Consultation and Interaction at CSIR New Delhi with WHO-CIPIH Traditional Medicine Approach Bhushan Patwardhan, PhD Interdisciplinary School of Health Sciences University of Pune India
Just 26 NCEs in 2003 Average innovation deficit: 1.3 NCE/ year Increased Development time Safety and Efficacy remain challenging Failure at the end of pipeline Substantially increased development costs Innovation Deficit
Bioprospecting challenge Symptomatic therapeutics now aims at cause of disease. Earlier therapeutics: indirect, conjectural and coincidental, is now, direct and definitive based on intent. Combichem of Nature Major Discovery Engines are based on knowledge of little traditions. Great traditions are the true resources
Drug Discovery Approaches Ethnopharmacology Approach Serendipity and Synthetic Approach Chemical Biology Approach Genomics Approach Reverse Pharmacology Approach Systems Biology Approach Personalized Approach
Drug Discovery, Reverse Pharmacology and Ayurveda Field use Ayurvedic usage Standardize Whole formulations Experimental documentation (Observation) Ethnomedicines AYURVEDIC THERAPEUTICS Exploratory studies Standard extract Clinical trial Medicinal Plants Screening of extracts Isolation of active principles Experimental Research Clinical Phase II Herbal medicine Modern drug Therapeutics
Reverse Pharmacology: From Clinic to Laboratory Clinical wisdom National Consultations Team India Pharmacoepidemiology Bioprospecting Quality control methods Chemoprofile Herboprint Disease focus Pharmaceutics Pre-clinical Protocol development Stage I RCT Data consolidation Phase II and Phase III Pharmacodynamics
NMITLI Herbal Drug Development 3 Years Outcome Rheumatic and Musculoskeletal Disorders Osteoarthritis, Rheumatoid arthritis Stage I RCT indicated one formulation significantly better than Glucosamine Hepatic Disorders Pre-clinical suggest better activity than sylimarine Diabetes Pre-clinical suggest better insulin sensitizing activity
Leads from Ayurveda Curcumin, Gingerol, Gugullosterones, Eugenol, catechins, Anethol, Piperine, Apocynin, Genestein, polysaccaharides from TC, biflavanoids from Semecarpus, Gallates, Bacosides, Boswellic acid, Glycrrhizin, Allicin...
Curcuma longa Ayurvedic description Lead molecule: Curcumin Biological targets: Aryl hydrocarbon receptor, Cytochrome P450 enzymes, Glutathione S-transferase, kinases, COX, inos, MMP Therapeutic class: Cancer, Inflammation, Diabetes and Chemo prevention Chen HW.Anti-invasive gene expression profile of curcumin in lung adenocarcinoma based on a high throughput microarray analysis. Mol Pharmacol. 2004 Jan; 65(1): 99-110. Limtrakul P, Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids.bmc Cancer. 2004 Apr 17; 4(1): 13.
Zingiber officinale Ayurvedic description Lead molecule: Gingerols Biological targets: Vannolloid receptors Therapeutic class: Antipyretic, analgesic, antitussive, cardiotonic, and sedative Dedov VN. Gingerols: a novel class of vanilloid receptor (VR1) agonists. Br J Pharmacol. 2002 Nov; 137(6): 793-8. Ohizumi et al. Stimulation of sarcoplasmic reticulum Ca (2+)-ATPase by gingerol analogues. Biol Pharm Bull. 1996 Oct; 19(10): 1377-9.
Multiple Targets Need A Combo Bhallataka Guggulu Ginger Ashwagandha Nirgundi Guduchi Pipali Erand Pain, Cartilage Inflammation Oxidative stress Osteoporosis Anabolic CNS Immunomodulato Antistress Bioavailability Lubricant Activity Matrix: Systems-Biology Approach
Combinatorial, Holistic and Systems Approach: The Most Modern View The preparation of dual- or multiple-ligands on an almost rational basis is now conceivable and it can be expected that many of these molecules will yield drugs of superior clinical value compared with monotarget formulations. Multitargeted drugs: The end of the one-target-onedisease philosophy? Camille Wermuth, DDT 19, October 2004
Ayurveda: Systems Advantage Standardized traditional formulations for in-house use Science base Evidence to understand mechanisms Multi-prone Approach Drug Discovery engine to reduce Target to Lead bottleneck Chemical biology approach for new Leads Natural product extract libraries Holistic and Personalized Concepts
Traditions and Modernity: Future Medical Science Golden Triangle approach promotes effective integration of traditional wisdom, power of contemporary science & technology and the evidence base of modern medicine where the holistic strategies reflect from the systems biology principles. Golden Triangle approach provides holistic or whole person healing viewpoint besides a new platform for drug discovery. Mashelkar R.A., Chitrakoot Declaration, 2003
Thank You! With Dr. Ashok Vaidya and the CSIR NMITLI Team
Backup slides
Arthritis:Commonly used plants Bhallataka: Pain, Multi-targets? Erand:Cartilage? Lubricant Guggulu: Inflammation Ginger: Oxidative stress, Osteoporosis Ashwagandha: Anabolic, Adaptogen, CNS Nirgundi: Pain, Inflammation Guduchi: Antistress Pipali: Bioavailability
A comprehensive, interactive and AyuSoft intelligent software to assist Medical Practitioners and Researchers in Application of Basic Principles of Ayurveda
AyuSoft : Data Warehouse AyuSoft: Decision Support System Prakruti assessment, Disease Diagnostics, Diet & Lifestyle advice Encyclopedia PIMS Knowledge Database Drug Database Diet, Lifestyle Database Treatment Principles Disease Database Shaarir : Dosha, Dhatu, Mala
Classification of human population based on Ayurvedic concept of Prakruti : (n=76) Distribution of HLA alleles in Prakruti HLA Distribution in Kapha Prakruti DRB1 alleles 1 2 3 4 7 8 9 10 11 12 13 14 15 *11/13 HLA Distribution in Pitta Prakruti DRB1 alleles 1 2 3 4 7 8 9 10 11 12 13 14 15 *11/13 HLA Distribution in Vata Prakruti DRB1 alleles 1 2 3 4 7 8 9 10 11 12 13 14 15 *11/13 Cold Spring Harbor November 2004: Pharmacogenomics
Drug Discovery and Development Process Expensive, time consuming, numerous bottlenecks TARGET IDENTIFICATION LEAD IDENTIFICATION LEAD OPTMIZATION PRECLINICAL STUDIES CLINICAL TRIALS Economical, time sparing, least bottlenecks Reverse Pharmacology DRUG TO MARKET DRUG TO MARKET LARGE SCALE TRIALS RELEVANT SCIENCE DRUG DEVELOPMENT PRECLINICAL STUDIES CLINICAL TRIALS PHASE II & I
Other Efforts CSIR-TKDL, NMITLI Efforts Not just materials BUT the Systems Traditional wisdom has a message, logic and capturing intelligence from traditional information is important knowledge that needs protection AyuSoft project of MICT Thank you!