containing-protein-rich fraction of the endoplasmic reticulum. Biochem J 2003; 373 (Pt 1):57-63.
94. Wojcik C. VCP - the missing link in protein degradation? Trends Cell Biol 2002; 2:212.
95. Braun RJ, Zischka H. Mechanisms of Cdc48/VCP-mediated cell death: from yeast apoptosis to human disease. Biochim Biophys Acta 2008; 1783:1418-1435. This comprehensive review discusses the role of mutant VCP in cell death pathways, and in particular, apoptosis.
96. Mehta SG, Watts GD, Adamson JL, et al. APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD). Genet Med 2007; 9:9-13.
97. Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proc Natl Acad Sci U S A 2006; 103:5644-5651.
98. Lee JA, Beigneux A, Ahmad ST, et al. ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr Biol 2007; 17:1561-1567.
99. van der Zee J, Urwin H, Engelborghs S, et al. CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro. Hum Mol Genet 2008; 17:313-322.