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12 November 2013

Mining the Amazon for drug candidates: choosing the right tools for the task

Ethnobotanical research could play a key role in the scientific development of Latin America.

 

The Amazon is a biodiversity hotspot from which modern medicine has a lot to learn. Beyond the plethora of therapeutic compounds awaiting discovery, the indigenous communities living within the Amazon have a wealth of traditional medicine to share. But how will the modern pharmaceutical industry undertake this daunting challenge?

Plants represent a virtually untouched reservoir of novel drugs.1 On average, it takes 10 to 15 years for a single drug to become clinically available.1 Between 5,000 to 10,000 compounds are screened before a single drug makes it to the market. Of the successfully developed drugs, approximately 60% have a natural origin, either as modified or unmodified drug entities, or as a model for synthetic drugs.

Surprisingly, it is estimated that only 5-15% of the approximately 250,000 to 750,000 species of higher plants have been systematically screened for bioactive compounds. Further studies to develop more drugs of natural origin have been limited due to their structural complexity, high extraction cost, and apparent lack of pharmacological activity. However, the application of reverse pharmacology concepts – from traditional use to the laboratory2 – may help to standardize the screening of plant extracts and effectively identify potential bioactive compounds.

What can we learn from the practice of traditional medicine in Central and South America?

Traditional forms of medicinal treatment are used today by a large percentage of the world population, especially in developing countries. Traditional medicine is important in Central and South American countries where national health systems are limited and the difficult economic situation prevents access to standard medicine for the majority of the population.3

In particular, standardized and accessible herbal medicine may be useful in the treatment and control of neglected tropical diseases4 (NTDs) as a therapeutic alternative in remote areas.5 Moreover, knowledge of traditional medicine may help identify new chemical compounds to add to the drug development pipeline.6,7 The impact of traditional medicine is not limited to developing countries. Indeed, some areas in North America with large populations of Latinos or Native Americans, or in regions close to the Mexican border, keep some of these traditions as well.8

Megadiversity in Ecuador

 

Located in the tropical Andes-Amazonia transition zone, Ecuador is considered one of the countries with the highest biodiversity in the world – one of five ‘megadiverse hotspots’.9 Approximately 30% of its population belongs to different indigenous groups still practicing and relying on traditional medicine3. Nevertheless, research in the area of ethnobotany in Ecuador is scarce.10-15 Studies presenting any pharmacological evidence to support ethnobotanical use of plants are practically nonexistent. Hence, the potential for drug discovery and development in Ecuador is substantial and requires well-designed systems pharmacology strategies.

Ethnobotanical research could play a key role in the scientific development of Latin America.

Pharmacometric methods are needed to elucidate the clinical pharmacology of botanical drugs. This means using robust mathematical and statistical techniques to study the origin, function, kinetics and toxicology of drug candidates.

These are important components of model-based drug development (MBDD). Understanding the dose-concentration-response relationship will be fundamental to thorough ethnobotanical research in developing countries16, in particular for infectious diseases.17

Many of the current agents used to treat malaria, tuberculosis, and HIV were developed before modern methods of drug discovery and lack reliable dose-concentration-response data.17 In addition, combination therapy is routinely used in many areas of infectious diseases to prevent resistance to treatment.

Ethnobotanical research that relies on pharmacometric techniques will contribute to our understanding of public and global health issues and play a role in the economic and scientific development of Latin American countries while contributing to the preservation of cultural knowledge and biological diversity.

More at Karina’s blog: here.

References

1. Khosla C, Keasling JD. Metabolic engineering for drug discovery and development. Nature reviews. Drug discovery. Dec 2003;2(12):1019-1025.

2. Patwardhan B, Mashelkar RA. Traditional medicine-inspired approaches to drug discovery: can Ayurveda show the way forward? Drug discovery today. Aug 2009;14(15-16):804-811.

3. Tene V, Malagon O, Finzi PV, Vidari G, Armijos C, Zaragoza T. An ethnobotanical survey of medicinal plants used in Loja and Zamora-Chinchipe, Ecuador. Journal of ethnopharmacology. Apr 20 2007;111(1):63-81.

4. Sustaining the drive to overcome the global impact of neglected tropical diseases: second WHO report on neglected tropical diseases. World Health Organization;2013.

5. Cocquyt K, Cos P, Herdewijn P, Maes L, Van den Steen PE, Laekeman G. Ajuga remota Benth.: from ethnopharmacology to phytomedical perspective in the treatment of malaria. Phytomedicine : international journal of phytotherapy and phytopharmacology. Nov 15 2011;18(14):1229-1237.

6. Hefferon K. Plant-derived pharmaceuticals for the developing world. Biotechnology journal. Jul 15 2013.

7. Koff WC, Burton DR, Johnson PR, et al. Accelerating next-generation vaccine development for global disease prevention. Science. May 31 2013;340(6136):1232910.

8. McNeill BW, Cervantes J. Latina/o Healing Traditions: Mestizo and Indigenous Perspectives. . Routledge; In press.

9. Richter M, Diertl KH, Emck P, Peters T, Beck E. Reasons for an outstanding plant diversity in the tropical Andes of Southern Ecuador. Landscape Online. 2009;12:1-35.

10. Béjar E, Bussmann RW, Roa C, Sharon D. Medicinal Herbs of Southern Ecuador. Spring Valley: Latino Herbal Press; 2002.

11. Bussmann RW, Sharon D. Traditional medicinal plant use in Loja province, Southern Ecuador. Journal of ethnobiology and ethnomedicine. 2006;2:44.

12. Cerón C, Montalvo C. Etnobotánica de los Huaorani de Quehueiri-ono Napo-Ecuador. Quito: Abya-Yala; 1998.

13. Iglesias G. Sacha Jambi. El uso de las plantas en la medicina tradicional de los Quichuas del Napo. Quito: Abya-Yala; 2002.

14. Naranjo P, Crespo A. Etnomedicina, Progresos Italo-Latinoamericanos. Vol I. Quito: Abya-Yala; 1997.

15. Naranjo P, Escaleras R. La medicina tradicional en el Ecuador. Quito: Corporación Editora Nacional; 1995.

16. Pillai G, Davies G, Denti P, et al. Pharmacometrics: opportunity for reducing disease burden in the developing world: the case of Africa. CPT: pharmacometrics & systems pharmacology. 2013;2:e69.

17. Davies GR, Hope W, Khoo S. Opinion: the pharmacometrics of infectious disease. CPT: pharmacometrics & systems pharmacology. 2013;2:e70.

Photo: Sara y tzunky and Argonne National Lab via Flickr.