▎WuXi AppTec Content Team Report
The countdown to the 2022 Nobel Prize begins. As the highest honor in the scientific community, the Nobel Prize has gone through more than a century. In the past 100 years, scientists have made a series of breakthrough discoveries and research progress, making pioneering contributions to the development of science and the progress of human society. Among them, there are some discoveries that are closely related to human health and life. They not only deepen human understanding of basic biology, but also open up new ideas and directions for us to overcome diseases. This article takes stock of 10 categories of innovative treatments based on Nobel Prize-winning discoveries and how they are all helping humans overcome disease.
1
Hepatitis C Virus Discovery
2020 Nobel Prize in Physiology or Medicine
Representative drugs: antiviral drugs for hepatitis C
Blood-borne hepatitis is a global health problem, yet most cases of blood-borne hepatitis remain unexplained. The 2020 Nobel Prize in Physiology or Medicine was awarded to three scientists for the discovery of the hepatitis C virus (HCV). Their contribution is a milestone in the history of human fight against viral diseases. The discovery of the hepatitis C virus made possible blood tests, which eliminated post-transfusion hepatitis in many parts of the world. In addition, thanks to the discovery of the hepatitis C virus, the antiviral drug for hepatitis C has made rapid research progress, making the hepatitis C disease cured for the first time in history.
2
Oxygen Sensing Pathway
2019 Nobel Prize in Physiology or Medicine
Representative drugs: roxadustat, belzutifan, daprodustat
Oxygen is essential for the survival of humans and most animals, and elucidating biological oxygen sensing pathways is of great value. The 2019 Nobel Prize in Physiology or Medicine is awarded to scientists who have made significant contributions to the research of oxygen sensing pathways. This major discovery is of great significance to the research and development of innovative drugs. For example, by regulating the hypoxia-inducible factor-1 (HIF-1) pathway and promoting the production of red blood cells, it is expected to treat anemia. Interfering with the degradation of HIF-1 protein can promote angiogenesis and treat poor circulation. In addition, since tumor growth is inseparable from new blood vessels, if HIF-1α or related proteins can be degraded, it is expected to fight against malignant tumors.
At present, a number of innovative therapies based on the “oxygen sensing pathway” have been approved for marketing, including: Oxygen-inducible factor prolyl hydroxylase inhibitor
Roxadustat
Approved in China and EU for the treatment of patients with anemia due to chronic kidney disease; hypoxia-inducible factor inhibitor
belzutifan
FDA-approved for von Hippel-Lindau (VHL) disease-related cancer; hypoxia-inducible factor prolyl hydroxylase inhibitor
daprodustat
Approved in Japan for the treatment of patients with renal anemia, and filed for marketing in the US and EU.
3
Negative immunomodulation in cancer treatment
2018 Nobel Prize in Physiology or Medicine
Representative therapy: anti-CTLA-4 antibody, anti-PD-1 antibody
In the body’s immune system, there are T cells that act as “policemen”, and when they find abnormal cells on patrol, they eliminate them. However, the more “police” the better, the overactive T cells can damage normal cells and cause autoimmune diseases. Therefore, under normal circumstances, the human body will let T cells stop in time through a mechanism similar to the “brake” system. CTLA-4 and PD-1 are members of this “brake” system. However, the researchers found that cunning cancer cells have also evolved a superior ability to “kick the brakes” in order to escape immune cell attack.
So scientists have developed immunotherapies that inhibit CTLA-4, PD-1, and kill cancer cells by disarming their “brake-on” system. The emergence of immunotherapy represented by anti-CTLA-4 antibody and anti-PD-1 antibody is a milestone in the history of human overcoming cancer, and such innovative therapies have benefited different types of cancer patients. In 2018, the Nobel Prize in Physiology or Medicine was awarded to the discoverers of CTLA-4 and PD-1 for their pioneering contributions to the field of cancer immunotherapy.
4
Phage Display Technology
2018 Nobel Prize in Chemistry
Representative drug: adalimumab
Bacteriophages are viruses that infect bacteria. In 1985, scientists pioneered a method called “phage display,” which won the 2018 Nobel Prize in Chemistry. ShouldThe principle of the technology is: First, scientists introduce foreign genes into the phage coat protein gene sequence; then, these foreign genes are co-expressed with the phage coat protein and displayed on the phage surface. On demand, researchers can screen for proteins with certain properties on the surface of these phages. Subsequently, the genes encoding these proteins were reintroduced into the phage. This repeated “evolution” can get the protein that researchers need.
And directed evolution of antibodies through phage display holds the promise of developing better antibody drugs. Hummira (adalimumab) was the first drug developed based on this technology, and has been on the market since 2003. It has helped many patients with immune diseases around the world. In addition, “phage display” produced a variety of antibodies that can neutralize toxins, fight autoimmune diseases, and cure metastatic cancers.
5
New treatments for malaria, roundworm and other parasitic infections
2015 Nobel Prize in Physiology or Medicine
Representative drugs: artemisinin, abamectin
Malaria is one of the diseases caused by parasites that have plagued humans for thousands of years. The traditional treatment for malaria is the use of chloroquine or quinine, but the success rate of this method is declining, and malaria infection rates are on the rise. Chinese scientist Tu Youyou extracted artemisinin with a brand new chemical structure from Artemisia annua. Artemisinin can quickly kill malaria parasites at an early stage and significantly reduce the mortality rate of malaria patients.
Onchocerciasis and lymphatic filariasis are two other types of diseases caused by parasites. Irish scientist William C. Campbell and Japanese scientist Satoshi ōmura have discovered a new treatment against roundworm infection-AverbacterVine . Abamectin derivatives can fundamentally reduce the occurrence of onchocerciasis and lymphatic filariasis, and also have a good effect on the control of the number of other parasitic diseases.
Both of these discoveries were awarded the 2015 Nobel Prize in Physiology or Medicine. The selection committee for the Nobel Prize in Physiology or Medicine noted that the discovery of artemisinin and abamectin has fundamentally changed the treatment of parasitic diseases.
6
Regulatory mechanisms of vesicular transport
2013 Nobel Prize in Physiology or Medicine
Representative therapy: exosome therapy
In the human body, basic life processes such as energy conversion between cells, information recognition and transmission, and material transport are carried out all the time, and the accurate execution of these processes is inseparable from the intracellular “Logistics system” – vesicles. Vsicles are like “postmen”, they package the molecules to be transported (proteins, nucleic acids, etc.) and deliver them to the right place at the right time. Scientists who discovered the “regulatory mechanism of vesicle trafficking” in cells were awarded the Nobel Prize in Physiology or Medicine in 2013.
The discovery brings new ideas for researchers to develop drugs. Exosomes are a type of vesicles. As natural intercellular information carriers, they have become one of the ideal targets for scientists to develop drug delivery vehicles. Small molecule drugs, gene therapy drugs (miRNA, etc.), protein drugs, etc. can all be loaded onto exosomes. Exosome-based drugs are expected to address some of the limitations of protein, antibody and nucleic acid therapy. In addition, the brain has become a difficult point for various drug development due to the existence of the blood-brain barrier, and exosomes may be a way to bypass this barrier. Currently, many companies are developing exosome carriers to deliver multiple drugs, which are intended to be used to treat cancer, central nervous system, rare diseases and other diseases.
7
Re-“programming” mature cells
2012 Nobel Prize in Physiology or Medicine
Representative Therapy: Stem Cell Therapy
Stem cells are a type of cells with infinite or immortal self-renewal capacity. Stem cells in the embryonic stage can develop into various cell types in mature living organisms such as nerve cells and muscle cells. This process has always been considered to be one-way and irreversible. However, studies have found that mature cells can actually “rejuvenate”. After reprogramming, adult somatic cells can be reinduced back into an early stem cell state for the formation of various cell types. Stem cells generated by this technique are called induced pluripotent stem cells (iPSCs). The discovery was awarded the 2012 Nobel Prize in Physiology or Medicine.
This revolutionary discovery opens up new horizons in the treatment of disease. At present, a new generation of stem cell therapy based on gene and cell modification is emerging, and these therapies are expected to improve the effectiveness and specificity of stem cell therapy, for inflammation, autoimmune diseases, heart failure, stroke, Parkinson’s disease, diabetes, New options for the treatment of genetic diseases, etc..
8
HPV infection causes cervical cancer
2008 Nobel Prize in Physiology or Medicine
Representative Therapy: Cervical Cancer Vaccine
Cervical cancer, also known as cervical cancer, is a common malignant tumor in women.one of cancer. Studies have found that HPV (human papillomavirus) infection is the main cause of cervical cancer. Based on this major discovery, scientists have successfully developed a vaccine to prevent cervical cancer, and several HPV vaccines have been approved worldwide. The arrival of the HPV vaccine is epoch-making because it is the first vaccine in human history to prevent cancer. Cervical cancer has thus become the only cancer with a clear etiology and early detection and prevention. In 2008, scientists who discovered that HPV causes cervical cancer have been awarded the Nobel Prize in Physiology or Medicine.
9
RNA interference phenomena
2006 Nobel Prize in Physiology or Medicine
Representative therapy: RNAi therapy
RNA interference (RNAi) is a method of gene silencing through double-stranded RNA. As we all know, many diseases are caused by genetic mutations, and the breakthrough technology of RNAi has given scientists the hope of treating diseases through “gene silencing”. In 2006, scientists who discovered the phenomenon of RNA interference were awarded the Nobel Prize in Physiology or Medicine.
After 12 years of being awarded the Nobel Prize, humanity has finally ushered in the first RNAi therapy. In 2018, the siRNA therapy Onpattro (patisiran) developed by Alnylam was approved in the United States for adult patients with peripheral nerve disease caused by hereditary transthyretin amyloidosis.
First Approved
Marketed RNAi therapy. At present, RNAi therapy is still a popular direction for new drug research and development. The treatment areas to be developed include rare diseases, cardiovascular diseases, non-alcoholic steatohepatitis, and cancer. As of August this year, 5 RNAi therapies have been approved for marketing worldwide.
10
The ubiquitin-proteasome system
Nobel Prize in Chemistry 2004
Representative Therapies: Targeted Protein Degradation Drugs
The ubiquitin-proteasome system was discovered by scientists in the late 1970s and early 1980s.It is the main pathway of intracellular protein degradation and is involved in more than 80% of Protein degradation. In the ubiquitin-proteasome system, cells add some ubiquitin molecules to proteins that need to be degraded, which is like putting a “recyclable” mark on “junk”. These ubiquitin-tagged proteins are then delivered to the proteasome in the cell. The latter is like a garbage disposal center, breaking down proteins into short peptides and amino acids for cells to synthesize other proteins. This discovery was awarded the 2004 Nobel Prize in Chemistry.
In fact, degrading proteins is very important for disease treatment. The underlying cause of many serious diseases is protein dysfunction. However, conventional small-molecule drugs and antibody drugs can only inhibit about 20% of proteins, and the remaining about 80% are labeled as “undruggable”. Targeted protein degradation drugs based on the ubiquitin-proteasome system are expected to overcome this problem. Currently, scientists are developing targeted protein degradation drugs for the treatment of cancer, autoimmune diseases and other diseases. According to incomplete statistics, as of March 2022, more than 20 drugs in this field have entered the clinical trial stage, and more than 140 drugs are in preclinical research.
Summary
In addition to the above, there are many innovative technologies and therapies based on Nobel Prize discoveries, such as CDK 4/6 inhibitors, insulin, vitamins K, prontosil, monoclonal antibodies, in vitro fertilization technology, etc. Due to space limitations, this article will not introduce them one by one. Here, I would like to pay tribute to all the scientists who have made contributions to conquering human diseases and improving human health. I hope they can make more breakthrough discoveries in the future and bring new tools for mankind to conquer diseases!
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