What is the medicine Trump gave himself urgently?

 What is the medicine Trump gave himself urgently?

According to Trump’s personal doctor, Sean P. Conley, Trump did not use the hydroxychloroquine that he had previously recommended, but began to use a product that has not yet been approved by the U.S. Food and Drug Administration (FDA). The approved new drug is a mixed antibody from the US "Regeneron" (Regeneron).

The treatment idea of ​​this medicine is very old. It was thought up more than 100 years ago. This is the plasma therapy that was born in the late 19th century. The Prussian bacteriologist Emil Adolf von Behring, who was the first to try this therapy, won the Nobel Prize in Physiology or Medicine in 1901, and was the first recipient after the award was established.

Simply put, plasma therapy is to infect mammals with a certain pathogen, and then collect plasma after it recovers, and use it to treat the same type of human infectious diseases. Behring used this method to treat diphtheria successfully and saved countless children's lives.

It now appears that the principle of plasma therapy is very simple. The blood of recovered mammals must contain targeted antibodies that can "neutralize" the invading enemy. So this therapy is essentially similar to a vaccine, except that the vaccine must cooperate with the recipient’s own immune system to produce protective antibodies against the pathogen. Plasma therapy bypasses this step and directly provides the patient with protective antibodies. The effect is similar.

Scientists at the end of the 19th century did not know exactly what the antigen-antibody reaction was going on. They just intuitively believed that the cured person's body must contain some kind of chemical substance that can kill the pathogen. After Beilin won the award, doctors tried plasma therapy to treat smallpox, measles, scarlet fever, tetanus and polio, all with good results. But when preventive vaccines for these infectious diseases were invented, plasma therapy was abandoned.

However, the doctors did not completely forget this method. When the Ebola epidemic just broke out, doctors did not know how to deal with it, so they tried serum therapy to treat critically ill patients, but they could not find a suitable animal reservoir at the time, and could only mobilize Ebola patients who were lucky enough to recover. Of plasma.

When the new crown epidemic first started, doctors were also helpless and tried plasma therapy. In fact, Trump held a press conference at the White House on August 23 this year to announce that plasma therapy was officially approved. At that time, 79,059 new crown patients in the United States had used this therapy.

These patients received the healer's plasma through a temporarily organized mutual aid group composed of Arturo Casadevall (Arturo Casadevall) of Johns Hopkins University and Mikel of the Mayo Clinic. Three doctors, Michael Joyner and Liise-anne Pirofski of the Albert Einstein School of Medicine, organized it in their spare time. These three doctors are over 60 years old, and there is no pressure to be promoted, and they are no longer just thinking about making money. You know, this project will not make money, nor will it earn them any scientific reputation, but will let them take risks. But these three are all experienced doctors, knowing that plasma therapy is likely to be effective, and they are willing to take certain risks to save lives. Facts have proved that plasma therapy does have a certain effect. A small controlled trial involving 525 severely ill patients proved that the therapy has a 57% lower mortality rate than the control group.

However, the scale of this controlled trial is still too small and the design is not rigorous enough to prove that plasma therapy is indeed effective. If the U.S. government really intends to approve this therapy, it must conduct a formal Phase III clinical trial, and determine the plasma specifications, dosage, usage, side effects and many other indicators through the test, which can be considered as meeting the requirements. One very important reason why Trump rushed to announce the approval of plasma therapy before the completion of the formal clinical trial was to win votes. He did not expect that he might use it so soon.

Antibody therapy

For obvious reasons, even if plasma therapy passes the Phase III clinical trial, it cannot become a panacea for ending the current epidemic. After all, this method requires the cured patient to actively donate his own plasma, and every patient cured is likely to require several recovery. The patient’s plasma is sufficient, the source of raw materials cannot be guaranteed, and it is difficult to benefit more patients. To solve this problem, the only way to find a way to produce plasma-like drugs in the factory.

Advances in immunology have made scientists realize that what really works in plasma therapy is antibodies, and antibodies themselves are a kind of protein. As long as they can figure out a way to produce this protein, there is no need to draw blood from mammals or recovered patients. Up.

This idea is simple to say, but it is extremely difficult to operate, because antibodies are a very complex protein, and it is extremely difficult to produce antibody proteins in vitro. In the early years, scientists used cell fusion technology to fuse cancer cells with B cells that produce antibodies, creating a fusion cell line that has both the immortal proliferation ability of cancer cells and the antibody production ability of B cells. But this method is very difficult, it takes a long time to test to succeed, and there is no time to deal with new infectious diseases.

After the emergence of molecular biology technology, scientists can introduce antibody-encoding genes into yeast cells or mammalian cells, and then culture these cells in a fermenter to produce specific antibody proteins. The cost of antibody protein produced by this method has been reduced a lot, and it has certain practicability. In theory, it can be used to produce a large number of monoclonal antibodies against specific pathogens.

Take the new crown as an example. Scientists can first extract the plasma of recovered patients, extract antibodies against the new crown virus from it, determine the amino acid sequence of the antibody, and then infer the DNA sequence encoding the antibody protein, and then introduce this piece of DNA into something In the cells of a mammal, a large number of new crown monoclonal antibodies can be produced through cell culture.

When the SARS outbreak broke out, some scientists tried this method, but it was abandoned halfway because the SARS epidemic ended too early. However, the research that year was not in vain. Dr. Victor Padilla-Sanchez of the Catholic University of America used computer analysis to test the two antibodies against the SARS virus discovered that year. 80R and m396 have been fine-tuned to make them better respond to the new coronavirus. In doing so, there is no need to start anew, as long as a small change to the DNA sequence of the SARS antibody can be used for COVID-19.

Eli Lilly of the United States united with several other biotechnology companies and officially opened the first clinical trial of a new crown monoclonal antibody on May 29. The treatment target was a severely ill patient who was admitted to the hospital. Eli Lilly’s vice president of immunology, Ajay Nirula, believes that monoclonal antibody therapy can help patients with new coronary disease alleviate pain and reduce mortality before the vaccine is released. This is because monoclonal antibodies are highly targeted. , Should be much better than those antiviral drugs such as Remdesivir or Dexamethasone, which are rushed into battle by temporarily changing the indications.

Almost at the same time, the American "Regeneron Pharmaceutical Company" also started its own clinical trials. They extracted two new coronavirus antibodies from a COVID-19 recovery patient, and transferred the genes encoding these two antibodies into mice by the aforementioned method, and the mice produced the two antibodies (named respectively) It is an antibody cocktail of REGN10987 and REGN10933). On September 22 this year, the company announced the first batch of test results. For those patients who have mild symptoms and do not need to go to the hospital, the antibody cocktail can significantly reduce the viral load, especially for those with poor immunity. The effect is most significant for patients who produce sufficiently strong antibodies.

Advantages and disadvantages of antibody therapy

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), is optimistic about the future of antibody therapy. "If you want to make a bet, I suggest you put your money on monoclonal antibodies." Fauci once told reporters: "Before the vaccine comes out, monoclonal antibodies are likely to be the most effective solution."

Antibody therapy can also be called "Passive Immunity" therapy, because the principle of this therapy is similar to that of vaccines. The difference is that vaccines actively attack pathogens by activating the human immune system, while monoclonal antibodies assist immunity. System, passively declare war on pathogens. Because it is passive, the efficacy of antibody therapy can only last for about 3 weeks, after which the antibody will gradually be degraded and lose its protective function. But also because it is passive, antibody therapy does not require patients to have a healthy immune system, and the benefits are very obvious for the elderly, the weak, and the disabled.

Antibody therapy has another advantage over vaccines, that is, monoclonal antibodies are therapeutic drugs for patients, not preventive vaccines for healthy people. Therefore, clinical trial subjects of monoclonal antibodies are easy to find and require safety. If it is lower, the approval speed will be faster, and it will be less likely to be resisted by anti-vaccineists, making it easier to promote.

However, monoclonal antibodies have an insurmountable disadvantage, that is, they are too expensive. Although gene recombination technology has been greatly improved in recent years, the production of protein in vitro is still a very complicated task and the cost remains high. For example, the average price of monoclonal antibody therapy in the United States in 2018 was US$96,000 per person per year. If it is used on the new crown, the price will certainly not be so high, but it is not affordable for ordinary people. Of course, if Trump needs it, he can definitely afford it.

Because antibody therapy has too many shortcomings, the US government's new crown "Operation Warp Speed" (Operation Warp Speed) invested most of the funds for vaccines, and only invested $750 million in antibody therapy. The funded Eli Lilly company promised to produce 100,000 doses of monoclonal antibodies by the end of 2020, but the United States alone needs at least 40 million doses of monoclonal antibodies, which is obviously not enough.

Although antibody therapy is difficult to promote on a large scale in the short term, it represents a new direction for immunological research. I hope that this new crown epidemic will make everyone realize that infectious diseases are not far away from us. Large-scale infectious diseases like the new crown will certainly appear many times in the future. The government and enterprises should change their thinking, invest sufficient research funds in advance, develop a large number of faster and better treatment methods, and prepare in advance.2020/10