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30 years from now: what will clinical researches look like? Rustam Gilfanov’s opinion

An effort to look into the future and find out how quickly new drugs can be developed.

These days, it takes from 8 to 14 years to do preclinical and clinical trials before medicines appear on the shelves of drugstores for the first time. Besides, it costs at least 1.3-2 billion dollars to test a new compound. 80% of overall expenses are preclinical studies and clinical trials. Moreover, according to statistical evidence, only one out of five compounds reaching Phase I of trials will subsequently be approved.

How can this process be facilitated, and how can we save money? This article is an attempt to make a prediction of what clinical trials will be in 30 years.

The models crisis

It still takes a lot of time and money to develop a drug, and the probability of success is still low. According to scientists’ estimation, average investments in this area of research are 1.3 billion dollars per drug, while the approximate time of development ranges between 5.9-7.2 and 13.1 years for non-oncology and oncology medications, respectively.

Only five out of 5,000 compounds reaching preclinical studies make it to Phase I of clinical trials. The general approval rate of trialed drugs is not more than 13.8%. The main reasons for clinical trial failures are toxicity and low efficiency.

Those failures often happen because of poor choice of models: compounds that displayed great potential during animal tests happen to be inefficient when used in relation to people. This is the reason why one of the main trends of today’s drug development is to deeply analyze the level of the model adequacy when it is used for preclinical research (regardless of what it is: a rat or a macaque) as compared to the human body.

In spite of the fact that most failed drug candidates are inefficient but harmless, the selection of irrelevant models may sometimes cause disastrous effects. For example, the case with the TeGenero company. It was working on a new medicine against autoimmune disorders. TGN1412 (Theralizumab), a humanized monoclonal antibody, showed wonderful results during the preclinical trials when used on monkeys. Although, human volunteers who participated in Phase I trials suffered a lot from a severe cytokine storm an hour after administering the test drug. More than that, some participants even went into a coma.

The incident was caused by a simple reason: it happened that safe TGN1412 dosages for monkeys and people are entirely different. At the same time, this proves that animals can be only provisional prototypes of a human body.

As for the effectiveness of new medicines, drugs against cancers and CNS disorders take the longest time before being introduced to the market. According to statistics, they comprise half of all failed clinical trials. Two factors: the complexity of the diseases and the multiple points that have an impact on their progression make animal tests of new medicines almost meaningless.

3D models and organs-on-a-chip

One of the ways to fill in the gap between human beings and animals is to use three-dimensional models of human organs that efficiently recreate the states of a human body due to the environment of neighboring cells and the extracellular matrix.

For example, 3D models help to evaluate a more accurate dosage during cancer drug trials. External cells obtain a higher dose than those within the culture, like cells in a living body (especially in the case of solid tumors).

At the same time, 3D models cost a lot and are difficult to design and use. That is why, in spite of their functional benefits, they are not as popular among researchers as two-dimensional versions. However, they might become commonplace three decades from now.

Organs-on-a-chip (OOCs) is a more sophisticated model. The devices cultivating cell cultures, simulating mechanical and physiological responses of organs and even organ systems, can combine a 3D organ model with a microfluidic platform. Researchers have already made up the OOC models of microvessels, kidneys, lungs, liver, intestine, and their combinations.

How can such a model be created? For instance, preparing a 3D culture for modeling bronchi and smaller airway tissues demands primary bronchial human cells. The cells are cultivated in culture flasks and then seeded on platforms with porous membranes that make it possible to place them at the air-liquid interface and differentiate the original basal cells of the bronchial epithelium.

Actually, the concept of organs-on-a-chip occurred for the first time a decade ago. However, it did not become widespread because of its complexity and the strict legal regulations that were imposed on the pharmaceutical market.

At the same time, some companies help Big Pharma to reduce their costs and decrease the risks of unsuccessful trials by suggesting OOC solutions. For instance, the Emulate startup is a partner of several pharmaceutical companies that design chips studying immune responses to CNS disorders. The company also developed the liver-on-a-chip model for analyzing microbiome effects and carries out toxicological research when developing the drug.

The chips can deliver the data previously obtained through animal or human tests. This technology has the potential to revolutionize the industry and entirely refusing preclinical trials involving animals. In the best-case scenario, researchers will make a presentation of the “human-on-a-chip” model in 30 years and introduce individualized preclinical studies.

Omics data when designing a drug

Some points associated with preclinical trials can be resolved by omics data which are vast pools of molecules (they are collected on various levels of biological processes). These molecules demonstrate the state of a whole body or its part. Omics data are analyzed by bioinformatics which is an interdisciplinary area combining statistics, biology, and computer science.

Omics data are mainly applied at the earliest phases of preclinical trials to estimate the features of candidate molecules by using the information obtained from cells and to get a “mold” of a sick organism for testing the influence of various substances.

A classic situation of the same-level omics data use involves the comparison of tissue transcriptomes of healthy and diseased people. Researchers study the expressions of the gene for determining damaged molecular pathways. Afterwards, they choose the candidate molecules that can have an impact on the target molecules.

The latest trend involves the analysis of multi-omics data, i.e., the information on peptides, metabolites, proteins, and RNA and DNA sequences. This assists in seeing the entire picture of a disease, because pathological processes have a negative impact on multiple cell levels.

Ideally, it will become a standard practice 30 years from now to collect various data arrays at the start of preclinical studies to identify disease progression patterns, determine and test potential targets, choose and check candidates, and leave out toxic molecules. This is sure to make drug design much quicker and more individualized.

Moreover, it will make it possible to control the entire process (except for animal tests or cell modeling) via a computer. Provided the fact that expressions of some disorders have already been published, it will be necessary only to compare them with healthy tissue expression profiles and find out about drug properties. There are already databases that offer such information, e.g., ChEMB and L1000 Viewer. The latter allows scientists to learn what gene expressions have an impact on certain medicines. This algorithm has helped make a prediction of the effectiveness of six candidate drugs for treating gastric cancer.

Insilico Medicine, the world-famous international company, made a success of this approach by announcing its preclinical studies of a candidate molecule for kidney fibrosis treatment [100 that showed the required pharmacological properties both in vivo and in vitro]. The entire process took 18 months. At the same time, research similar to this generally needs years. Before that, the company had also used omics data to find a new target for idiopathic lung fibrosis.

To sum it up, omics data can bring us closer to individualized medicine. Probably, three decades from now, doctors will analyze their patients’ omics data to search for the right drug, observe their reaction to treatment, and change the prescription or dosage if it is necessary.

Machine learning and computer vision

Studies on disorders of the central nervous system comprise the second-highest number of failed preclinical trials. Since 2011, R&D departments of large companies have constantly been canceling their research even on diseases like Alzheimer’s.

The problem is that CNS disorders progress depending on environmental aspects and hereditary and may vary in severity and symptoms. More than that, preclinical trials do not even try to recreate all the influencing characteristics.

For instance, the main risk factor for strokes is age. At the same time, most in vitro research is done by applying cells of “healthy male mice.” When testing the effectiveness of new medicines on this dubious sample set, researchers ignore bad habits or comorbidities. Consequently, we should not forget the general biological differences between people and mice. The models used for tests are too distant from reality.

Moreover, the Diagnostic and Statistical Manual of Mental Disorders proves that, unlike animal counterparts, people have a lot of various behavioral patterns. During preclinical trials, these patterns are underestimated and are approximately assessed in terms of basic animalistic reactions. How many times did the most stop running? For how long did it stay near the wall of the cage? What is the maximum speed at which it can run in circles?

AI technologies can assist in studies like those to determine some verisimilitude. For instance, some preclinical trials already apply behavioral phenotyping.

This method uses the automated analysis of videos that display moving animals. Special programs define behavioral patterns that are based on body positions, typical movements, and gestures.

MoSeq (Motion Sequencing) is one such algorithm. It is used to test neuro- and psychoactive drugs. Watching hundreds of 20-minute videos, the algorithm can identify the pharmacological class and dosage of a substance administered to animals. The behavioral reactions defined by MoSeq helped the researchers to determine previously unknown similarities and differences between them, as well as revealed adverse effects of administered drugs.

The number of software based on computer vision and machines will most probably increase over the next three decades and boost the efficiency of preclinical trials.

Moreover, methods of AI and ML can greatly improve the success rate of drug development if they are applied to select clinical trial volunteers. They can also provide “smart” quality control of clinical data and on-site performance results.

Held back by the law

Legislation is still a critical factor that has an impact on the speed and use of technologies. Today’s approaches to clinical trials must follow detailed protocols to ensure compliance with scientific procedures and prevent potentially dangerous drugs from being released.

Even the most well-developed countries have laws that prohibit drug development based only on computer modeling. Animal tests and the participation of human volunteers are obligatory for any clinical trials, and AI methods can be used as supporting means only.

However, it seems clear the legislation will change soon when more and more success stories of AI-centered trials occur. By the middle of the 21st century, more than just several drugs that had in silico tests playing an essential role in their development will be introduced into the market. Even now, the latest technologies make the development process quicker and cost-efficient, and in the future, they will also make it more efficient.

To summarize, researchers keep using new ways to solve modern challenges and confirm the efficiency and safety of new medicines. They include both in vitro (3D cell cultures and OOCs) and in silico (computer models) methods. Maybe we will be witnesses of the times when the development of a new medicine does not make any living creature suffer, and its introduction to the market takes only months rather than years.

Rustam Gilfanov is a venture partner of the LongeVC fund, a venture investment fund formed to support startups in the field of biotechnology and longevity at the initial stages of development.

Why Is Skincare Cavitation Necessary?

As we get older, the skin’s natural elasticity slowly decreases. Although it’s a universally known fact that collagen production decreases as we age, the loss of elasticity is something that few people are aware of. And because of that, many middle-aged women are suffering from loose skin that can sag or hang. Not only does loose skin make you look older, but it can also lead to a number of other problems, including bad posture, and even cause chronic pain in the back and neck area.

However, it should come as no surprise that these concerns are largely preventable, thanks to the wonders of skincare cavitation. It is the use of a special device that passes high-energy sound waves over the skin’s surface, which triggers the body to produce new collagen fibers and repair damaged ones. Call it a miracle treatment for aging skin, as it’s capable of making your skin look years younger in just a few short weeks!

While surgical dermabrasion and micro-needling are other methods for reducing wrinkles, both methods require invasive procedures, which can be very painful and expensive. And why go for surgical options when you can get the same results from a gentle, non-invasive procedure such as skincare cavitation? Not only is it much gentler on your skin than laser surgery, but it’s also much faster and affordable – not to mention less painful. Plus, since you don’t need to undergo any surgical procedures, you won’t have to worry about a lengthy recovery period either.

But the real question that rings in every woman’s mind is: is skincare cavitation safe? Well, the short answer is yes! Cosmetic skincare cavitation is a safe procedure with minimal to no side effects. It is perfect for all skin types, including those with sensitive skin.

One of the remarkable things that most people don’t realize is that the effectiveness of skincare cavitation is not limited to a particular age group. In fact, most people who have used skincare cavitation are in their 30’s, 40’s, and 50’s. With zero downtime, skincare cavitation is the perfect procedure for both men and women and can be done as often as every two weeks for the best results. Once you receive your skincare cavitation machine and start your first treatment, you will feel some mild vibrations on your skin. While there are multiple companies out there that offer this type of technology, we recommend using a high-quality brand such as those provided by myChway for the best results:

During your skincare cavitation treatments, you will feel a warm sensation on your skin and hear a buzzing sound from the machine. However, you can minimize this sensation by simply using the lowest setting on the device. The warmth produced by the machine is just an indication that the machinery is working and the bubbles are being formed. Once the procedure is completed, all you need to do is apply a moisturizing cream or lotion to restore hydration to the skin.


Wear your Patriotism through Official Patriot Gear®

America has always been a place of opportunity for all, but many were left with few options during the later months of 2020. Fueled by a desire to help struggling small businesses, Ian Wendt rallied together his social media following to raise funds to keep businesses, and the American dream, alive and well. 

As his reach grew, so did his mission. After raising tens of thousands of dollars for individuals all over the country, Ian recognized the beauty in the fact that not one of the people who donated ever asked who the money was going to; they were simply willing to help their fellow Americans, regardless of what they believed in or where they came from. Ian was struck with the realization that what he was experiencing was the true definition of the word patriot. His supporters continued to ask for ways to help, so he created the patriot tee as a way for people to show their pride, patriotism, and support for the United States and the people within it. 

What began with a single olive tee quickly grew into a worldwide brand and movement. “I felt called to something bigger and chose to leave my former career behind. Starting with the original Patriot tee, I began producing more and more products as the demand grew and gave people worldwide a voice and a way to stand up for what they believed in and lived every day. I never planned on starting a brand. I only wanted to raise awareness, spread truth, stand up for freedom and give everyone who wanted to do the same a way to,” shared Ian Wendt.  Patriot’s message of unity and being willing to stand for freedom resonated with individuals across the globe, who proudly show their love of their country by sporting the patriot logo. The beauty of the Patriot® name is that regardless of what country you occupy, if you love your country and the people in it, and you want them to be free and thrive, and you’re willing to defend those freedoms, that country, and those people, you are a patriot. 

Official Patriot Gear® is owned and operated by Ian and Madeline Wendt. Based out of Idaho, their flagship store opens later this year and continues to create American jobs as it expands. Each Patriot® Friday, the brand grows as individuals in over 48 countries proudly represent it while sharing their love of the country. 

Meet Cole Luis DaSilva-Business Mentor to 1400 Fitness Coaches

With the fitness industry expanding and evolving continuously, the need for personal trainers and fitness coaches has increased drastically. Today, people prefer a personal experience; an experience they can enjoy and feel connected with, rather than blatantly following others. But while we only get to see the work of fitness coaches, little do we know about those who are actually behind their success. Have you ever wondered who makes these fitness enthusiasts into successful coaches and who helps them connect with clients while growing and revolutionizing the fitness industry?  

These are business mentors, people with extraordinary entrepreneurial skills, the energy that never fades and, most importantly, passion for achieving what no one ever has. And there is no better example than Cole Luis DaSilva, a man who has not only helped hundreds of individuals transform their lives through fitness but now mentors over 1400 fitness coaches to grow their online businesses.  

Coming from the industry himself, Cole DaSilva understands how incredibly hard it can be to grow and reach your target audience. This is why he teaches personal trainers how to start and scale their online businesses so that they can escape the rat race once and for all.   

Today, Cole makes a seven-figure income and is living his dream life.  

However, it wasn’t always this easy. 

Growing up in Thunder Bay, Ontario, Cole’s only focus when he was younger was drinking and drugs after dealing with financial struggles and abuse when he was a child. He ended up trying to face life on his own, couch surfing at the age of 15 and eventually finding his roots around the age of 20 when he moved to Calgary, Alberta, to become an ironworker. 

Even though he thought that would be a fresh start, unfortunately, it didn’t end up that way. Not having a lot of friends, he’s included himself very quickly, focusing on only work in the bar, and after a year or so, he developed a Percocet addiction. Spiraling out of control, he found himself thousands of dollars in debt, alone, and struggling with alcohol and Percocets.  

It wasn’t until he found fitness that his life changed completely. “If it weren’t for fitness, I wouldn’t be here today.” 

“Fitness saved me. Not only did it give me an outlet to escape my current situation, but it let me down the path of self-improvement, personal training, so I could help others, and now business coaching rum impact in thousands,” explained Cole Luis DaSilva. 

Though Cole does not have a fancy business degree, it did not stop him from excelling as a businessman. 

After being stuck in an ironworking job for three years, Cole got two group training certifications and became a personal trainer. He worked as a personal trainer at an up-north location at Fort Mac for only three months before deciding it was time for him to start his own venture. 

He then got certified as a sports nutritionist, a certified personal trainer, and a bodybuilding specialist through ISSA while beginning his online business. 

And the rest is history. Cole then went on to help hundreds of individuals transform. Their bodies are fitness online beside his business partner and best friend Brian Mark today.

And since then, he has not only started his own clothing brand Amarok Aesthetics, but he has also bought a gym alongside his business partner and best friend and started an extremely successful business coaching company PT Domination, where he helps personal trainers and online fitness coaches grow their online businesses.  

He has a social media following of 1 million over multiple platforms and has helped around 2500 online trainers start their online businesses, with eight of them earning over $100,000 online organically & over 270 earning over $10,000 a month organically.

Being an online entrepreneur is lonely; this was perhaps one of the primary motivations behind starting PT Domination. “We wanted to build other online entrepreneurs so they could live the same way we are,” he revealed. Moreover, because he had worked as a trainer himself, he understood the struggles that went into it. “Not to mention, I understand what it’s like to be a personal trainer at a gym. I only did it for three months, and not only did it barely pay, I also got treated horribly,” he added.  

From struggling with his addictions to becoming a passionate fitness enthusiast who has worked with big names like Phil Heath: 7-time Mr. Olympia Champion, Bedros Keuilian & more, Cole Luis DaSilva has come a long way. And there is no stopping him.  

However, he doesn’t take all the credit for his success. “My partner Brian Mark has truly inspired me. When I met him, I hired him to be my fitness coach because I needed to get away from drinking and drugs. I wanted to change my life,” Cole informed. “While I was training under him for my first fitness competition, I watched him work as an online entrepreneur. Seeing that he was able to generate an astounding income as well as impact countless people from home was something that sparked my mind and made me want to pursue the same thing.” 

Every once in a while, we come across people who, with their determination and enthusiasm, change the way things work, and Cole Luis DaSilva is surely one of them. 

This relentless young man lives without regrets, knows what he wants, and goes for it. After all, he believes that when you show up every single day regardless of how you feel and give your 100%, you are bound to get results!

A Botanist’s Dream Come True: Botanic Choice and Its Efforts to Promote Natural Wellness Since 1910

The most impactful of companies across all sectors started as a dream translated into reality. Then, it was up to its founders for that reality to include long-term success and a legacy for future generations to remember. Joseph Meyer, the mind behind Indiana Botanic Gardens and its brands Botanic Choice and Botanic Spa, accomplished all that and more in the years following the creation of his company in 1910. Today, his brainchild continues to thrive and stay afloat amid a sea of wellness-focused ventures in the saturated business world, a feat that only some founders can bag under their belt. 

Born in Wisconsin, Joseph Meyer has always held a deep-seated interest in plants and nature. His father, a photographer, often let him tag along during assignments in forests and fields. And while the passion-fueled go-getter had to change tracks and take up a more practical career in printing because of financial hiccups, the Botanic Choice founder would eventually find his way back, growing and harvesting plants in a vacant lot at the back of his Indiana home and building what would flourish into an industry powerhouse in a small cottage. 

From a cottage in Indiana to the forefront of the wellness scene, Joseph Meyer’s Indiana Botanic Gardens has come to occupy a significant space in the century since its launch. Currently, the Indiana Century Award recipient is led by Tim Cleland, and Tammy Cleland has remained a family-owned provider of high-quality natural formulas, beauty care, nutritional supplements, and vitamins. 

Widely considered America’s choice for high-quality, research-based vitamins, supplements, and beauty care products, Botanic Choice brings to the table over 100 years of experience and an in-depth understanding of what it takes to foster health. At its heart still stands the overarching mission to make effective natural health solutions available to all. 

Right now, Botanic Choice boasts three lines of ingestible: essentials, exclusive formulas, and premium formulas, all of which were created with quality as the topmost priority. “We have always been relentlessly focused on safety and quality to ensure you are getting the very best that nature has to offer,” said the purpose-driven leaders of Indiana Botanic Gardens, Inc. “That’s why we have developed rigorous quality control processes and procedures that meet or exceed standards in everything we do.”

Over the years, Botanic Choice has undeniably reached great heights thanks to its selection of effective and cost-effective nutritional supplements, vitamins, minerals, and proprietary formulas. Its rise can also be credited to its diverse and dedicated staff members, many of whom have been with the family for years. But, more than anything else, its emergence at the top and awe-inspiring longevity can be attributed to its most treasured asset – its loyal customer base. 

“Many of our current customers include the grandsons and granddaughters of past customers who passed down their tradition of good health to family members,” shared the team spearheading the efforts of Botanic Choice. 

Needless to say, Botanic Choice has created a legacy and cemented a tradition that dates back 100 years ago. Its success is expected to run for more generations to come as it stays dedicated to helping others lead healthier, happier lives the natural way.