Ministry of Science, Technology & Innovation Malaysia

Lampiran II

PROGRESS AND FINANCIAL REPORT

Year : ______2015______

A. PROJECT DETAILS
Project number: 02-01-01-SF0576
Project title: Ciproxifan, a Histamine H3 Antagonist as a Potential Therapeutic agent in
Alzheimer’s Disease
Project leader: Dr Vasudevan Mani
Project Duration : __30_____ (months) (6 month extension)
Project Start date : __March_____(month)__2013_____(year)
Project End date :____August ____(month)___2015____(year)
Tel:_ 0332584611____Fax : ___0332584602______E-mail : ___
B. FINANCIAL PROGRESS
i. Approved Project Allocation : RM__237,000____
Year 1 ( 2013_) : RM_128,000__ Year 2 (2014_) : RM_109,000__ Year 3 (20 __ __) : RM______
ii. Total Allocation Received Todate : RM_237,000____
iii. Total Expenditure Todate: RM___185,604.41_ or _78.31%(Total Expenditure / Total Allocation received X 100 )
iv. Balance of Allocation Todate : RM__51,395.59_____ (Total Allocation received – Total Expenditure)
v. Actual Project Expenditure (Please report total cumulative expenditure up to the past report period)
Report Period : / ü / Mac-May / Jun-Aug / Sept-Nov / Dec-Feb
Project Cost Components / Total Approved Budget ( RM) / Total Allocation Received (RM) / Total
Cumulative Expenditure (RM)
· Temporary and contract personnel (V11000) / 74,000.00 / 74,000.00 / 53,300.00
· Travel and transportation (V21000) / 7,000.00 / 7,000.00 / 244.00
· Rentals (V24000) / 0.00 / 0.00 / 0.00
· Research materials and supplies (V26000) / 140,000.00 / 140,000.00 / 130,710.41
· Minor modifications and repairs (V28000) / 0.00 / 0.00 / 0.00
· Special services (V29000) / 16,000.00 / 16,000.00 / 1350.00
· Special equipment and accessories (V35000) / 0.00 / 0.00 / 0.00
Total direct expenses
Total / 237,000.00 / 237,000.00 / 185,604.41
Is this performance in line with plan? / ü / Yes / No (Please complete para vi and vii)
Vi. Reasons for variations from budget (Please provide the reasons)
The partial second year allocation (RM 54,500) was received recently. So we are requesting to allow the remaining money to spend another three months more, before the submission of final report.
vii. Proposed corrective action (Please give details of the proposed action)
Results from in vitro BACE- inhibition and Aβ1-40 and Aβ1-42 are indicating that there are no significant changes of ciproxifan on amyloid levels. Now we are focusing to explore other related mechanisms listed as cholinergic stimulation, encounter oxidative stress and control neuroinflammation
C. Regulatory Compliance (Please provide softcopy and hardcopy of the documents) if any
Yes / No / Date of approval
1 / Animal Ethics Approval / ü / 26-04-2013
2 / Human Ethics Approval
3 / National Biosafety Board (NBB) Notification/Approval
D. RESEARCH PROGRESS
1.0. Milestone Achievement
No / Planned Milestones / Planned Milestone Date (month/year) / Achieved* (Yes/No) / Actual Completion Date (month/year)
M1 / In-vitro BACE1 and neurotoxicity on SK-N-SH
cells determined / 05/2013 / Yes / 09/2013
M2 / Effect on memory models tested / 09/2013 / Yes / 12/2013
M3 / APP , down streams and other related evaluated / 02/2014 / Yes / 02/2015
M4 / Beta – and Gamma – secretase levels evaluated / 06/2014 (04/2015) / Yes / 06/2015
M5 / Immunohistological study / 12/2014 (06/2015) / No / On progress
M6 / Project completion / 02/2015 (08/2015) / No
* If YES please provide details description of the milestone achieved in (1.1), include data,tables,figures, etc
* If NO please give the reason for non-achievement of the milestone in (1.2)
(1.1) Milestones description/
Summary of the Progress / Use separate sheets
(1.2) Non-achievement / 1.2.1 Reason for non-achievement :
The results of ciproxifan on APP and down streams levels indicated that there were no significant changes in beta amyloid levels.
1.2.2 Proposed adjustments / corrective actions :
As got early permission, we are focusing to explore other related mechanisms listed as cholinergic stimulation, encounter oxidative stress and control neuroinflammation.
1.2.3 Revised milestone completion date : ______(monthly)/______(year)
2.0 Significant achievement to date leading to meet project objective
(Please provide details on the project achievements, its status and prospects with regards to the followings :)
2.1 Intellectual Property Rights (Patent (patent application Filed / Granted, Overseas/Local), Industrial Design, Trademark, Copyright etc)
Nil
2.2 List of publications (Please attach with front page of each paper)
Three Conference Presentations:
1. Ciproxifan increases antioxidant activities while decreases oxidative stress in transgenic mice model of Alzheimer’s disease - The 2nd International Postgraduate Conference on Pharmaceutical Science, UiTM Puncak Alam, Malaysia.
2. Neuroprotective Effect of Ciproxifan on App(Sw) Transgenic Mouse Model - Pharmacology & Chemistry Colloquium 2014, UiTM Puncak Alam, Malaysia.
3. BACE-1 Inhibitory Activity and Neuroprotective Effect Of Ciproxifan Against β-Amyloid25-35-Induced Neurotoxicity In Neuroblastoma SK-N-SH Cells. The 3nd International Postgraduate Conference on Pharmaceutical Science, UiTM Puncak Alam, Malaysia.
2.3 Human Capital Development
No. / Name / Master/PhD / Title of the thesis / Start Date / Expected date of completion
1. / Ms. Siti Murnirah Jaafar / Master / Ciproxifan, a histamine H3 receptor Antagonist as a potential therapeutic Agent in Alzheimer’s disease / Sep 2012 / Sep 2014
2. / Ms. Nurol Eizzatie Binti Yaacob / Master / Protective effects of ciproxifan on experimentally induced dementia. / Mac 2014 / Aug 2016
2.4 Laboratory Proof of Concept (breakthrough / process /product) Please describes.
Date: 07-08-2015 / Signature:
3.0 Comment and Recommendation by RMC/ Institutional Research Coordinator/Committee
Date: / Signature:
Name: / Official Stamp:

Attachment:

1.1) Milestones description/ Summary of the Progress

Milestone Name / List of Research Activities / Completion Date (DD/MM/YY / % Completion / Deliverables
Planned Date / Actual Date
In vitro studies completed / 1.In vitro BACE- inhibition
2. Cell viability, neuroprotective and oxidative stress using Human neuroblastomacell (SK-N-SH)line against Aβ25-35 . / 05/2013 / 05/2013 / 100 / IC50 against BACE-1 is 500 μg/ml
Increased the cell viability, neuroprotective and oxidative stress against Aβ25-35 .
Genotyping of transgenic mice / 100 / Genotyping of transgenic mice revealed APP DNA sequence
Effect on memory models tested / Evaluation of memory using radial arm maze
/ 09/2013 / 09/2013 / 100 / Ciproxifan (3 mg/kg) enhanced spatial memory
Ciproxifan (3 mg/kg) reduced working memory error and reference memory error
Evaluation of APP and down streams / Evaluation of
Aβ1-40 and Aβ1-42 / 02/2014 / 02/ 2015 / 100 / Ciproxifan did not change the level of Aβ1-40 and Aβ1-42
Effect on cholinergic stimulation tested / Evaluation of acetylcholine and acetylcholinesterase levels / 100 / Ciproxifan enhanced acetylcholine level and reduced acetylcholinesterase activity.
Effect on oxidative and antioxidants tested / Evaluation of NO, MDA, catalase, SOD, GSH and GPx / 100 / Ciproxifan reduced NO and MDA , and increased catalase, SOD and GPx levels
Effect on neuro-inflammation / Evaluation of COX-1, COX-2, IL-1α, IL-1β, IL-6 and TGF-1β / 100 / Ciproxifan reduced COX-1, COX-2, IL-1α, IL-1β, IL-6, and increased TGF-1β
Beta- and gamma- secretase levels evaluated / Evaluation of beta- and gamma- secretase levels / 06/2014
(02/2015) / 06/2015 / 100 / Beta-secretase evaluation has completed and analyzing the results. Gamma –secretase is completed.
Immunohistological study / Amyloid plaques / 12/2014 (06/2015) / 06/2015 / 10 / On progress. The groups of animals have secured, waiting for ageing.
Project completion / 02/2015 (08/2015) / 08/2015 / 75 / -

Progress Report Science Fund