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DDD spoke with Andrew Dahl, CEO of ZIVO, to learn more about the potential of phamacognosy.

1. What is the historical precedent for using pharmacognosy, the search in nature for potentially useful compounds, as a tool for drug discovery? 

It Is the oldest form of pharmacology. The Ancient Babylonians, Chinese, Indians and Egyptians created remedies from herbs, fruits and minerals. Aspirin was derived from the leaves of a willow tree in Northern Europe.

2. As the development pipeline in the pharmaceutical industry runs progressively thinner, why is it worthwhile for companies to look to the world of nature, and plants in particular, to develop new drug candidates? 

The current drug development paradigm is best described as testing random combinations of molecules with high-throughput screening protocols to find bioactivity of any kind. It is time-consuming and very expensive, with no guarantee of success. Therefore, pharmacognosy is getting a second look because the link between a natural product and a disease model has already been established. But the task of elucidating the bioactive compound(s) from that natural product, which can be quite elusive, is not for the faint of heart or lack of deep pockets.

3. What are some of the characteristics of the biologically active compounds produced by microalgae that make them especially appealing as a potential source for drug discovery? 

Algae produce an abundance of sterols, steroids, phenols, ecosanoids, peptides, proteins, polysaccharides and lipids that are biologically active in mammals. Some marine algae are being cultivated as source material for cancer drugs, while others provide cardiovascular benefits, such as Omega 3 oils, but without the residual mercury that may be present when extracting Omega 3 oils from fish or crustaceans.

4. Why could a partnership between a pharmaceutical company and a R&D company focused on algae be beneficial? 

The bioactive compounds produced by a single algal species can number in the hundreds. Once the species is understood and its metabolism mapped out, a biotech firm is in a position to deliver a stream of useful lead compounds or discovery-stage candidates at relatively low cost and timelines.

5. What kinds of therapeutics could be targeted by algae-based compounds? 

Our research into a single strain has revealed potential therapeutic applications for bovine mastitis, canine osteoarthritis and human cholesterol management. There are hundreds of researchers around the world expanding the universe of applications for both humans and animals.

6. Have any algae-based compounds been developed and/or commercialized to date? If so, which ones? If not, what developments in this area are currently furthest along? 

Alginates and glycoaminoglycans are already in common use in pharmaceutical manufacturing. Compounds such as fucoidans and ulvans are in the process of commercialization. Dr. William Gerwick at the Scripps Institute/Skaggs School of Pharmacology at UC San Diego is a pioneer in identifying potential cancer treatments that originated in marine algae.

7. How can the emerging field of glycoscience benefit from the incorporation of algae into drug development programs? 

Algae produce an amazing array of sugars, from simple oligosaccharides to complex, multi-branched polysaccharides with double and triple carbon bonds, some

of which are naturally sulfated or methylated, effectively supercharging their potency. The role of sugars in complex metabolic processes is only now being discovered. Many protein-to-protein binding reactions have been found to be mediated by a strand of sugar. Like antibodies or hormonal therapies, glycoscience will likely have a significant impact in our understanding of mammalian metabolism and how we address disease, injury or dysfunction.

8. What are the principal challenges involved in adapting algae-based extracts for pharmaceutical compounds?   

Complexity, fragility and sheer volume of potential combinations. Finding a bioactive is complicated by the fact that in attempting to isolate and analyze it, the bioactive itself is transformed and the bioactivity is lost or substantially altered. This is not limited to algae. Many natural products present a significant challenge to identification and characterization of a single effective agent.

9. What core message(s) should be conveyed to pharmaceutical companies that are considering incorporating algae-based compounds into future drug candidates? 

I don’t think that pharma companies look at it that way They are generally skeptical of bioactives derived from natural products because those bioactives can be costly or complicated to manufacture at scale, and/or consist of a heterogeneous mix of actives that is not consistent in its beneficial effects, or is not stable over time.

10. How difficult is it to initially separate the bioactive from the non-bioactive molecules from algae in quantities that are usable for subsequent processing by the pharmaceutical industry? 

Depends entirely on the structure and chemical composition of the bioactive agent. If it’s a small molecular entity like a flavonol, it’s relatively straightforward. If it’s a huge polysaccharide with multiple branches and double bonds, it’s probably impossible.

11. What specific research results to date have seemed to be most promising in suggesting a bright future in studying algae as an avenue for drug discovery? 

University of Ireland – Galway is a center for algal research, as is the Kaoshang Marine University in Taiwan. Everyone in this field tends to their own R&D, so we can’t comment on algae research in general.

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