Recent advances in Alzheimer's disease.pptx

causes of Alzheimer's disease and current treatments and novel treatments. gene therapy and monoclonal antibodies used in Alzheimer's..

1. RECENT ADVANCES IN TREATMENT OF ALZHEIMER’S DISEASE PRESENTED BY ADHIYAMAN P M, M.PHARM. 2 nd SEMESTER, DEPT. OF PHARMACOLOGY, COLLEGE OF PHARMACY-SRIPMS .

2. 2

3. Alzheimer’s disease is the most common form of dementia. Progressive disease that destroys memory and other important mental functions. Brain cell connections and the cells themselves degenerate and die. 3

4. 4

5. 5

6. 6

7. 7

8. Stabilizes microtubules Destabilized microtubules 8

9. 9

10. 10

11. 11

12. Piracetam Neuroprotection Restored neurotransmission Improved neuronal function Enhanced neuroplasticity Side effects   Gastric discomfort I nsomnia D izziness Skin rash 12

13. 13 Ginkgo biloba Cognition enhancer Antioxidant Increase blood flow Altitude sickness Side effects Increased risk of bleeding Allergic skin reaction Gastric discomfort

14. 14

15. Amyloid precursor protein (APP), presenilin (PSEN1) & PSEN2 genes encode APP metabolism and Aβ generation. Overexpression of APP causing cellular and molecular alteration. β -site amyloid precursor protein cleaving enzyme( BACE1) involved in the cleavage of APP. siRNA - APP targeted gene therapy CRISPR-Cas9 suppress Aβ associated pathway 15

16. Apolipoprotein E (APOE) transporter of lipids . APOE2, APOE3 and APOE4 which carries different risk percentage and differs due to presence of cysteine(112) or arginine(158) . APOE4 which increase levels of amyloid while APOE2 has a lower amyloid burden. I ncrease the expression level of APOE2 which prevent A β deposition. 16

17. 17

18. V AN1792 - synthetic Aβ which bound saponin adjuvant QS-21 (Phase 2). Removal of amyloid plague. CAD106, peptide vaccines carrying Aβ N-terminus representing B cell epitope (Phase 2). E nhanced tolerability and safety profiles. 18

19. Name of the drugs Stages Aducanumab Phase 4 ALZ 801 Phase 1 BAN2401 Phase 3 Bapineuzumab Phase 3 Crenezumab Phase 3 Ponezumab Phase 2 Solanezumab Phase 3 19

20. 20

21. PASSIVE IMMUNIZATION Bapineuzumab is an lgG1 antibody that binds fibrillar and soluble A β and activates microglial phagocytosis and (Phase 3). 21

22. APP processed by α -secretase within A β sequence and generate soluble neurotrophic sAPP α . Accumulation of A β in brain leads to oxidative stress, neuronal dysfunction. Secondary prevention of AD can be made by: D ecreasing the production of Aβ S timulation of clearance of Aβ formed P revention of aggregation of Aβ into amyloid plaques 22

23. D ecreasing Aβ neurotoxicity or inhibiting its aggregation have therapeutic potentials. β-sheet breaker iAβ5p, which showed improved spatial memory and decreased amyloid plaque deposits ( P hase 2). Upregulation of α-secretase activity which decrease the amount of APP. Deprenyl, increase α-secretase activity by promoting ADAM10 and PKC. Aβ-AGGREGATION INHIBITORS 23

24. BACE1 inhibitor L owering of brain Aβ40 and Aβ42. Decreased APPβ and an increased sAPPα secretion. KMI-429 reduce Aβ production ( P hase 2). BMS-299897 and MRK560 is a γ-secretase inhibitors (Phase 1 & 3). γ-secretase modulators, shifting the γ-secretase cutting point to produce shorter, non-toxic Aβ fragments. 24

25. P hosphorylation of tau is controlled by different kinases and phosphatases. The protein phosphatase (PP)-2A increase dephosphorylation of tau. Cyclin-dependent kinase-5 (CDK5) and Glycogen synthase kinase (GSK)-3β which phosphorylate tau in AD. AF267B – inhibit GSK-3 β 25

26. Current therapies providing temporary improvement and reducing the rate of cognitive decline. Gene therapy appear is a alternative therapeutics strategy. Identifying potential therapeutic compounds. 26

27. Hong-Qi Y, Zhi-Kun S, Sheng-Di C. Current advances in the treatment of Alzheimer’s disease: Focused on c onsiderations t argeting Aβ and Tau. Transl N eurodegener . 2012; 1(21): 2-9. Marei HE, Althani1 A, Suhonen J, Zowalaty1 ME, Albanna ME, Cenciarelli C, Wang T, Caceci T. Recent perspective a bout the amyloid c ascade h ypothesis and stem c ell - b ased t herapy in the treatment of Alzheimer’s disease. FCDR. 2016; 5: 3-33. Rang HP, Dale MM, Ritter JM, Flower R, Henderson G. Pharmacology: Neurodegenerative d iseases. 9 th ed. Edinburg: Elseveir Ltd; 2020. Standaert DG, Roberson ED. Treatment of c entral n ervous s ystem d egenerative d isorders. In: Brunton LL, Chabner BA, Knollman BC. Goodman & Gilman’s The p harmacological basis of therapeutics. 12 th ed. New Y ork: McGraw - hill m edical publishers; 2011. Thoe ES, Fauzi A, Tang YQ, Chamyuang S, Chia YA. A review on advances of treatment modalities for Alzheimer’s disease. Life Sci. 2021; 276: 1-15. Tripathi KD. Essentials of medicinal pharmacology. 8 th ed. New delhi: Jaypee medical p ublishers; 2019. 27

28. 28