Tag: Coronavirus

Senolytics showcase link between life extension and therapeutics

A significant part of ongoing anti-aging research has conventional applications in the treatment of gerontological conditions while also opening up potential avenues for life extension. Two entrepreneurs – Lewis Gruber of Siwa Therapeutics and Marc Ramis Castelltort of Senolytic Therapeutics and Rejuversen AG – discuss how their cutting-edge research serves two purposes – to improve health at old age, and to move one step closer to the dream of vastly expanded human longevity.

Over the past three to four decades, scientists have refined their understanding of cellular aging processes and their effects, in terms both of specific pathologies and of the overall biological aging of the body. These insights have opened up ways to treatments that may one day help us achieve vastly extended health- and lifespans simultaneously. Indeed, among the potentially life-extending interventions that companies are actively researching today, there are many approaches that could not only help us live longer, but could also pave the way for new cures for specific illnesses and conditions that are currently untreatable. Given the close overlap between clinical therapeutics for diseases and life extension research, some even argue that “aging” should be considered a condition in its own right.

A glance at companies’ portfolios confirms this nexus between life extension and disease treatment. There is no firewall between longevity research and conventional medical R&D. A prime example is the field of cellular senescence, in which researchers use senolytic compounds to try and kill off “zombie” cells that have reached Hayflick’s Limit and stopped dividing due to shortening of telomeres. These senescent cells emit cytokines that cause inflammation and immune cell activation in the surrounding tissue and can even induce senescence in healthy cells. Cytokines are especially important in regulating the immune response, and research on immunosenescence ties in with more general efforts to understand the functioning and eventual dysfunction of the immune system, which have gained urgency in connection with the COVID-19 pandemic.

COVID-19 research: full speed ahead

“Although the pandemic has caused a slowdown in many areas, any solutions that are potentially effective in stopping the coronavirus will of course be fast-tracked,” said Lewis Gruber, CEO and co-founder of Siwa Therapeutics, in a recent interview with Supertrends. This biopharmaceutical company, based in Chicago, USA, has developed a humanized monoclonal antibody, SIWA 318H, which it hopes can directly target cells affected by viruses, including COVID-19. The antibody seeks out cells that have an abnormally high level of glycolysis and oxidative stress. Among these are cancerous, senescent, and virally infected cells.

“By removing those cells, we eliminate deleterious [damaging] secretions and stimulate regenerative processes,” Gruber explains. While the company remains focused on aggressive cancers, the devastation wreaked by COVID-19 has prompted Siwa Therapeutics to test its antibody as a potential treatment for infectious diseases and related cytokine storms and as a potential building block for a vaccine against the novel coronavirus.

Expanding lifespans – and health-spans

Another company that concentrates on the removal of senescent cells is Senolytic Therapeutics, a Barcelona-based biotech firm seeking to develop novel medicines and drugs for life extension and health improvement while also offering consulting services to other firms in the biotech sphere. The company’s co-founder, Marc Ramis Castelltort, noted in an interview with Supertrends that the main focus for now is on conventional life extension: “We are developing senolytic-based drugs that can treat diseases including fibrosis and certain forms of cancer. To the extent that such therapies can help people live longer, we are also expanding their lifespans, but our main goal for now is the treatment of pathologies that are associated with the biology of aging.” With support from the EU’s Horizon 2020 research and innovation program, the company hopes to come up with new medicines to combat fibrotic diseases and other age-related disorders.

Nevertheless, the insights that Castelltort and his team have gained into cellular aging and the role of senescent cells as a cause of frailty in old people have prompted him to found a second company, Rejuversen AG, which hopes to find cures for therapy-induced senescence in the field of oncology. “We aim to be able to present our first clinical trial by 2023,” he says.


“Although we are still at the discovery stage, we are confident that we will soon be able to treat aging-associated diseases and thus extend not only our lifespans, but also our ‘health-spans” (Marc Ramis Castelltort)

The best approach to do this, according to Castelltort, is to treat age-related diseases first and then life extension as two sides of the same coin.


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The new challenge in fighting old sepsis

While we have been battling with sepsis for centuries, now COVID19 added new challenges to this battle. Can Aquaporin-based therapy be our newest weapon against this malicious viral sepsis?


“Patients typically develop a high fever, their Interleukin 6 (IL-6) is high. If we can get them to pass the two-week mark, they will survive.” Dr. Masab Moumneh, MD, ICU physician


Sepsis – an elusive syndrome

Sepsis has been defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. First described by Hippocrates, it is one of the oldest topics in the history of medicine. Even with advances in care, it remains a global public health emergency affecting millions of people worldwide and one of the main causes of death across the world. Sepsis is also one of the costliest conditions in hospitals. Accounting for more than US$20 billion (5.2 percent) of total US hospital costs, it was the most expensive condition treated in US hospitals in 2011.

Despite the worldwide importance of sepsis, public awareness remains low. In a survey conducted in 2009 in Italy, Spain, the UK, France, and the US, 88 percent of interviewees had never heard of the term “sepsis” – and from those who did recognize the term, 58 percent were not aware that sepsis is a leading cause of death. Similar results were found in another survey in 2014 in South Korea.

The reason for the elusiveness of sepsis probably lies in the fact that sepsis is not a specific illness, but rather a syndrome encompassing a still-uncertain pathobiology. It is recognized today that a complex and multi-factorial host response is responsible for the development of sepsis. Infection triggers both pro-inflammatory and anti-inflammatory processes that ultimately contribute to both the clearance of infection and the tissue damage that lead to organ failure.

Viral sepsis and cytokine storm

Previously, bacterial infections were usually regarded as a leading cause of sepsis. The COVID-19 crisis has brought viral sepsis into the spotlight. In a study of 191 COVID-19 patients treated in December 2019 and January 2020 in Wuhan (China), sepsis was found to be the most frequently observed complication. Sepsis was diagnosed in 59 percent of all patients included in the study. Furthermore, 100 percent of the non-survivor patients were diagnosed with sepsis. Was it viral sepsis that was killing the COVID-19 patients?

To understand the immune reaction in viral infections, we have to understand the phenomena triggered by cytokine and cytokine storms. Cytokines are a group of proteins. Through a process called cell signaling (communication between cells), cytokines control inflammation in our body. When we get an infection, our immune system releases more cytokines. Unfortunately, sometimes the body goes into overdrive and releases more cytokines than it should. As the body loses control of cytokine production, a “cytokine storm” is created. Cytokine storms might explain why some people have severe reactions to the coronavirus while others only experience mild symptoms.

In another study from Wuhan, viral sepsis and cytokine storms were more directly linked to critically ill COVID-19 patients. This study found that pro-inflammatory cytokines and chemokines were significantly elevated in COVID-19 patients. It further suggested that the cytokine storm might play an important role in the immunopathology of COVID-19.

“I have never seen anything as bad as this. COVID-19 patients were killed by cytokine storms,” said Dr. Masab Moumneh, who has been an ICU physician in Abu Dhabi for the past ten years. Of the 700 hospital beds in the public hospital where Dr. Moumneh works, 110 are ICU beds. From April to June 2020, at the height of the COVID-19 crisis in the United Arab Emirates, Dr. Moumneh and his colleagues saw a 38 percent mortality rate in their ICU COVID-19 patients – a very respectable survival rate.

A search for dedicated immune suppressor

Working on the assumption that it was the cytokine storms that were causing the deaths of COVID-19 patients, Dr. Moumneh and his colleagues tried to use drugs that could reduce the overreaction of the immune system. In their ICU wards, corticosteroids – the standard anti-inflammatory medicine – were administered once COVID-19 patients were admitted. Although they were not included in the official guideline of sepsis management[1], corticosteroids were the only immunomodulator that was recommended for regulating overreacting immune systems in the guidance on “Care of Critically Ill Patients With COVID-19”, published by US National Institutes of Health [2].

Discovered in the 1940s, corticosteroids are one of the most widely used and effective treatments for inflammatory and autoimmune diseases. However, they do cause serious adverse effects, especially if used over a longer term or in high doses. Doctors have been looking at using newer immunosuppressants to develop more effective treatment options. Attempts by Dr. Moumneh and his colleagues to find other effective and safe immunosuppressants were unsuccessful. “One of the newer immunosuppressants caused bowel perforation, and the patient died,” Dr. Moumneh said regretfully. The fact is that at the moment, there is no dedicated medicine that explicitly targets immune over-reaction in sepsis or viral sepsis.

Can an Aquaporin-based drug fill the gap?

Aquaporins (AQPs) are channel proteins that form pores in cell membranes. As such, they are involved in a wide range of physiological functions. In general, aquaporins play a role in maintaining a constant water homeostasis and homeostasis of many physiological processes. There is solid evidence that AQPs facilitate both phagocytic functions of immune cells and migration of immune cells [3] [4] [5]. Furthermore, research has demonstrated that AQPs contribute to regulating fluid trafficking and inflammation process in lung infection [6]. This could be particularly helpful in seeking remedies for COVID-19 patients. Clinical data indicate that mortality attributable to COVID-19 infection is mainly due to the development of viral pneumonia-induced acute respiratory distress syndrome (ARDS) [7].


Cytokine storms and viral sepsis are serious complications of virus infections such as COVID-19, SARS, MERS, and the flu. They have caused hundreds of thousands of deaths around the world. Supertrends would like to help by supporting a community that focuses on fighting sepsis, especially viral sepsis. If you are interested in joining our community, please reach out to us to share your ideas, research, or inspirations at https://supertrends.com/call-for-experts/.
© 2020 Supertrends

Reference

[1] Rhodes, A, LE Evans et al. 2017. “Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.” Intensive Care Med 43:304–377.

[2] NIH. 2020. COVID-19 Treatment Guidelines. 27 August. https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/.

[3] Zhu, N., X. Feng, C. He, H. Gao, L. Yang, and Q Ma. 2011. “Defective macrophage function in aquaporin-3 deficiency.” FASEB J. 25, 4233–4239.

[4] Loitto, V. M., T. Forslund, T. Sundqvist, K. E. Magnusson, and M. Gustafsson. 2002. “Neutrophil leukocyte motility requires directed water influx.” J. Leukoc. Biol. 71, 212–222.

[5] Tyteca, D., T. Nishino, H. Debaix, P. Van Der Smissen, F. N’Kuli, and D. Hoffmann. 2015. “Regulation of macrophage motility by the water channel aquaporin-1: crucial role of M0/M2 phenotype switch.” PLoS ONE 10: e0117398.

[6] Towne, J. E., K. S. Harrod, C. M. Krane, and A. G. Menon. 2000. “Decreased expression of aquaporin (AQP1) and AQP5 in mouse lung following acute viral infection.” Am. J. Respir. Cell Mol. Biol. 22, 34–44.

[7] WHO. 2020. Coronavirus disease (COVID-19) Pandemic. https://www.who.int/emergencies/diseases/novel-coronavirus-2019.

A doctor’s view on managing the COVID-19 crisis

COVID-19 is at the top of agendas worldwide, and many articles have been published in the past weeks on the best way to move forward. In an interview with Supertrends, Jørgen Thorball, a medical doctor with a solid track record of developing medical innovations, makes some practical suggestions from the view of an experienced medical doctor and a visionary life science entrepreneur.


“With testing and treatment, I believe it is very likely we will be able to quickly manage the COVID-19 crisis.” Dr. Jørgen Thorball, MD


At a time when one of the hottest debates is about when, and not if, a vaccine will be the silver bullet in our war against COVID-19, Thorball notes that no vaccine has ever been successfully developed for a coronavirus so far. Although new technologies and significantly more funding are now available, success in developing a safe and effective vaccine has so far remained elusive.

Priorities: Vaccination or treatment?

Description automatically generated“If everything goes well, we may see a vaccine developed by the end of this year. By the middle of next year, it may be possible to vaccine the general population in the US, Europe, and other parts of the world,” Thorball believes. But he cautions that we should be realistic in our expectations: “Let’s not forget that this will be an innovative technology, which means we cannot assume that everything will go well. My sense is that finding a vaccine is a gamble, while finding the optimal treatment and testing is simply a matter of going through the normal working process of clinical trials. I am worried that we are not putting enough efforts into optimizing the treatments we already have within our grasp for patients and ensuring better preventive measures for high-risk populations.”

Scaling up the testing system to control the crisis

If we cannot bet on a vaccine, what should we bet on? Thorball thinks the key is testing and treatment. Unlike the development of a new vaccine, the process of testing and using existing medicine for treatment does not involve innovation, but optimization.

Advances in gene sequencing technology have enabled scientists to trace and monitor the COVID-19 pandemic faster than any previous outbreak. A significant decline in the cost of genetic synthesis also helps us to scale up the diagnostic tests.

In Thorball’s view, there are three levels of testing that can help with managing the COVID-19 crisis:

  1. Inflammation biomarker testing to screen who is at higher risk. We already know that the inflammation level is directly linked to mortality and the severity of symptoms. Biomarkers can be used to monitor the inflammation level. This can be used to help determine who in the population that will need higher level of protection and who will need to remain in hospital and be monitored more carefully.
  2. Diagnostic testing to screen who is infected and isolate those who are infected. “It may sound expensive to test everybody very often. But people tend to forget that the diagnostic test is a volume game. These tests can be at ridiculously low prices if we really want,” Thorball points out.
  3. Antibody test to identify who is presumably immune. People who already have antibodies can be assigned to higher-risk jobs, such as homecare etc.

If we combine these 3 testing methods in a smart program that adapts to the mix of people, their individual situation and the local infection pressure in a given week, then most people will be able to go back to a normal life. More and smarter testing will also help doctors improve current treatments as Thorball believes it is more promising to find a better combination of existing medical treatments that together can reduce COVID-19 mortality significantly. “With a much more efficient testing program and some improvement in the treatment and prevention that we already have or are in clinical trials, we are likely to push down the mortality to around the seasonal flu, which we should remember is the goal we should be aiming for, and we will rather quickly be able to manage the COVID-19 crisis,” Thorball believes.

Opening the human virome’s black box

A person in the laboratory, covid-19

One of the positive outcomes of the COVID-19 crisis might be a much-improved understanding of how viruses behave in and affect the human body. Thorball is hopeful that this may be the beginning of a new megatrend in research based on a more detailed knowledge of the human virome, i.e., the entirety of viruses living in and on the human body: “The human virome will be the new fantastic black box that’s going to open up.”

So far, the behavior and functions of viruses in the human body are not yet well understood. Scientists are eager to learn more about how they infect human cells as well as other microbes, such as bacteria, and why some viruses cause disease, while others do not trigger any symptoms at all. Thorball hopes that a closer study of the virome could help explain how certain viruses are integrated into the human genome.


Medical breakthroughs can come as rapid and unexpected as the COVID-19 crisis. We at Supertrends are trying to build a comprehensive timeline of future innovations and technological breakthroughs, to have a better grasp of what lies ahead of us. Sounds interesting to you? Learn more about our Supertrends Pro app and request a trial to see what Supertrends experts and our community have predicted for the future.

© 2020 Supertrends

Lessons learned in China may help others in combating coronavirus

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first recorded in mid-December 2019 in Wuhan, China. However, it was not until 20 January 2020 that the Chinese authorities officially confirmed incidents of human-to-human transmission and admitted concerns about a major outbreak. Over the following days, both the death toll and the number of infections shot up as one Chinese city after another was locked down.

The current coronavirus situation

As of mid-March, it appears that China has finally managed to bring the outbreak under control after huge losses of human life and economic costs. However, these experiences are now being repeated outside of China as the coronavirus disease 2019 (COVID-19) is quickly spreading globally. On 11 March 2020, the coronavirus outbreak was designated a pandemic by the World Health Organization (WHO).

Are we about to see the same scenes repeat themselves all over again in other parts of the world, or will we be able to manage the pandemic better by taking into account the lessons learned in China? To understand what China has learned about the virus, I talked by phone to Supertrends expert Dr. Wenji Dong from Beijing, who has conducted research on gene therapy using viral vectors and has experienced at first hand the battle against the coronavirus in China.

Supertrends: How do you assess the outlook for the coronavirus outbreak?

Wenji Dong: Given the measures taken by authorities around the world and with the arrival of spring and summer, my prediction is that we will see a turning point in the coronavirus outbreak at the end of April or early May this year.

However, I think there is a high possibility that the virus will make a comeback when winter returns. Unlike SARS and MERS, this new coronavirus is highly contagious and difficult to identify, with relatively high pathogenicity. It is like a reinforced super virus – coronavirus version 2.0. It will probably take two to three years for this virus to go away completely.

What would be our best weapon against the coronavirus? Will it be medicine, antibodies from plasma-derived therapy, or a vaccine?

China has been testing more than 100 drugs. It takes so long time to complete clinical trials that we don’t even have enough patients now to complete the trials. I think Remdesivir is a promising medicine; however, it may not be possible to complete clinical trials within this year.

Theoretically, the antibodies developed by recovered patients might be used to strengthen the immune system of new patients. But it is almost impossible to scale up and industrialize this method. It is more suitable as personalized treatment. The solution to this is could be by cloning antibody genes from B cells of recovered patients, which may take longer time.

With our efforts to develop a vaccine, time is again the issue. The number of patients will be much lower when the weather turns warmer. This will cause difficulty in developing a vaccine.

Will we face this kind of virus outbreak more frequently in the future? What can we do if this happens?

I think so. SARS, MERS, and COVID-19 all belong to the family of betacoronaviruses. There are many kinds of coronavirus. I think it is likely that a similar virus outbreak will happen again.

The best control strategy against infectious disease outbreaks is to respond quickly and contain the infection source. China has done quite well this time in stopping the source of infection.

It may not be realistic to develop a vaccination against this particular virus, but it may be possible to develop vaccinations and medication against the virus family. Another thing to consider when developing a vaccination for coronavirus is antibody-dependence enhancement. This is a phenomenon in which preexisting poorly neutralizing antibodies leads to over-reaction of the immune system and is a potential risk for a coronavirus vaccination.

Have new developments in gene sequencing and genomics benefited the diagnosis and treatment of COVID-19?

Definitely. Developments in the field of gene sequencing and genomics have helped us to identify the genome sequence and develop the test kit very quickly. That is something that has never happened before. Gene sequencing technology can be used for the diagnosis of any infectious disease.

While the number of cases in Europe, Iran, and the US is growing rapidly, the control measures in China have been relaxed, and the focus is now more on containing imported cases. As WHO Director-General Tedros Adhanom Ghebreyesus noted, the steps China has taken to contain the outbreak at its source appear to have bought the world time. It is up to the world to use that time efficiently.

Supertrends expert Wenji Dong graduated with a Ph.D. in biochemistry and molecular biology from Beijing Union Medical College. He has worked with some of the top professors in molecular biology in China and as a team leader for national research projects. He is the founder of a gene therapy start-up company GenMedicn.


Gene sequencing and genomics will have an enormous impact on the future of healthcare. Read Supertrends editor Jiqing’ Hansens blog “Genomics Spells the End of ‘One Size Fits All’ Medicine” to learn more about it.

© 2020 Supertrends

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