Future Pharmacological Armamentaria in Management of Alzheimer Disease

Authors

  • Megha H Shah B.J. Medical College, Ahmedabad
  • Hetal D Shah Narayana Hrudalaya, Ahmedabad
  • Vipul P Chaudhari Government Medical College, Surat

Keywords:

Alzheimer Disease, Management, Dementia

Abstract

Introduction: Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder and common cause of dementia in elderly. With advancing age, number of people suffering from AD is also increased. Exact aetiology of AD was not known and therapy was focused mainly on increasing central cholinergic transmission with drugs like donepazil, reivastigmine and galantamine. With the generation of amyloid hypothesis, extracellular amyloid plaques, consisting of amorphous extra cellular deposits of β-amyloid protein (known as Aβ) and intraneuronal neurofibrillary tangles(Tau) mainly in the hippocampus and frontal cortex ,altered processing of amyloid protein from its precursor (amyloid precursor protein, APP) recognised as the key to the pathogenesis of AD. But, now various studies have shown that etiology may be multifactorial. Inspite of having identified many potential targets, currently no drug modifying disease pathology is available .Advancement of the early diagnostic methods like positron emission tomography (PET) scan and measurement of various biomarkers like NO tagged proteins, ADAM-10 in c.s.f. could potentiate research to develop disease modifying drugs. Drugs modifying Y secretase, tyrosine kinase inhibitors, sigma receptor agonists, anti-Aβ monoclonal Abs are in the various stages of drug development and could become the cornerstone in the management of AD in future.

Methods: Reviews from index journals and books were taken in this study. In this process, we identified 276 possible sources of information which, upon further scrutiny, were eventually reduced to 30 appropriate studies for inclusion in the review.

Conclusion: Understanding the role and extent of factors causing AD, robust designing of RCTs with use of various biomarkers and multitargeted therapeutic approach are required to develop disease modifying drug which can ameliorate suffering of alzheimer disease patients.

References

William H. Waugh. A Call to Reduce the Incidence of Alzheimer’s disease. The Journal of Applied Research, 2010,10;(2):53-7

H.P.Rang, M.M.Dale, J.M. Ritter. ‘’Pharmacology’’. 7th edition, Chapter 36.Elseiver publication (Singapore), 2007.

Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med 2010; 362: 329-44.

http://www.philly.com/philly/health/20120410_Avid_s_diagnostic_aid_for_Alzheimer_s_gets_FDA_approval.html?cmpid=138896554#ixzz1rdwnN700

Guy M. McKhanna, David S. Knopmanc, Howard Chertkowd, Bradley T. Hymanf, Clifford R. Jack, Jr.g, Claudia H. Kawash et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia 7 (2011): 263–69.

Heinrich JN, Butera JA, Carrick T, et al. Pharmacological comparison of uscarinic ligands: historical versus more recent muscarinic M1-preferring receptor agonists. Eur J Pharmacol 2009; 605: 53–56.

Frolich L, Eckerwall G, Jonas N, Sirocco-Investigators. A multicenter, double-blind, placebo-controlled phase IIB proof-ofconcept dose-ranging study of AZD3480 and donepezil over 12 weeks in patients with mild to moderate Alzheimer’s disease. Alzheimers Dement 2009; 5 (4 suppl 1): 85.

Martin R. Farlow, Stephen Salloway, Pierre N. Tariot, , Margaret L. Moline, Qin Wang et al.Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer's disease: A 24-week, randomized, double-blind study. Clinical Therapeutics, 2010, 32(7); 1234-51.

G Lefèvre, G Sdek, S S Jhee, M T Leibowitz, H-La Huang, A Enz et al. Pharmacokinetics and Pharmacodynamics of the Novel Daily Rivastigmine Transdermal Patch Compared With Twice-daily Capsules in Alzheimer's Disease Patients. Clinical Pharmacology & Therapeutics 2008, 83; 106-14.

Wilcock GK, Black SE, Hendrix SB, Zavitz KH, Swabb EA, Laughlin MA. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. Lancet Neurol. 2008, (7):483-93.

Green RC, Schneider LS, Amato DA, Beelen AP, Wilcock G, Swabb EA, Zavitz KH. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial. JAMA. 2009; 302:2557-64.

Vellas B, Sol O, Snyder P, Ousset PJ, Haddad R, Maurin M, Lemarié JC, Désiré L, and Pando M. EHT 0202 in Alzheimer's disease: a 3-month, randomized, placebo-controlled double-blind study. Current Alzheimer Research, 2011; 8 (2), 203-12.

Peer-Hendrik Kuhn, Huanhuan Wang, Bastian Dislich, Alessio Colombo, Ulrike Zeitschel, Joachim W. Ellwart, Elisabeth Kremmer, Steffen Roßner, and Stefan F. Lichtenthaler. DAM10 is the Physiologically Relevant, Constitutive Alpha-Secretase of the Amyloid Precursor Protein in Primary Neurons. The EMBO Journal, 2010, 29: 3020-32.

Cai G, Atzmon G, Naj AC, Beecham GW, Barzilai N, Haines JL, Sano M, Pericak-Vance M, Buxbaum JD. Evidence against a role for rare ADAM10 mutations in sporadic Alzheimer Disease. Neurobiol Aging; 2012; 33 (2):416-417.

Landreth G, Jiang Q, Mandrekar S, Heneka M. PPARgamma agonists as therapeutics for the treatment of Alzheimer’s disease. Neurotherapeutics 2008; 5: 481–89.

Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M, Sabbagh M, Honig LS, Doody R, van Dyck CH, Mulnard R, Barakos J, Gregg KM, Liu E, Lieberburg I, Schenk D, Black R, Grundman M. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2009; 73:2061-70.

Rinne JO, Brooks DJ, Rossor MN, Fox NC, Bullock R, Klunk WE, Mathis CA, Blennow K, Barakos J, Okello AA, Rodriguez Martinez de Liano S, Liu E, Koller M, Gregg KM, Schenk D, Black R, Grundman M. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol. 2010; 9:363-72.

Tsakanikas D, Shah K, Flores C, Assuras S, Relkin NR. Effects of uninterrupted intravenous immunoglobulin treatment of Alzheimer’s disease for nine months. Alzheimers Dement 2008; 4 (4 suppl 2): 776

Matsuoka Y, Gray AJ, Hirata-Fukae C, et al. Intranasal NAP administration reduces accumulation of amyloid peptide and tau hyperphosphorylation in a transgenic mouse model of Alzheimer’s disease at early pathological stage. J Mol Neurosci 2007; 31: 165–70.

Schmechel DE, Gerard G, Vatakis NG, et al. A phase 2, double-blind, placebo-controlled study to evaluate the safety, tolerability, and eff ect on cognitive function of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment. Alzheimers Dement 2008; 4 (4 suppl 2): 483.

Piette F, Belmin J, Vincent H, Schmidt N, Pariel S, Verny M, Marquis C, Mely J, Hugonot-Diener L, Kinet JP, Dubreuil P, Moussy A, Hermine O .Masitinib as an adjunct therapy for mild to moderate Alzheimer’s disease: a randomised, placebo-controlled phase 2 trial. Alzheimer’s Research & Therapy, 2011;3 (2):16.

Mishina, M.,Ohyama,M., Ishii, K., Kitamura, S., Kimura,Y.,Oda, K., et al. Low density of sigma-1 receptors in early Alzheimer's disease. Ann Nucl Med;2008; 22,151-6.

Espallergues J., Lapalud P., Christopoulos A., Avlani V.A., Sexton P.M., Vamvakides A. and Maurice T. “Involvement of the sigma1 (s1) receptor in the antiamnesic, but not antidepressant-like, effects of the aminotetrahydrofuran derivative ANAVEX 1-41”. British Journal of Pharmacology, 2007; 152 (2): 267–79.

Hemachand Tummala, Xiaofan Li and Ramin Homayouni .Interaction of a novel mitochondrial protein, 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1), with the amyloid precursor protein family. European Journal of Neuroscience, 2010;31:1926–34.

Nelson O, Tu H, Lei T, Bentahir M,de Strooper B, Bezprozvanny I. Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of Presenilin 1. J Clin Invest 2007; 117: 1230-9.

M D M Haag, A Hofman, P J Koudstaal, B H C Stricker, M M B Breteler.Satins Study. J Neurol Neurosurg Psychiatry, 2009; 80:13-7.

Feldman HH, Doody RS, Kivipelto M, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology 2010; 74: 956–64.

Firuzi O, Zhuo J, Chinnici CM, Wisniewski T, PraticÒ D. 5-Lipoxygenase gene disruption reduces amyloid-β pathology in a mouse model of Alzheimer's disease. FASEB J.2008; 22:1169-78.

Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem, 2004; 11:1135-46.

Ning Chen, Jennifer Newcomb, Svitlana Garbuzova-Davis, Cyndy Davis Sanberg, Paul R. Sanberg,and Alison E. Human Umbilical Cord Blood Cells Have Trophic Effects on Young and Aging Hippocampal Neurons. Aging and disease, 2010; 1(3) :173.

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Published

2013-03-31

How to Cite

1.
Shah MH, Shah HD, Chaudhari VP. Future Pharmacological Armamentaria in Management of Alzheimer Disease. Natl J Community Med [Internet]. 2013 Mar. 31 [cited 2024 Dec. 22];4(01):109-16. Available from: https://njcmindia.com/index.php/file/article/view/1471

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Original Research Articles