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In-Silico Designing

of Dopamine
Precursor for the
Treatment of
Parkinson’s Disease
Muhammad Ibrahim
L1F17BSBT0058
CONTENTS

01 02 03 04 05 06
METHODOLO
Background OBJECTIVES Rationale GY Outcomes Future Prospects
Background

 Parkinson’s disease (PD) remains one of the most common


neurodegenerative movement disorders.
 Caused over 6.2 million cases and 117,400 deaths around the world.
 Limited treatment options available.
 Restrained therapeutics
 Targeted DDS (Drug Delivery System) ‒ a new horizon.
 Little to no toxicity.
Objectives
1. To determine the prevalence
of Parkinson’s Disease
regionally

2. To identify target genetic regions for


therapy

3. To design a brain targeted ligand-


based DDS
Rationale
Levodopa (LD) used for more than 40 years in treatment of
PD. Long-term treatment with LD is, however, often
complicated by the development of various types of motor
response oscillations over the day, as well as drug-induced
dyskinesias.

Blood exosomes as potential DDS for delivery of dopamine as


the can pass through Blood Brain Barrier.

Nanoliposomes as drug delivery system. BPD along with


RVG29- and PEG-lip shows improved uptake instead of
free BPD.
METHODOLOGY
In-Silico Synthesis of
desired therapeutic In-Silic
Liposome. Synthesis of
(Using CMC Database)
dopamine
(Using PDB Bank,
precursor.
Uniprot, NCBI) Sequencing of
Target Gene dopamine precursor
identification (Using PCR)

Docking of both Dopamine


Precursor and Liposomes
DNA extraction with Ligand
and isolation. (Using Auto Dock Vina)
Outcomes

Liposomes proved
It is estimated that PARK1, PARK2 to be effective
about 65% of and PARK7 genes DDS due to
population showed were involved. binding of ligand
symptoms of with both
Parkinson’s dopamine
Disease. precursor and
liposomes.
Future Prospects

Possibility of
development of
treatment of PD.

Open door for Allow


the development implementing
of drugs that can these treatment
use liposomes as methods without
delivery system. the risk of
negative effect.
References
● Mengke Q, Qing L, Shanshan H, Luyao W, Yao F, Zhirong Z, Ling Z. (2018). A brain targeting functionalized liposomes of the
dopamine derivative N-3,4-bis (pivaloyloxy)-dopamine for treatment of Parkinson's disease. Journal of Controlled Release.
https://doi.org/10.1016/j.jconrel.2018.03.019

● Mengke Q, Qing L, Luyi H, Yao F, Luyao Wang, Shanshan H, Yu F, Shengyong Y, Zhirong Z, Ling Z, Xun S. (2018). Dopamine-
loaded blood exosome stargeted to brain for better treatment of Parkinson’s disease. Journal of Controlled Release. https://doi.org/
10.1016/j.jconrel.2018.08.035

● Khealani, B. A., & Baig, S. M. (2006). Clinical spectrum of Parkinson's disease from Pakistan. Singapore medical journal, 47(12),
1075–1079.

● The Parkinson Study Group. (2004). Levodopa and the Progression of Parkinson's Disease. New England Journal of Medicine.
351(24). 2498-2508. https://doi.org/10.1056/NEJMoa033447

● Haney, M. J., Klyachko, N. L., Zhao, Y., Gupta, R., Plotnikova, E. G., He, Z., Patel, T., Piroyan, A., Sokolsky, M., Kabanov, A. V.,
& Batrakova, E. V. (2015). Exosomes as drug delivery vehicles for Parkinson's disease therapy. Journal of controlled release :
official journal of the Controlled Release Society, 207, 18–30. https://doi.org/10.1016/j.jconrel.2015.03.033

● Cern, A., Barenholz, Y., Tropsha, A., & Goldblum, A. (2014). Computer-aided design of liposomal drugs: In silico prediction and
experimental validation of drug candidates for liposomal remote loading. Journal of controlled release : official journal of the
Controlled Release Society, 173, 125–131. https://doi.org/10.1016/j.jconrel.2013.10.029

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