On January 27, 2021, Deep Longevity, a fully-owned subsidiary of Regent Pacific (HKEX: 0575), specializing in the development and the application of next-generation artificial intelligence (AI) for aging and longevity research, announced the January 14, 2021 online publication of an open-access article in Nature Aging titled “Artificial Intelligence in Longevity Medicine” (www.nature.com/articles/s43587-020-00020-4). In the article, the authors describe a new field of study converging AI, basic research, and medicine referred to as Longevity Medicine. Another definition for Longevity Medicine is the preventative and restorative medicine enabled by the deep-aging clocks and artificial intelligence. The article was authored by Alex Zhavoronkov, PhD, the Founder and Chief Longevity Officer of Deep Longevity, a computer scientist with a doctoral degree in biophysics; Evelyne Yehudit Bischof, MD, MPH, a practicing medical doctor trained in the top European and the US medical schools actively engaged in aging research and gero-oncology at the University Hospital Basel in Switzerland, and at Shanghai University of Medicine and Health Sciences; and Kai-Fu Lee, PhD, one of the most prolific scientists and entrepreneurs in artificial intelligence, and Chairman and CEO of Sinovation Ventures (www.sinovationventures.com/). The traditional approach to medicine is to treat diseases. However, scientists estimate (Cutler and Mattson, 2006) that complete elimination of cancer would result in only a 2.3-year increase in life expectancy in the US at birth and 1.3-year gain at age 65. Complete elimination of influenza and pneumonia would yield gains of 0.5 years and 0.2 years in life expectancy in general.
An international research team, co-led by the Technische Universität Kaiserslautern (TUK), has identified a vulnerability in most cancer cells that could help lead to drugs that target tumors regardless of cancer type. Cancer cells with an abnormally high number of chromosomes appear to rely on a particular protein (KIF18A) for cell division and largely die when that protein is blocked, researchers in Germany, Israel, Italy, and the US report in an online publication on January 27,2021 in Nature (www.nature.com/articles/s41586-020-03114-6). The article is titled “Aneuploidy Renders Cancer Cells Vulnerable to Mitotic Checkpoint Inhibition.” Because more than 90 percent of tumors, regardless of tissue type, contain extra chromosomes, this protein could present an effective target for treating a wide range of cancers. “We think we have found a possible vulnerability of cancer cells with abnormal chromosome numbers,” says Zuzana Storchová, PhD, a Professor of Molecular Genetics at the Technische Universität Kaiserslautern (TUK) in Germany, and a co-senior author of the Nature article. Normal, healthy human cells have 46 chromosomes, but malignant tumors often consist of highly abnormal cancer cells that can have deviant chromosome numbers, usually ranging between 60 to 90 chromosomes. They are called aneuploid cancer cells. For a long time, researchers thought aneuploidy was a side-effect of cells turning cancerous, but in the last 15 years, more suspect this might be one of the driving forces of cancer. Finding a common feature associated with this aberrant number of chromosomes could be critical for targeting cancer, regardless of where it develops in the body. Dr. Storchová and collaborators conducted extensive experiments with nearly 1,000 cell lines from human cancer patients and model cancer cells cultured in the lab.
More effective antiviral treatments could be on the way after research from The University of Texas at Austin (UT-Austin) sheds new light on the COVID-19 antiviral drug remdesivir, the only treatment of its kind currently approved in the U.S. for the coronavirus SARS-CoV-2. The study was published online on January 28, 2021 in Molecular Cell. The article is titled “Remdesivir Is a Delayed Translocation Inhibitor of SARS CoV-2 Replication.” Remdesivir targets a part of the coronavirus that allows it to make copies of itself and spread through the body. For the first time, scientists identified a critical mechanism that the drug uses and unearthed information that drug companies can use to develop new and improved antivirals to take advantage of the same trick. According to co-author Kenneth Johnson, PhD, Professor of Biochemistry at UT-Austin, the finding could also lead to more potent drugs, meaning a patient could take less of a dose, see fewer side effects, and experience faster relief. “Right now, it’s a five-day regimen of taking quite a bit of remdesivir,” said Dr. Johnson. “That’s inconvenient and comes with side effects. What if you could take just one pill and that was all you needed to do? That would make a huge difference in terms of the here and now.”Study co-author David Taylor, PhD, Assistant Professor of Molecular Biosciences at UT-Austin, likens the trick the team identified to a paper jam in the virus’s photocopier. Remdesivir shuts down this photocopier–called an RNA polymerase–by preventing copying of the virus’s genetic code and its ability to churn out duplicates and spread through the body. The team detected where the drug manages to gum up the gears, grinding the machine to a halt. “We were able to identify the point where that paper jam happens,” said Dr. Taylor. “We know now exactly what’s creating this block.
Many genetic mutations have been found to be associated with a person’s risk of developing Parkinson’s disease. Yet, for most of these variants, the mechanism through which they act remains unclear. Now a new study in Nature (www.nature.com/articles/s41586-021-03185-z) published online on January 27, 2021, and led by a team from the University of Pennsylvania (Penn), has revealed how two different variations—one that increases disease risk and leads to more severe disease in people who develop Parkinson’s and another that reduces risk—manifest in the body. The work, led by Dejian Ren (photo)(https://www.bio.upenn.edu/people/dejian-ren), PhD, Professor of Biology in the School of Arts & Sciences’ Department of Biology at Penn, showed that the variation that raises disease risk, which about 17% of people possess, causes a reduction in function of an ion channel in cellular organelles called lysosomes, also known as cells’ waste removal and recycling centers. Meanwhile, a different variation that reduces Parkinson’s disease risk by about 20% and is present in 7% of the general population enhances the activity of the same ion channel. The Nature article is titled “A growth-factor-activated lysosomal K+ channel regulates Parkinson’s pathology.” “We started with the basic biology, wanting to understand how these lysosomal channels are controlled,” says Dr. Ren. “But here we found this clear connection with Parkinson’s disease. To see that you can have a variation in an ion channel gene that can change the odds of developing Parkinson’s both ways—increasing and decreasing it—is highly novel.” The fact that the channel seems to play a crucial role in Parkinson’s also makes it an appealing potential target for a drug that could slow the disease’s progression, the researchers note.
Building on the promise of emerging therapies to deploy the body’s “natural killer” immune cells to fight cancer, researchers at the University of Michigan (U-M) Rogel Cancer Center and U-M College of Engineering have gone one step further. They’ve developed what is believed to be the first systematic way to capture natural killer cells and get them to release cancer-killing exosomes. These nano-scale exosomes are thousands of times smaller than natural killer (NK) cells and thus better able to penetrate cancer cells’ defenses. A proof-of-concept study in blood samples from five patients with non-small cell lung cancer demonstrated that the approach was able to capture natural killer cells on a microfluidic chip and use them to release NK exosomes. The multidisciplinary team, which included U-M engineers and oncologists, further demonstrated that the exosomes could effectively kill circulating tumor cells in cell cultures, according to findings published online on January 28, 2021 in Advanced Science. The open-access article is titled “On‐Chip Biogenesis of Circulating NK Cell‐Derived Exosomes in Non‐Small Cell Lung Cancer Exhibits Antitumoral Activity.” “Exosomes are small sacs, of proteins and/or other molecules, that are naturally released by almost every type of cell in the body,” says Yoon-Tae Kang, PhD, a Research Fellow in Chemical Engineering at U-M and co-lead author of the study. “In this case, we wanted to expand our understanding of NK exosomes and try to harness their cancer-killing potential.” Compared to NK cells, NK exosomes are more stable and easier to modify for therapeutic purposes, Dr. Kang says. The system also has potential to help diagnose and monitor cancer, the study notes. Harnessing the power of NK cells has long presented a tantalizing possibility for researchers.
Researchers from McGill University (Montreal, Canada) have discovered, for the first time, one of the possible mechanisms that contributes to the ability of lysergic acid diethylamide (LSD) to increase social interaction. The findings, which could help unlock potential therapeutic applications in treating certain psychiatric diseases, including anxiety and alcohol use disorders, we published online on January 25, 2021 in PNAS. The open-access article is titled “Lysergic Acid Diethylamide (LSD) Promotes Social Behavior Through mTORC1 in the Excitatory Neurotransmission.” Psychedelic drugs, including LSD, were popular in the 1970s (see image of early LSD advocate Dr. Timothy Leary) and have been gaining popularity over the past decade, with reports of young professionals claiming to regularly take small non-hallucinogenic micro-doses of LSD to boost their productivity and creativity and to increase their empathy. The mechanism of action of LSD on the brain, however, has remained a mystery. To conduct their study, the researchers administered a low dose of LSD to mice over a period of seven days, resulting in an observable increase in the sociability of the mice. “This increased sociability occurs because the LSD activates the serotonin 5-HT2A receptors and the AMPA receptors, which is a glutamate receptor–the main brain excitatory neurotransmitters–in the prefrontal cortex, and also activates a cellular protein called mTORC 1,” explains Danilo De Gregorio, PharmD, PhD, who is a postdoctoral fellow in the Neurobiological Psychiatry Unit at McGill, and the study’s first author. “These three factors, taken together, promote social interaction in mice, which is the equivalent of empathy and social behavior in humans.” [Editor’s Note: 5-HT2A is the abbreviation for 5-hydroxytryptamine receptor 2A.
Hepatocellular carcinoma (HCC) is the most common primary liver tumor with an increasing global incidence. In 2018, HCC was the sixth most frequently diagnosed cancer and the fourth-leading cause of cancer-related death worldwide. Sorafenib is the first FDA-approved targeted therapy for advanced HCC. A previous study showed that sorafenib prolonged the median overall survival (OS) by 2.3−3 months in advanced HCC patients that did not qualify for liver transplantation or resection. However, sorafenib resistance in HCC is usually observed within 6 months of treatment, thereby making the follow-up therapy rather formidable. Recently, a research team led by Professor Xiujun Cai (photo) (person.zju.edu.cn/en/0094417?utm_source=miragenews&utm_medium=miragenews&utm_campaign=news), PhD, from Sir Run-Run Shaw Hospital affiliated with the Zhejiang University School of Medicine has made breakthroughs in sorafenib resistance. Dr. Cai is the President of Sir Run Run Shaw Hospital of Zhejiang University and the Director of both the Institute of Minimally Invasive Surgery of Zhejiang University and the Key Lab of Surgery of Zhejiang Province. The new findings were published online on December 26, 2020 in Signal Transduction and Targeted Therapy. The open-access article is titled “CircRNA-SORE Mediates Sorafenib Resistance in Hepatocellular Carcinoma by Stabilizing YBX1” (www.nature.com/articles/s41392-020-00375-5.pdf?utm_source=miragenews&utm_medium=miragenews&utm_campaign=news). The experiment results elucidate the crucial role of circRNA-SORE (a circular RNA upregulated in sorafenib-resistant HCC cells) in sorafenib resistance and its functioning mechanism.
On January 26, 2021, Split Biosciences, a company providing researchers scalable and flexible single-cell sequencing solutions, announced $7M in Series A funding. The funding round was led by Bioeconomy Capital, an early-stage VC firm specializing in companies developing life science tools, with participation from new and existing angel investors. Split Bio also announced a rebrand of the company to Parse Biosciences (www.parsebiosciences.com/). The new funding will be used to continue scaling the commercial roll-out of Parse Bioscience’s Whole Transcriptome Kit, which enables researchers to profile up to 100,000 cells in parallel across up to 48 samples. In addition to increased scalability, Parse Biosciences’s technology also provides researchers with higher data quality. Parse enables researchers to increase gene detection in individual cells, while dramatically reducing confounding artifacts that are common in single-cell sequencing experiments. The new brand comes as Parse Biosciences matures beyond the initial academic research upon which the company was founded and in the wake of significant advancements in its technology. “We have spent the last three years developing a product that more scientists could actually use,” said Charlie Roco, PhD, Co-Founder and CTO of Parse Biosciences. “Our kits are now operating at a higher level than anything else we’ve seen on the market and our company has evolved beyond our original SPLiT-seq method. We wanted our brand to reflect that.” Researchers in both the pharmaceutical industry and academia have increasingly leveraged single-cell technologies to drive discovery.
The highlight of Monday’s opening day of the Precision Medicine World Conference Virtual Meeting (PMWC 2021) “21st Century Precision Medicine in the Age of COVID-19” (Jan 25-27) (www.pmwcintl.com/covid/) was an hour-long Q&A session in which the extraordinary scientist Leroy Hood, MD, PhD, interviewed Anthony Fauci (photo, see additional photos at end), MD, Director of the National Institute of Allergy & Infectious Diseases (NIAID) & US Leading Coronavirus Task Force Expert, covering a wide range of key COVID-19 topics. Dr. Hood also presented Dr. Fauci with the PMWC Luminary Award, which “recognizes individuals who have made significant contributions to accelerate personalized medicine within the clinical setting.” In presenting the Award, Dr. Hood added that, in addition to all his earlier achievements, the Award recognized Dr. Fauci’s “utterly stellar service in the last year.” Dr. Hood (www.pmwcintl.com/speaker/lee-hood_providence-health_2021covi) is world-renowned for his visionary work in spearheading the development of a suite of five automated instruments that have revolutionized biomedical, biochemical, genetic, and biologic research, as well as pharmaceutical development–the automated protein synthesizer, the automated protein sequencer, the automated DNA synthesizer, the automated DNA sequencer, and the ink-jet oligonucleotide synthesizer. Dr. Hood is currently Senior Vice President and Chief Strategy Officer for the Institute for Systems Biology (ISB) and Senior Vice President and Chief Science Office for Providence St. Joseph Health.
The U.S. prevalence of the autoimmune disease systemic lupus erythematosus (lupus) is 72.8 cases per 100,000 individuals, according to an analysis of population-based registries. The analysis, which was published online on January 20, 2021 in Arthritis & Rheumatology, found that the rate is 9 times higher for females than males (128.7 vs. 14.6 per 100,000), and it’s highest among American Indians/Alaska Natives and Black females. The open-access article is titled “Prevalence of Systemic Lupus Erythematosus in the United States: Estimates from a Meta‐Analysis of the Centers for Disease Control and Prevention National Lupus Registries.” The study’s investigators estimate that in 2018, a total of 204,295 persons in the United States had lupus. “This meta-analysis is a culmination of almost two decades of work from a network of five Centers of Disease Control and Prevention (CDC)-funded population-based registries and provides prevalence estimates for systemic lupus erythematosus among the major racial/ethnic demographics in the United States,” said lead author Peter M. Izmirly (photo), MD, of the New York University (NYU) School of Medicine. “These detailed estimates on how many Americans are affected by lupus may have implications for the various stakeholders who study and treat the disease.”[News release] [Arthritis & Rheumatology article]