Type 2 diabetes breakthrough

SL scientist discoverers highly effective drug for type 2 diabetes

The following is an interview with Dr. Wijayabandara. The transcript has been condensed and edited.

Q: Please talk about the discovery you have made

A: This discovery deals with the novel pharmacological property of a molecule known as beta-Amyrin acetate. I was able to isolate this molecule from the latex of a plant called Tabernaemontana dichotoma. The plant’s local name is divi kaduru. This was based on ethnomedical use of the latex of this particular plant, because the latex has been used for treating wounds.

I wanted to investigate the active substances present in this latex, so I succeeded in isolating and identifying the chemical molecules. I was able to isolate the molecule in Karachi at the International Center for Chemical and Biological Sciences in 2006. Once we isolated the compound, we were able to understand that this molecule could inhibit the enzyme called alpha-glucosidase, which is responsible for carbohydrate digestion in the gut. After figuring out the molecule’s structure, we got a good idea of its functions and we tested its ability to inhibit alpha-glucosidase in-vitro. We also did an animal study later on. We got very good results, as expected.

Beta-Amyrin acetate is 35 times more active than the standard drug, Acarbose, which is widely prescribed to treat type 2 diabetes. Our experimental findings were good and the molecule was tested on rats with good results. And then we wanted to file a US patent because we knew that this is a novel pharmacological property of this particular molecule. Then I submitted the application for a patent for this finding to the US Patent Authority in October 2006. I would also like to thank the former President and his Secretary for granting me support from the President’s Fund when I was at the Colombo University.

Q: How did you got the idea that the latex of this plant might hold novel pharmacological properties?

A: The idea came from the ethnomedical, or traditional uses of divi kaduru. This is one of the main approaches used in new drug discovery. We use different approaches, but an important one is seeing how medicinal plants are used and many important drugs have been discovered because of their traditional uses. There are many examples and this discovery is the same story.

Local people have used the latex of divi kaduru for many years to treat cuts. They apply the latex on wounds and believe that it has powerful antibacterial activity. That’s the basis. I also used the latex when I was young. We used the latex and I was curious to investigate the latex, especially to check its activity. I started out by analysing the plant’s antibacterial activity and I got very good results from this.

Afterwards I wanted to isolate the compounds responsible for the activity of this latex. That was the initial idea. But, because isolation and identification of molecules cannot be done here since we do not have the proper facilities in Sri Lanka, I had to go elsewhere to continue researching. I have established a collaborative research programme at the University of Karachi and I visited the university and did my own experiments using their facilities.

Q: Did you work with anyone else?

A: It was my own work, but there are two others on the patent. One is Muhammad Iqbal Choudhary, Director of the International Center for Chemical Sciences. The other is Shamsun Nahar Khan, from Bangladesh. He worked with me when he was a PhD student. Now he is a professor at a university in Bangladesh.

It was easy enough working in Pakistan, even though the country was having some problems while I was there. We worked inside the university and all the facilities for drug discovery were available under one roof. It was a nice atmosphere for advanced research.

Q: So what happened between 2006 and now? Why was there such a long delay?

A: Well, obtaining a U.S. patent is a very difficult task, especially for this kind of work. So there was a bit of a controversy due to comments from the patent examiners who argued that my discovery was not completely new. These examiners are tasked with doing a thorough search to make sure that the new patents are real novelties. There were no problems about the scientific investigation and the finding, but they were concerned about previous reports that showed this molecule in some other compositions. But they later cleared these issues and realized that the molecule did indeed have novel pharmacological properties. And, after all these activities, a patent was issued with some amendments to the claims.

Only recently did I come to know that this patent was issued. They did not tell me when they issued it and it has been backdated to 2008. Normally that’s what happens. Only last month I came to know, when I visited the U.S. patent website, that this had been issued. I do not know the exact date they approved the patent because it has been backdated. I could perhaps find out, though.

Q: Did you forget about it for around ten years?

A: Essentially, yes. There was a controversy and my team and I did not have any communication with the U.S. patent authority.

Q: What is the plan for beta-Amyrin acetate now?

A: Now we are working towards developing this molecule into a pharmaceutically elegant dosage form. We are now having discussions with various multinational drug companies because we are very keen to commercialize this innovation since it is so active compared to Acarbose. Type 2 diabetes is on the increase all over the world. It has become a real problem for the entire globe, as numbers are on the increase all over. We are looking at international companies because in Sri Lanka, drug development is not at a sufficiently advanced level.

Q: Will this drug change the fight against type 2 diabetes? Will it save many lives?

A: Yes, I think it will. We have completed the drug discovery phase and the next step is the drug development phase. The second phase will be easier because this particular molecule does not have bioavailability problems because the site of action is the gut. Also, this molecule could be synthesized because we know the chemical structure. Using the principles of organic chemistry, which is so advanced, we can make this compound.

Most drugs that were discovered from natural sources are currently synthesized in labs today. So beta-Amyrin acetate can be made on a large scale and easily supplied to the pharmaceutical industry. Our next goal is to get FDA approval in order to market this particular drug.

Now, there are different ways of treating type 2 diabetes. One of the mechanisms to control the disease is to inhibit the enzyme alpha-glucosidase, which is responsible for carbohydrate digestion. By inhibiting alpha-glucosidase, we can limit the increase in blood glucose level immediately after meals. That is the particular mechanism that beta-Amyrin acetate targets. As you know, diabetes cannot be cured, but what we can do is control it. It must be handled properly and one way of doing this is to control sugar levels in the blood. Also, because beta-Amyrin acetate is so active, we can reduce the necessary dose and this will in turn reduce the side effects people have. Scientists are constantly looking for more effective drugs to solve the problems associated with currently used drugs. With this particular drug, you can take it orally, because the site of absorption is the gut. I should also add that those with type 2 diabetes should take the drug before each meal.