Diabetes cure - a fresh approach is the need of the hour

We are in the 21^st century. A new millennium and a hope that new discoveries, innovations would help us thwart diseases like cancer, diabetes, schizophrenia etc. Actually, if we leave the mental illness aside for a minute as the science studying mind/brain is pretty nascent; then one would ponder why we are still years if not decades away from finding a credible cure for diseases like cancer, diabetes and HIV! Right now we only treat diseases like diabetes not cure them………………….

Let’s talk about diabetes, type 2 to be precise for a moment. The best medicine for decades to treat (not cure, mind it!) has been metformin. This humble drug has shown tremendous resilience in terms of safety and efficacy and is and probably would be the first line of therapy for years to come!

 The current or upcoming therapies for diabetes mostly revolve around two aspects – a) increasing insulin secretion (sulphonylureas take the cake here) or b) increasing insulin sensitivity (PPARs/metformin etc). Even the new ones like the GLP-1s or DPP-IV inhibitors ultimately increase insulin secretion though independent of glucose concentration (better than sulphonylureas!). But to me these are just like “cosmetic” drugs treating the symptom not the cause and I feel that we have still not properly understood this disease. In this context, I would like to share a new discovery that can change the perception of how we look at type 2 diabetes.  New research has suggested that the development of insulin resistance and type 2 diabetes may be linked to an immune system reaction gone awry. Till now, we have been looking at type 2 diabetes as a metabolic disease and immune system malaise is mostly associated with the other cousin of diabetes , the type 1 diabetes. Now, if the above said observation is indeed found to be credible in subsequent research then it would mean a tremendous paradigm shift in type 2 diabetes research. I guess, this kind of observation/research is the step in the right direction to understand the cause of the disease.

Probably, joining the pieces of the diabetes puzzle through innovative and fresh thinking is the right approach to finding a “cure” for this scourge rather than trying to better the current therapies to “treat” the disease.

Indian Pharma - Generic all the way and innovation out of the way?

India is poising itself to be the new Knowledge superpower. An economy which is dubbed as a knowledge economy with huge asset of English speaking educated people who can take India to the top. However, why is it then that we do not hear or read about any “new” path-breaking drug development from India? We have an estimated close to 20,000 pharma companies employing the “best” scientists/researchers/chemists etc.  In fact last few years have seen a “reverse brain drain” giving India back its lost scientists and researchers. So what pulls us back from innovating?

Well, there are many reasons behind it. But one of the most important reasons is the focus on generics rather than “innovative” research in the Indian pharma industry. It is easy for a pharma company to achieve a better return of investment with very little risk if they invest in generics. Big names like Ranbaxy labs which were into some good “research” completely re-focused themselves into generics business. Most big companies in India spend a penny on innovative research as compared to their western counterparts. This trend, though profitable for pharma may be disastrous for them in the long run and also for the country.

Drug discovery is a 'high risk and high return' business. But most small and medium level pharma being run by business families probably do not understand the importance of innovation. For most, it is how much do they get in return and how fast?!!!! I know of instances when reputed pharma companies recruiting scientists would ask questions like “can you develop XYZ in one year?” or “what do we gain from your academic experience, would it help us get our investment back?”  Questions like these not only show the hollowness of approach but also affect the morale of budding scientists as they also start to think everything in terms of investment and returns without actually thinking about innovation.  I am not in the favor of giving a lifetime deadline or a free run to scientists as well (as happens in most of our Government labs) but want to see a rational approach.

Moreover, unfortunately, we do not yet have the “Venture capital” mindset in drug discovery. Indian Venture capitalists are gung ho about investing in IT but see black when approached for investment in life sciences!!! There are few Indian companies that are trying to change that but they are constantly under undue pressure from their investors, who would have seen other IT start ups booming by the time a biotech/pharma drug discovery start up barely starts walking!!!!!!

In conclusion, penny wise pound foolish approach of Indian pharma industry would be detrimental for the overall growth of this sector in the long run if the mindset and approach is not overhauled!  

Novel drugs and pharma industry - a catch 22 situation

Success has many fathers and failure has none! Well, this adage is true in every aspect and surely holds water in pharma industry too. Whenever a new mechanism of action (MoA) of a drug shows promise, pharma companies bring their own version into their pipeline to be either “first in class” or be the “best in class”in that segment. But here is the catch. Not many of the new potential class of drugs (MoAs) have been studied carefully for a long period of time (~10 years or so) and hence scientific community as a whole would be in the dark to know what would happen if such drugs are in chronic use for a long period of time!

So, it is strange indeed, a kind of catch 22 situation. We need new drugs to counter diseases or disorders but we probably cannot wait to see the safety of these drugs for a decade to deem them fit for consumption! There have been many occasions when blockbuster drugs have been withdrawn after some time from the market when side effects were found to be profound. This leads to huge financial loss for the company involved and trust deficit not only in the company but also in the regulatory bodies which approve them in the first place. Of course, the loss of human lives or debilitating diseases associated in such cases cannot be weighed in terms of financial loss.

It is not that everything (I mean the potential side effects) cannot be predicted beforehand. We have seen that even when drugs in the pre-clinical stage have shown some glaring side effects yet these have been approved. Worse still, pharma companies sometimes hide such data on the garb of statistics and get around the approval door. But in the long run this leads to loss for such companies only!

Nothing in this world is full of positives and devoid of risks and so is the business of drug discovery. But what we need is rational understanding of novel MoAs and honesty before the pharma companies release their drugs into the market for human consumption.

Research in Pharma and Government labs - a short sighted approach and greed

Is lifelong chronic therapy for diabetes or other metabolic disorders bane or boon? Well, it depends on which side you are on. For big pharma it is a boon but for patients I would say it is not so good an omen. That brings me to a fundamental question. Are big pharma companies deliberately not being able to find “cure” for such diseases?  Modern science has evolved a lot especially during the last few decades. We are at the realm of finding evidence for dark matter or other theoretical subatomic particles but  we are still far from understanding the how a normal cell functions! There are still some unexplored territory as far as understanding the working of a cell is concerned; forget about human disease or disorders.  So it is not a co-incidence that modern science has yet to provide “cure” for most of the diseases although we have been on the winning side in taking head on some infectious diseases (thanks to antibiotics)!

So, what is the way out? Well, the answer is not that simple. We ought to give rightful importance to basic and applied research equally.  But here comes the negative part. Research means lot of money and it is foolish to leave all basic research on Governments’ shoulders. The Big pharma ought to put in more money into research. I know of many instances where in big pharma companies have good and interesting data generated, but they do not divulge that fearing competition or deem the information useless in terms of financial benefit. Ultimately, this leads to lot of repetitive research and that means lot of money! So ultimately it is the loss to the public. Also, recently many pharma companies have moved out of  research in some disease areas  and that leads to a lot of void; a negative approach of pharma on research in new antibiotics is just a point in case.

Even Government funded labs are poor in their approach towards research. Lot of public money is wasted in the name of basic research.  I think time has come to delve deeper into our conscience as scientists/policy makers in government and in the private sector. Let us work in a collaborative way to understand disease and disorders , otherwise we would have no one but our ‘greed’ to blame

Diabetes and dyslipidemia

ok folks, so now we would be discussing some basics and pathology of type 2 diabetes

Well, to start with let us understand what happens in the disease. We all know that in type 2 diabetes, the body's ability to utilize glucose with the aid of insulin goes down dramatically!!

This is sometimes called as "insulin resistance" which is a precursor to the full blown type 2 diabetes. When this condition sets its foot our humble pancreas start to pump more insulin to let the glucose seep in to the various tissues especially muscles and adipose. Interestingly, in diabetics another disastrous event takes place. The 'great' liver has this property of producing glucose, the process is known as "gluconeogenesis". This process normally occurs when the body perceives a need for glucose and probably when it is in the starving mode! however even though there is enough glucose flowing in the system of diabetics the liver starts producing glucose and releases it in the blood thus raising its level further!!!

So as we can see there are multiple problems here and everything is leading to increase in blood sugar!!!! At the same same time research has shown that there is an increase in fatty acid level as well in the system (triglycerides etc.). This increase in sugar and fatty acids has a detrimental effect on the pancreas. We have seen and it is also known that such an insult to the pancreas leads to the death of beta cells (chief insulin producing cells)

So folks as one can see the key to avoid or delay the progression of the disease is to 'somehow' do away with insulin resistance! and as mentioned in my previous blog nothing is as effective as exercise or yoga.

 Both Yoga and exercise have been shown to increase glucose uptake and there is a view based on research that exercise activates a pathway called AMPK (5' AMP-activated protein kinase) which incidentally has been shown to be activated by a class of widely used drug for treating this disease called metformin!

 In all, it is suffice to say that to be diabetes free it is imperative to have physical activity on a daily basis!

Type 2 diabetes is a man made disorder. Lifestyle/ environmental changes are slowly generating a monster in our midst and we are not even aware of it!

Rather than popping a pill to manage the disease our emphasis should be to first look at the natural available resources like yoga, exercise and increased fruit/vegetable intake.

Another very important issue is stress management. We know that high level of cortisol or the stress hormone causes insulin resistance so it is understandable that prolonged stress conditions in work or in our social set up is a major ingredient for triggering this disease. Though we also know that some people are predisposed to this disease (in other words are genetically inclined), we can surely try and delay the onset by following a healthy lifestyle. 

Now whatever I have written so far is well known and is not new to many but this is just a prelude to my subsequent blogs that would discuss the available therapies and the pitfalls associated with them.

Till then lead a healthy life and have a great life!