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June 25th, 2020

Genetic Malfunction of Brain Astrocytes Triggers Migraine in Familial Hemiplegic Migraine Type 2 (FHM2), New Study Suggests

Migraine is one of the most disabling disorders, affecting one in seven people and causing a tremendous social and economic burden. Several findings suggest that migraine is a disease affecting a large part of the central nervous system and characterized by a global dysfunction in sensory information processing and integration, which also occurs between migraine episodes (interictal period). For example, patients with migraine exhibit increased cortical responses to sensory stimuli during the interictal period. At present, the cellular mechanisms responsible for these alterations are largely unknown. A team of neuroscientists led by Mirko Santello, PhD, at the Institute of Pharmacology and Toxicology of the University of Zurich (Switzerland), in collaboration with the University of Padua (Italy), has identified a new mechanism implicated in a special form of migraine caused by genetic mutation. The researchers report that familial hemiplegic migraine type 2 (FHM2) causes a malfunction of astrocytes in the cingulate cortex, a brain region that is involved in the feeling of pain. Astrocytes, specific star-shaped brain cells, are essential contributors to neuronal function and have a strong impact on brain circuits and behavior. These results were published online on June 3, 2020 in Science Advances. The open-access article is titled “Astrocyte Dysfunction Increases Cortical Dendritic Excitability and Promotes Cranial Pain In Familial Migraine.” "Despite their abundance, astrocytes have been relatively overlooked by neuroscientists," says Dr. Santello, the senior author of the study. Yet these cells are extremely important to clear transmitters released by neurons. In their study the researchers were able to show that in familial migraine the astrocytes cannot remove excessive transmitters released by neurons.

June 25th

Bacteriophages Might Be Used to Help Reduce COVID-19 Deaths, Review Suggests

Bacteriophages (phages) are viruses that specifically attack and destroy bacteria. According to an expert at the University of Birmingham (UK) and the Cancer Registry of Norway, bacterophage could be harnessed to combat bacterial infections in patients whose immune systems have been weakened by the SARS-CoV-2 virus that causes the COVID-19 disease. These viruses are harmless to humans and can be used to target and eliminate specific bacteria. They are of interest to scientists as a potential alternative to antibiotic treatments. In a new systematic review, published in the journal PHAGE: Therapy, Applications, and Research, two strategies are proposed, where bacteriophages could be used to treat bacterial infections in some patients with COVID-19. In the first approach, bacteriophages would be used to target secondary bacterial infections in patients' respiratory systems. These secondary infections are a possible cause of the high mortality rate, particularly among elderly patients. The aim is to use the bacteriophages to reduce the number of bacteria and limit their spread, giving the patients' immune systems more time to produce antibodies against SARS-CoV-2. The open-access review article was published online on June 23, 2020, and is titled “Bacteriophages Could Be a Potential Game Changer in the Trajectory of Coronavirus Disease (COVID-19).” Marcin Wojewodzic, PhD, a Marie Skodowska-Curie Research Fellow in the School of Biosciences at the University of Birmingham and now a researcher at the Cancer Registry of Norway, is the author of the study. He says: "By introducing bacteriophages, it may be possible to buy precious time for the patients' immune systems and it also offers a different, or complementary strategy to the standard antibiotic therapies." Professor Martha R.J.

Cowbirds Change Sex Ratio of Eggs Based on When Eggs Are Laid in Breeding Season; More Female Eggs Laid Early; More Male Eggs Laid Late; Large Sample Size May Have Allowed Scientists to Detect Seasonal Sex Bias for First Time in Brood-Parasite Birds

[This article was written by Ananya Sen, a graduate student in Microbiology at the University of Illinois at Urbana-Champaign. Ms. Sen is also a science writer and her articles can be found at http://ananyasen.web.illinois.edu/. This article was originally published as a Research News article by the University of Illinois News Bureau (https://news.illinois.edu/view/6367). Permission to reprint this article in BioQuick News has also been granted by Ms. Sen and approved by University of Illinois New Bureau Editor Diana Yates.] Brown-headed cowbirds show a bias in the sex ratio of their offspring, depending on the time of the breeding season, researchers report in a new study. More female than male offspring hatch early in the breeding season in May, and more male hatchlings emerge in July. Cowbirds are so-called “brood parasites.” They lay their eggs in the nests of other birds and let those birds raise the cowbird young. Prothonotary warblers (see photo and name explanation below) are a common host of cowbirds. “Warblers can’t tell the difference between their own offspring and cowbirds,” said Wendy Schelsky, PhD, (https://www.inhs.illinois.edu/directory/show/schelsky), a Principal Scientist at the Illinois Natural History Survey (INHS) and co-author of the study, which was published online on June 2, 2020 in the Journal of Avian Biology (https://onlinelibrary.wiley.com/doi/10.1111/jav.02560). The study is titled “A Seasonal Shift in Offspring Sex Ratio of the Brood Parasitic Brown‐Headed Cowbird (Molothrus ater).” “They do a really good job of raising cowbirds, even though cowbird chicks are larger and need more food.” Dr. Schelsky uses molecular tools and ecological experiments to study life-history traits related to predation and parasitism.

Personalized mRNA-Based Cancer Vaccine Targeting Patient’s Tumor Neoantigens, Combined with Immune Checkpoint Inhibitor Atezolizumab, Shows Clinical Activity in Patients with Advanced Solid Tumors; Phase 1b Results Presented at AACR Virtual Annual Meeting

On June 23, 2020, the American Association for Cancer Research (AACR) announced that treatment with the personalized cancer vaccine RO7198457 (https://www.cancer.gov/publications/dictionaries/cancer-drug/def/persona...), in combination with the PD-L1 immune checkpoint inhibitor atezolizumab (Tecentriq), was well-tolerated and showed clinical benefit in patients with advanced solid malignancies, according to results from a phase 1b clinical trial (https://clinicaltrials.gov/ct2/show/NCT03289962 ) presented at the AACR 2020 Virtual Annual Meeting II (https://www.aacr.org/meeting/aacr-annual-meeting-2020/aacr-virtual-annua...), held June 22-24. “Many cancers are able to successfully avoid the immune system, and we are only starting to understand the myriad ways in which cancers can do this,” said Juanita Lopez (photo), PhD, MB BChir (https://www.royalmarsden.nhs.uk/our-consultants-units-and-wards/consulta...), a physician/scientist who is a Consultant Medical Oncologist at the Phase I Drug Development Unit at the Royal Marsden National Health Services (NHS) Foundation Trust (UK) and the Institute of Cancer Research, specializing in early phase translational drug development and the treatment of patients with brain tumors. Dr. London presented the trial results on Tuesday morning, June 23, during the AACR meeting. The presentation (CT301) was titled “A Phase Ib Study to Evaluate RO7198457, an Individualized Neoantigen Specific Immunotherapy (iNeST), in Combination with Atezolizumab in Patients with Locally Advanced or Metastatic Solid Tumors” (https://www.abstractsonline.com/pp8/#!/9045/presentation/11339).

June 23rd

Sarepta & Codiak Will Collaborate to Research & Develop Exosome-Based Therapeutics for Rare Diseases; Two-Year Global Research & Option Agreement Covers Up to Five Neuromuscular Targets; Codiak Eligible to Receive $72.5 Million in Up-Front Payments

On June 22, 2020, Sarepta Therapeutics, Inc. (NASDAQ:SRPT) (https://www.sarepta.com/), a leader in precision genetic medicine for rare diseases, and Codiak BioSciences, Inc., a company at the forefront of advancing engineered exosomes as a new class of biologic medicines, announced a global research and option agreement to design and develop engineered exosome therapeutics to deliver gene therapy, gene editing, and RNA technologies for neuromuscular diseases. The engineered exosome approach offers the potential to effectively deliver genetic therapeutics without triggering the adaptive immune response. The two-year agreement includes up to five neuromuscular targets. Codiak is eligible to receive up to $72.5 million in up-front and near-term license payments plus research funding. Sarepta is granted an option to any of the candidates developed pursuant to the research alliance. Exosomes are natural nanoparticles that serve, in part, as the body’s intercellular communication system, facilitating the transfer of a wide variety molecular payloads between cells. Exosomes provide a unique advantage as a targeted delivery system for genetic medicines because they are believed to be inherently non-immunogenic. Through its proprietary, engEx Platform, Codiak can engineer exosomes with specific cargos and guide tropism to cell types of interest. The collaboration will leverage Codiak’s exosome engineering capabilities with Sarepta’s expertise in precision genetic medicine to develop next-generation therapeutics for patients with neuromuscular diseases that have few or no treatment options. “As Sarepta expands its leadership position in precision genetic medicine, this alliance with Codiak furthers our goal to deliver the most advanced therapies to patients.

June 22nd

AACR Honors MIT’s Tyler Jacks, PhD, with 2020 Princess Takamatsu Memorial Lectureship for His Remarkable Advancement of Genetically Engineered Mouse Models and for His Seminal Discoveries Related to Oncogenes and Immune System Regulation of Tumor Progress

On May 29, 2020, the American Association for Cancer Research (AACR) announced that it is recognizing Tyler Jacks, PhD, Fellow of the AACR Academy, with the 2020 AACR Princess Takamatsu Memorial Lectureship. Dr. Jacks is Director of the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT), Co-Director of the Ludwig Center at MIT, and a Howard Hughes Medical Institute (HHMI) Investigator. He is being recognized for transforming cancer research and the development of therapeutic treatments through his remarkable advancement of genetically engineered mouse models and for his seminal discoveries related to oncogenes, tumor suppressor genes, cell death, and immune system regulation of tumor progression. “Dr. Jacks is a highly esteemed cancer scientist, and we are delighted to recognize his exceptional body of innovative work,” said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. “His ground-breaking research has provided deep insights into cancer initiation and progression, and has led to the identification of promising new treatments for cancer patients worldwide. He is revered for his tremendous research achievements as well as for his commitment to collaborative research across the world.

Michael Karin, PhD, Honored with 2020 AACR-G.H.A. Clowes Award for Outstanding Basic Cancer Research; Dr. Karin Carried Out Seminal Research Connecting Inflammation & Cancer, Establishing Basis for Use of Anti-Cytokine and Anti-Inflammatory Drug Vs Cancer

On June 5, 2020, the American Association for Cancer Research (AACR) announced that it is honoring Michael Karin, PhD, Fellow of the AACR Academy, with the 2020 AACR-G.H.A. Clowes Award for Outstanding Basic Cancer Research. Dr. Karin (photo) (https://profiles.ucsd.edu/michael.karin), Distinguished Professor of Pharmacology and Pathology at the University of California(UC) San Diego School of Medicine, is being recognized for unraveling the role of metabolic stress, inflammation, and immunosuppression in cancer by establishing the tumorigenic function of NF-κB in cancer progenitors and myeloid cells, and for explaining how inflammation and cancer are linked, laying down the basis for use of anti-cytokine and anti-inflammatory drugs in cancer prevention and treatment. The AACR-G.H.A. Clowes Award for Outstanding Basic Cancer Research (https://www.aacr.org/awards/aacr-g-h-a-clowes-award/) was established by the AACR and Eli Lilly and Co., in 1961 to honor Dr. G.H.A. Clowes (https://en.wikipedia.org/wiki/George_Henry_Alexander_Clowes), who was a founding member of the AACR and a research director at Eli Lilly. The award is intended to recognize an individual who has made outstanding recent accomplishments in basic cancer research. Dr. Karin is world-renowned for his seminal research establishing the relationship between chronic inflammation and cancer, particularly colorectal cancer. He discovered that members of the IL-6 family of cytokines are capable of activating oncogenic transcription factors such as STAT3, resulting in colorectal and liver cancer onset. He also showed that IkB kinase contributes to colon, liver, and prostate cancer by activating NF-κB and its downstream expression of anti-apoptotic and growth-promoting genes. Dr.

June 22nd

AACR Honors St. Jude’s James R. Downing, MD, with Inaugural AACR-St. Baldrick’s Foundation Award for Outstanding Achievement in Pediatric Cancer Research

On June 22, 2020, the American Association for Cancer Research (AACR) presented the first-ever AACR-St. Baldrick’s Foundation Award for Outstanding Achievement in Pediatric Cancer Research to St. Jude Children’s Research Hospital Chief Executive Officer James R. Downing, MD. Dr. Downing (https://www.stjude.org/directory/d/james-downing.html) is also the director of the Molecular Pathology Laboratory at St. Jude Children’s Research Hospital and holds the Donald Pinkel Chair of Childhood Cancer Treatment. Dr. Downing is one of the most esteemed pediatric cancer researchers in the world. With this award, he is being recognized for his revolutionary research efforts dedicated to characterizing the genomics of pediatric cancer to inform the development of better treatments for children afflicted with cancer and for contributing to the creation and implementation of the Pediatric Cancer Genome Project (https://www.stjude.org/research/pediatric-cancer-genome-project.html), which has led to a number of landmark discoveries in the biology of brain tumors, leukemia, cancer of the peripheral nervous system, and tumors of the eye. The AACR-St. Baldrick’s Foundation Award for Outstanding Achievement in Pediatric Cancer Research (https://www.aacr.org/awards/aacr-st-baldricks-foundation-award-for-outst...) was established in 2019 to recognize major research discoveries in pediatric cancer research and to honor an individual who has significantly contributed to any area of pediatric cancer research, resulting in the fundamental improvement of the understanding and/or treatment of pediatric cancer.

June 21st

AACR Honors Patricia S. Steeg with 2020 Women in Cancer Research Charlotte Friend Lectureship Award, Recognizing Her Ground-Breaking Research on Breast Cancer Metastasis, Including Discovery of the First Metastasis Suppressor Gene (NME)

On June 16, 2020, the American Association for Cancer Research (AACR) announced that it is honoring Patricia S. Steeg, PhD, with the 2020 AACR-Women in Cancer Research Charlotte Friend Memorial Lectureship award. Dr. Steeg, Co-Director of the Office of Translational Resources and Associate Director of the Center for Cancer Research at the National Cancer Institute (NCI), is being recognized for her ground-breaking research on breast cancer metastasis, including the discovery of the first metastasis suppressor gene and development of a clinical-translational program dedicated to investigating brain metastases of breast cancer. The AACR-Women in Cancer Research Charlotte Friend Lectureship (https://www.aacr.org/awards/aacr-women-in-cancer-research-charlotte-frie...) was established in 1998 in honor of renowned virologist and discoverer of the Friend virus, Charlotte Friend, PhD, for her pioneering research on viruses, cell differentiation, and cancer. This lectureship recognizes an outstanding female or male scientist who has made meritorious contributions to the field of cancer research and who has, through leadership or by example, furthered the advancement of women in science. Dr. Steeg is best known for performing pioneering research on breast cancer metastasis. In 1988, she discovered the first metastasis suppressor gene, nm23 (NME). Her work demonstrated that the previously unknown NME gene is commonly down-regulated in cells with increased metastatic potential. Dr. Steeg later cloned the NME family of genes and further characterized the biological and enzymatic activities of NME by conducting experiments in which she reintroduced NME into metastatic tumor cells.

Israel Company Kamada Announces Availability of Its Plasma-Derived Hyperimmune IgG Therapy for Compassionate Use Treatment of COVID-19 Infection in Israel

On June 17, 2020, Kamada Ltd. (NASDAQ: KMDA; TASE: KMDA.TA), a plasma-derived-biopharmaceutical company headquartered in Rehovot, Israel, provided an update on its development of a plasma-derived immunoglobulin G (IgG) product for coronavirus 2019 (COVID-19) disease. Kamada (https://www.kamada.com/) completed manufacturing of the first batch of its plasma-derived IgG product for COVID-19, utilizing the Company’s approved proprietary IgG platform technology, and additional production is ongoing. The initial vials are available for compassionate use in Israel. In addition, Kamada’s proposed clinical protocol for a Phase 1/2 clinical trial was submitted to the Israeli Ministry of Health, and the Company expects to initiate the study during the third quarter of this year. In order to expand its clinical development program to the U.S., Kamada, with the support of Kedrion Biopharma (https://www.kedrion.us/), intends to conduct a pre-Investigational New Drug (pre-IND) meeting with the U.S. Food and Drug Administration (FDA) early in the third quarter in order to obtain FDA’s acceptance of the proposed clinical development program. Pursuant to the company’s global collaboration agreement with Kedrion for the development, manufacturing, and distribution of the plasma-derived IgG product for COVID-19, Kedrion is currently collecting COVID-19 convalescent plasma from U.S. recovered patients that will be used by Kamada to manufacture additional batches of the product. Kedrion is collecting the plasma, through its plasma business unit, KEDPLASMA, at 23 FDA-approved centers across the United States. “We are extremely pleased with the rapid and important progress achieved to date in advancing our plasma-derived IgG product for COVID-19,” said Amir London, Kamada’s Chief Executive Officer.