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What is the Future for Drug Discovery?

What is the Future for Drug Discovery

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The future for drug discovery is dark grey. Big Pharma as we know it is going to to die. Only a few brave companies will survive, but only after a painful adaptation to the new reality.

Some are trying to adapt, hoping their pink hammer will fix the situation.

My concern has hit a maximum after reading this article by Simon Campbell (ex-Pfizer)  What is the Future for Drug Discovery in the UK? In it he describes the roadmap pharma industry should follow in order to survive. Some of the ideas are frightening.

 

A new and sustainable funding model with public sector participation is urgently required for world class UK scientists to invent and develop innovative medicines that meet the medical needs of the 21st Century.

Public money is needed, but the profits will go for the companies, I guess. Does it sound like what happened with banks all over Europe?

We should build a consensus of expert stakeholders with the common objective of informing and influencing future development of world class healthcare innovation in the UK.

Lobbying and creating brain washed scientists is not the most ethical way to create a new future for drug discovery.

The government has stated a firm commitment to life sciences as a catalyst for growth, but emphasis appears to be on clinical trials, biologics and cell therapies rather than on cost effective and orally delivered small molecules that are the bedrock of any healthcare system.

More lobbying. What if “orally delivered small molecules” can’t solve every single disease? Why not to look a bit further from our belly button? What happened to personalized medicine? Prevention? Promoting a healthy life style?

Future R&D should focus on therapeutic areas of significant medical need where transformative new drugs will improve quality of life, and bring economic benefit.

No long tail business in the future for drug discovery, only focus on what makes big bucks.

We must address attrition […] expand pre-competitive collaborations between industry/academia to focus on target selection/validation, predictive toxicology and to identify patient sub-groups that respond to agents with novel mechanisms of action…

This sounds a bit better. Collaborating with academia and targeting certain subgroups of patients.

…These initiatives would reduce risk, simplify clinical trails and lower costs

Ah my friend! We thought they want to target on sub-groups to improve the quality of their products, but it was just to reduce costs and maximize benefits. Stupid me, for a moment I forgot they are here for the money.

A network of Therapeutic Centres of Excellence should be established […] expert medicinal chemists released by industry […] Unused assets from Pharma could be included.

Experienced industrial scientists should be also embedded in world class biomedical centres by creating new chairs in medicinal chemistry

So these released experts working in Centres of Excellence created by Pharma are going to continue to use pharm.’s ideas to push pharm.’s agenda? Or on the other hand are going to push patients’ agenda?

If world class Pharma/Biotech talent is allowed to fade away, it will be extremely difficult to re-build quality in the future.

Many times something has to die so a better version can be born. It can be difficult, like many profound changes, but at the end of the process it will pay off.

Reallocation of current budgets…

Government, Funding Councils and Charities should now invest for future growth, as economic benefits will largely depend on a strong UK drug discovery capability that invents new medicines for world wide commercialisation

Some old school Fear, Uncertainty, Doubt (FUD) to end with. If you don’t give pharma big public bucks we are all screwed. It is again the same situation with banks, they take risks and when in trouble, public money has to be given. This only creates the incentives to be stupid again, since public institutions will take care of you no matter what.

 

If your only tool is a hammer, everything looks like a nail.

“Orally delivered small molecules” is the hammer that pharmaceutical companies have been using for decades. They have realized they only have a hammer. Unfortunately, they are asking public money to paint it pink and try to fix problems now with a pink hammer.

What Is Metabolomics?

What Is MetabolomicsYou might have heard that some scientists sequenced the human genome and this would bring the cure to many diseases.

Sorry to disappoint you but in biology and health there is much more than meets the eye.

Your genetic heritage might indicate that your have more chances than usual of developing a disease, but there are many other factors that will contribute to this finally occuring.

Metabolomics studies the footprint of these factors in order to give a more accurate picture of your condition.

In this post you will find what is metabolomics explained in simple words and with examples of application areas.

Metabolomics in simple words

Metabolomics surveys the metabolites that are present in organisms.

What are metabolites?

Metabolites are small molecules, smaller than genes or proteins. They are involved in metabolism as intermediates or products of metabolic processes.

Human examples of metabolites are hormones, amino acids, lipids, vitamins, and antioxidants, among others. Not only humans have metabolites, in fact all live beings need metabolites for their functioning.

Metabolites are responsible for the taste of tomatoes, the smell of plants, the color of fishes, and the poison of spiders.

Why is metabolomics useful?

Metabolomics describes the phenotype of an organism, which quoting Wikipedia is:

the composite of an organism’s observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, phenology, behavior, and products of behavior (such as a bird’s nest).

Phenotypes result from the expression of an organism’s genes as well as the influence of environmental factors and the interactions between the two.

The presence or absence of metabolites (and their concentrations) describes the state of an organism.

A practical application of this definition: Metabolomics can also describe the metabolic signatures of disease versus normality.

Imagine two identical twin brothers (who share almost identical genes). One has a stroke at 45 while the other lives healthy till he dies at 90. How can this happen if they are almost identical? Easy, lifestyle.

Can you guess who was having 2 meals a day at McRonald’s?

If you would have used metabolomics to check their lipid profile, you would have seen that the one with the stroke had a LDL cholesterol level abnormally high.

Grape tomatoes.

Examples Of Metabolomics Research

Metabolomics has proved useful to answer biological questions, for instance to determine the effect of a clinical intervention (aka, if I do this to these people, what do I see?) or to unravel the mechanisms of disease, to name a few.

If you are wondering what is metabolomics doing in the real world and what kind of biological questions metabolomics can answer, check these two examples.

How can I make my tomatoes tastier?

Imagine a company that sells tomato seeds want to improve their tomatoes in terms of taste, texture, aroma, and other properties you could not imagine a tomato possess.

Here the company can have two options, either modify genetically the tomatoes or to cross different breeds.

Next, a panel of tomato tasters (you guessed it, taster like with wine) give scores for these properties of each tomato sample.

Now, remember that metabolites are responsible for the taste and other properties of tomatoes.

By comparing the metabolic profiles of tomato types that scored high and low in each property, one can discover which metabolites contribute positively and negatively to the quality of tomatoes.

Is this diet good for reducing cholesterol?

Since you are interested in nutrition and health, you are curious about which diet improves your cholesterol, this is, bad cholesterol goes down, good cholesterol goes up.

The study is designed as follows: 4 different diets plus an extra control diet are chosen. You select 5 groups of people and each one gets a diet.

After some weeks, blood samples from the participants are collected and measured to determine the concentration of different cholesterol metabolites. And there you have your ideal diet to improve you cholesterol levels.

Sounds simple, huh? In fact, this kind of research, if you want solid results, requires a joint effort of many research centers and hundreds of participants.

Check this research about the best diet for  weight-loss maintenance.

Their goal was to decide which combination of high/low protein and high/low glycemic index was the, so you avoid the “rebound effect” (spoiler alert: the best diet is high protein and low GI).

 

Microfluidic devices

Future Directions Of Metabolomics

Single Cell Metabolomics

Two individuals have different metabolic profiles if we measure their urine or blood. In the same fashion, different cell types in our body have different profiles.

In a not-so-far future, we will be able to extract a tiny sample from a single liver cell and compare its metabolic profile to the profile of a white blood cell, for instance.

By doing so, we will be able to focus on the specific organ or tissue involved in our research.

Metabolomics For Personalized Health

Have you heard of what 23andme.com is doing with gene analysis? you spit in a tube, send it by post and you get a detailed report on your genetic predisposition for a long list of diseases.

Now imagine the same, maybe instead of saliva samples with urine, but you will get a metabolic report, which describes your current health and if you are in any developmental stage of a disease.

 

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