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In the Eye of the Corona Storm: A Drug That Works

By Shlomo Maital

   

Yaky Yanay

    My good friend Dr. G. N. Rao, founder of the L V Prasad Eye Institute in Hyderabad, India, drew my attention to this:   A coronavirus drug that works.

     According to Maayan Jaffe-Hoffman, writing in the Jerusalem Post:

   “Israeli-based Pluristem has treated its first American patient suffering from COVID-19 complications under the country’s compassionate use program.

 The news comes days after a report by the company showed that six critically ill coronavirus patients in Israel who are considered high-risk for mortality were treated with Pluristem’s placenta-based cell-therapy product and survived, according to preliminary data provided by the Haifa-based company.

Let me provide some background.

Researchers report: “When it comes to COVID-19, recent research has suggested about 20% of people get the severe form of the disease. Many in this group become critically ill because of their advanced age or underlying health conditions. But those who were previously healthy and are in their 30s, 40s, 50s are very likely experiencing a cytokine storm.”

A small but significant fraction of COVID-19 patients, mainly younger ones, die not from the ravages of the virus on their lungs, but because their body over-reacts, as their immune system kicks in violently and creates this “cytokine storm”. It turns out that an overly strong immune reaction is just as bad, or worse, than a weak reaction.

How does Pluristem’s drug work? Here is how CEO Yaky Yanay explains it:

“Patients who are in severe condition and dying are actually dying from a severe respiratory condition. What is actually happening is there is a very high level of inflammation and at a certain point the immune system of the patient will attack [the patient], mostly in the lungs.   Until now, Pluristem’s technology has been largely used to treat people suffering from poor blood flow to the legs, but the company’s scientists were able to quickly repurpose the cells to treat coronavirus patients.   “We take cells from the placenta after full-term delivery and we have developed technology to expand the cells to very large numbers, in an environment that mimics the human body,” Yanay said. “The technology allows us to treat more than 20,000 people from a single placenta.”

       His team “programs” the cells, which then have a wide range of proteins they can secrete. The cells don’t just deliver the proteins but also “adjust the level of secretion based on signals they receive from the body.”

       The US FDA allows using the drug on compassionate grounds for very seriously ill patients. But for widespread use, full-scale three-phase clinical trials are necessary, and are already well underway.

COVID-19: Why Do More Men Die Than Women?

By Shlomo Maital

 

Women live longer than men. It’s true. Here are the facts, from the World Health Organization:

     In 2019, more than 141 million children will be born: 73 million boys and 68 million girls.  

     Based on recent mortality risks the boys will live, on average, 69.8 years and the girls 74.2 years – a difference of 4.4 years.

       Life expectancy at age 60 years is also greater for women than men: 21.9 versus 19.0 years.

       Women have a longer life expectancy than men at all ages.

     Many years ago, when I studied demography at Princeton (at Ansley Coale’s famed Office of Population Research), this fact was true even then – and I read a study of monks and friars, in a monastery, whose life expectancy reflected the same advantage for women – so, it is not environmental factors that cause it.

     In fact, we’re not really sure why women live longer. There are many theories.

   And now, comes COVID-19. Writing in the daily Haaretz, Asaf Ronal observes that the mortality rate from COVID-19 for men is 2.8%, while the mortality rate for women is 1.7%. That is a massive difference. This is adjusted for age, and other factors.

     Why?

   There are theories. Behavioral: Men are ‘heroes’ and seek medical care less than women. Physiological: Female hormones protect them. Immunological: Female immune systems work better. Biological: the ‘receptors’ viruses like to invade on human cells reside in part in Chromosome X, women have two copies of it, thus they are more susceptible, so their immune systems are more alert and wary to attack invaders.

       These are all theories. None have really been fully tested.

       And finally, my own observation: As we observe spatial separation here in Israel, and as I watch both men and women experts explain things and advise us on TV – again, as always, I am struck by how much better women are at delivering information, credibly, authentically, than men, given the same level of expertise and training.

     If only the men would leave it to the women – and just shut up. US President, are you listening? And Israeli PM?   Men — take care of yourselves.  Let the women run things.  They do it better.

 

 How to Cure Cancer: Zelig Eshhar’s Breakthrough

By Shlomo Maital

Eshhar

Prof. Zelig Eshhar

 

   Media reports last week brought exciting news about a new breakthrough in the fight to cure cancer.

       In an article in the journal Science Translational Medicine, a team at the University of Pennsylvania’s Abramson Cancer Center and the Perelman School of Medicine reported that 27 out of 29 patients with an advanced blood cancer saw their cancers go into remission or disappear altogether when they received genetically modified T-cells that were equipped with synthetic molecules called chimeric antigen receptors, or CARs. Those T-cells were able to target and destroy the tumor cells – specifically the ones that were responsible for the acute lymphoblastic leukemia the patients were suffering from. According to officials at the Fred Hutchinson Cancer Research Center, where the research was carried out, patients in the trial – some of whom were told in 2013 they had barely a few months to live – not only survived, but now, after the therapy, “have no sign of the disease.”

One of the pioneers of this approach is Prof. Zelig Eshhar, of Israel’s Weizmann Institute. According to press accounts:   “Eshhar has been conducting T-cell research for over a decade, and in 2014 was recognized by leading industry publication Human Gene Therapy for his work, along with Dr. Carl June of the University of Pennsylvania for their work in the field. In an article called “From the Mouse Cage to Human Therapy: A Personal Perspective of the Emergence of T-bodies/Chimeric Antigen Receptor T Cells,” published for the occasion, Eshhar laid out the mechanics of CAR T-cell immunotherapy – showing how his work on mice progressed to the point where the American team was able to pick up the cudgel and conduct a study on humans. With that. Eshhar cautioned Wednesday, the breakthrough did not in any way represent a “cure for cancer” – at least not yet. “Obviously much more work is needed,” he said. “One issue with this kind of therapy is that you have to develop specific T-cells for each kind of cancer. But studies like those are a great impetus to move forward with research. I believe the day will come when we will see many more cancers treated in this manner.”

     T-cells are the white blood cells produced by our immune systems that fight invading germs and microbes (and cancer cells). But they are generally too weak to fight off cancer cells, which have several clever defense mechanisms. However, by removing T-cells, and genetically modifying them, they can be strengthened – a bit like taking a Chevrolet Impala and souping it up with a Corvette 400 hp. engine. Eshhar has cured mice of cancer using this method, and the U. of Pennsylvania team extended his method to humans, with success.

     Will such T-cell therapy defeat all cancer, not just a form of leukemia and lymphoma? Let us hope!    

Ebola — Fact vs Fiction

By Shlomo Maital

ebola

As a would-be journalist, I’ve followed closely how the media report on the Ebola virus epidemic in Africa.   America’s NPR (National Public Radio) is excellent – but even NPR has spread hysteria and has reported very badly on the issue.   There is something about this deadly little virus that kills half the people it afflicts, that frightens people. And the media play into these fears, by amplifying them. Shame on them.

The Economist rides to the rescue. As always it brings us the truth, with the facts well explained.   In the Oct. 18 issue, here is what The Economist explains:

  • The number of infections (in West Africa – mainly Sierra Leone, Guinea and Liberia) is doubling every 2-4 weeks.   Meanwhile, though, Senegal and Nigeria have been declared ebola free. So it is possible to stamp it out.
  • If something doubles every, say, 3 weeks,   then in 10 doublings (30 weeks, or about half a year), it is 1,024 times greater.   So if 10,000 people have Ebola virus today in West Africa, 10 million will have it in half a year. This is why it is so urgent to come to the rescue of these three countries.
  • If the West does wake up and send help, the goal is simple: Get the infectious rate down, in West Africa,  from 1.5 to 2.2 persons per infected person (i.e. every person who has Ebola infects 1.5 to 2.2 other persons, today), to less than 1.   If this ratio, known as Ro, is less than one, then the power of compounding works to our favor.   Soon, Ebola disappears.     You can only get the Ro number down by having more hospitals, more trained health workers, faster medical care, etc.   Get people infected to quarantine quickly.  This is done instantly in the West,  but West Africa does not have the means. 
  • This is not a Western problem YET.   The West has a moral obligation to help West Africa, whose economies have been devastated.   But it WILL be a Western problem, if a half year goes by and the Ro remains at around 2. Then the Ebola will simply not be capable of being stamped out.
  • Why is Ebola so fatal and so dangerous? Because it is fiendishly clever, even though of course it does not have a brain. Ebola virus invades a cell, and makes it produce more viruses instead of the cell’s own DNA. Ebola has sugars on the outside coating of the virus, making it tough for the body’s immune system to attack it (antibodies stick to the glycoprotein instead of to the virus). The immune cells that the virus attacks race to the spleen, liver and lymph nodes and thus carry the infection there. Soon, the body over-reacts, and blood vessel walls become leaky, organs fail and the body goes into shock. President Obama has sent 3,000 U.S. soldiers to help Liberia. Much more is needed. Europe, of course, is sound asleep. And a lot of the money promised to   West Africa remains just that – a promise.   Unless the rich countries wake up, they will find themselves dealing with a problem that is one hundred times harder to solve.

 

  • All this – from a tiny virus!   How did it get so smart? It evolved – nature’s accidents created viruses that survive to procreate.

Blog entries written by Prof. Shlomo Maital

Shlomo Maital

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