A shot in the arm for the Indian Drug discovery/Innovation ecosystem

The recent announcement of collaboration in the field of type 2 diabetes between Boehringer Ingelheim and Connexios LifeSciences, a Bangalore based drug discovery company is good news for the entire Indian ‘innovation’ ecosystem especially in the field of life sciences.

First, to the credit of the investors of Connexios (Nadathur Holdings and Investments), they invested in an idea and held on to it for a decade or so knowing well the pitfalls of such a ‘high risk high gain’ business model and at a time when such type of investments were unheard of in India . In India, unlike the West, we do not see many University spin offs working to bring breakthrough concepts/technology from the ‘bench to the bedside’ so in that aspect Connexios Life Sciences took a bold step to focus on System/Network biology approach to find novel targets and newer ‘first in class’ molecules. Another aspect that is interesting in this is that the company focused all its energies and expertise on type 2 diabetes and metabolic syndrome. Drug discovery is a costly and long drawn affair so focusing on one disease model was a good decision which led to concentrated efforts by the team. This also means that the company has more than one option in terms of novel targets and new small molecules to focus on the disease. So if one program fails, there would be a back up of other targets and small molecule entities (SMEs) giving credibility to the company.

The success of Connexios therefore gives a huge fillip to the ‘research based’ organizations. In India, very few companies focus on impactful research especially in the life science/biotech arena. As India is known as ‘the pharmacy of the world’, hence, most of the pharma companies devote their research activities on the development of generics (formulation, synthesis etc.) with very little emphasis on discovery of newer molecules or targets. This leaves a huge gap in the Indian innovation ecosystem. The news of the collaboration between Connexios and BI should also provide impetus to investors to believe in this type of Business model with more conviction than before. 

There is no denying fact, that India can become a major Innovation hub as it has a huge ‘talent’ pool of high skilled scientists who work at a fraction of cost as compared to the their western counterparts. The time has come to give more credit to our scientists and a better conducive research atmosphere with more investments in this sector so that we have more successful Connexios type stories in the future!

Effective diabetes treatment gets a nutraceutical pitch!

Type 2 Diabetes is a lifestyle disorder of an epic proportion. It is widely speculated that US, India and China are or are going to be the worst affected by this problem.

Current therapies focus on various strategies to control blood sugar but there is no cure at this stage. The older sulponylureas and metformins to the newer TZDs (thiazolidinediones), GLP-1 analogues and even SGLT2 inhibitors are vying to capture the diabetes market. The whole exercise is to promote medication that can control the HbA1c to controllable levels. 

Dietary extracts containing polyphenols, L-arginine etc. have been shown to have anti-diabetic potential. In a recent publication in the journal Endocrinology(Endocrinology August 19, 2013 en.2013-1529), it has been shown that dietery L-arginine can regulate glucose metabolism indirectly by inducing GLP-1 release in mice. Although the exact mechanism has not been dissected in the paper yet the authors suggest that G protein coupled receptor pathways might be involved. 

Since current strategies involve targeting the GLP-1 system by either inhibiting its rapid clearance by dipeptidyl-peptidase IV or using dipeptidyl-peptidase IV-resistant GLP-1 mimetics, it would be interesting to see development of novel approaches like dietary supplement with L-arginine and or L-arginine based therapies to enhance GLP-1 secretion from intestinal L cells. In essence, this study raises the possibility that nutritional-based strategies aiming to improve endogenous GLP-1 release may provide an alternative therapeutic approach to treat patients with metabolic disorder

Gut Microbiome – Type 2 diabetes association; outcome and possibilities

The phrase ‘my gut feeling’ has got another scientific validation with some new metagenomics studies published recently. After all, it seems that the gut can dictate the potential well being of an individual. A case in point is the latest paper in Nature journal in which the researchers conducted a gut metagenomic study on Chinese patients suffering from type 2 diabetes (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11450.html). Gut microbiome has been in the forefront of research especially after the advent of the Next Generation Sequencing technology. Today, the advancement in the field of development of sequencers and sequencing technology is even challenging the Moore’s law.

Gut microbiome also being called as the “other genome” or human’s “second genome” is implicated in many of the chronic diseases/disorders like obesity, inflammatory bowel disease and even depression so it is natural that with the latest technology in hand the scientists would focus on this in a much more refined manner. The present study finds some interesting facts about the commensals in the gut of Chinese patients suffering from type 2 diabetes. Functional characterization showed that there was a decrease in the level of bacterial chemotaxis, flagellar assembly, butyrate biosynthesis and metabolism of cofactors and vitamins in the gut bacteria of these patients. The researchers also found markers that indicated that the gut environment of a T2Dpatient is one that stimulates bacterial defence mechanisms against oxidative stress. This might be interesting as previous studies have implicated high oxidative stress levels to pre-disposition to type 2 diabetes. Strikingly, the researchers found orthologue markers that suggest that these diabetic patients might have a hostile gut environment. The researchers also found that there is moderate gut bacteria dysbiosis and an increase in several opportunistic pathogens.

The above mentioned salient outcomes of the study raise many exciting questions and possibilities. Does the change in gut microbiome composition a cause or an effect of the disease? Scientists would be addressing this part next with some studies in animals. Can in the future the gut microbiome sequencing be used as a predictive tool? Can modulating the gut microbiome cure such diseases? Can effective research in pro-biotics now fill in the space and fulfill what modern medicines could not achieve so far?

This is a perfect example of how a 21^st century technology has ignited a fresh look at the association of the microbiome with the human health