Science
Welcome to another episode of Biotechnology Focus radio. I am your host – Michelle Currie – here to give you the rundown on the Canadian biotech scene! Coming up we have some inspiring research from the University of Alberta regarding viral pathogen treatment; McMaster researchers have a new hypothesis on Huntington’s Disease; RepliCel solidifies co-development deal in Greater China; scientists discover a way to genetically screen for acute myeloid leukemia; and putting Canada in the limelight when it comes down to artificial intelligence and deep learning. Keep on listening to find out more of the details! +++++ The University of Alberta appears to have hit the nail on the head yet again. With so much inspiring research coming out of this campus, it should come as no surprise that they have made a significant discovery that has the potential to treat viral pathogens such as the Zika virus and respiratory syncytial virus (RSV). Scientists from UofA discovered a new and promising class of chemical compounds that is comparable to the naturally occurring isatisine A, an antiviral originally found in traditional Chinese herbal medicine. Fred West, a professor in the Department of Chemistry, who led the discovery along with RSV researcher David Marchant, a professor in the Department of Medical Microbiology and Immunology, says, “This is both a remarkable scientific discovery and also something that has the potential to positively affect not only global health but also the economy of Canada.” West and Marchant worked in conjunction with Zika expert and cell biologist Tob Hobman, who is also a professor in the Faculty of Medicine & Dentistry at the University of Alberta. They tested the compound against potent viruses, such as Zika and respiratory syncytial virus , that yielded remarkable results. The compound was active and effective against both viral infections. The Zika virus, which is a mosquito-borne pathogen, began wreaking havoc in May of 2015 after it had been identified as the culprit behind an outbreak of prenatal defects across South America. It coincided with a 2,700 per cent increase in Brazil from reported cases of microcephaly, an often fatal congenital condition associated with incomplete brain development in newborns. Whereas, relatively unheard of respiratory syncytial virus poses a greater threat to infants, the elderly and those with compromised immune systems. This virus is responsible for up to 30 per cent of hospitalized respiratory cases in any given year. West adds, “What we aim to do is further refine this compound to keep the elements that make it medically active and build in the structural components that make it possible for patients to consume in drug form. We are approaching that point.” The next stage of drug development is already underway, and with Marchant’s new company Antibiddes Technologies Inc. ready to license the intellectual property and begin commercialisation, this is a promising development that could change the face of viral pathogen treatment. ++++++ McMaster researchers develop a new theory regarding Huntington’s Disease that may shape the future of drug development for the disease. A team of researchers from the university found that a unique type of signalling found in damaged DNA signals huntingtin – a harmful mutant protein found in the genes of those diagnosed with Huntington’s Disease – to aid in DNA repair is defective for those with the condition. The new hypothesis was published in the Proceedings of the National Academy of Science (PNAS). Laura Bowie, a PhD student in the Department of Biochemistry and Biomedical Sciences at McMaster, says, “The concept was that if we applied the signalling molecule back in excess, even orally, this signalling can be restored in the Huntington’s disease mouse brain. The net result was that we fixed the modification of huntingtin not seen in mutant huntingtin in Huntington’s disease.” Using this hypothesis, the study team discovered a molecule called N6-furfuryladenine, derived from the repair of DNA damage, which corrected the defect seen in mutant huntingtin. “Based on dosing by different ways of this molecule in mouse Huntington’s disease models, Huntington’s disease symptoms were reversed,” says Bowie. “The mutant huntingtin protein levels were also restored to normal, which was a surprise to us.” Ray Truant, senior author on the study, has dedicated his career to Huntington’s disease research and how mutation leads to Huntington’s disease. It was his lab that was the first to demonstrate that normal huntingtin was involved in DNA repair. Truant argues that the traditional and controversial amyloid/protein misfolding hypothesis, where a group of proteins stick together forming brain deposits, is likely the result of the disease, rather than its cause. He also stated that he considers this paper the most significant of his career, and that “This is an important new lead and a new hypothesis, but it is important for people to know this is not a drug or cure. This is the first new hypothesis for Huntington’s disease in 25 years that does not rely on the version of the amyloid hypothesis which has consistently failed in drug development for other diseases.” Huntington’s Disease is an inherited, neurodegenerative illness that comes with dire physical, cognitive and emotional symptoms that often hit around middle age. The mutant huntingtin protein causes certain parts of the brain to die – specifically the caudate, the putamen and, as the disease progresses, the cerebral cortex. Bev Heim-Myers, CEO of the Huntington Society of Canada adds “Innovative research initiatives, such as the work led by the team in Dr. Truant’s lab, including PhD student Laurie Bowie, has the potential to transform HD research. The answers we find for Huntington’s disease will likely lead to better understanding of treatments for other neurological diseases and it is important that we continue this cross-talk amongst neurodegenerative diseases.” The study was conducted in partnership with the University of Alberta, Western University, Johns Hopkins University, and a collaboration with a U.S. biotech firm, Mitokinin LLC. Their work now continues in developing better derivatives of N6-furfuryladenine towards developing a drug. This study was funded by the Canadian Institutes of Health Research, the Krembil Foundation, and the Huntington Society of Canada. +++++ Vancouver-based Replicel Life Sciences announces that they have signed definitive agreements with YOFOTO, a Chinese company, solidifying their partnership to commercialise three of Replicel’s programs in Greater China. The collaboration focuses on the development and commercialization in Greater China of RepliCel’s tendon regeneration cell therapy (RCT-01), skin rejuvenation cell therapy (RCS-01), and its injection technology in development for dermal applications (RCI-02) (excluding hair-related treatments). YOFOTO Chairman states, “YOFOTO is a fast-growing company built on values related to beauty and healthy, active lifestyles. As a key part of developing and commercializing products related to these core values for our consumers, we are committed to being a leader in China in the commercialization of regenerative medicines. The RepliCel cell therapy and injection technologies focused on skin rejuvenation and tendon repair are important building blocks in YOFOTO’s strategic healthcare vision. We are pleased to have structured a deal with RepliCel which results in YOFOTO not only being a development partner and commercial licensee but also an investor committed to contributing to RepliCel’s global success.” YOFOTO’s investment in Replicel will include milestone payments, minimum program funding commitments, and sales royalties in exchange for an exclusive 15-year license to three of RepliCel products for Greater China (Mainland China, Hong Kong, Macau, and Taiwan). Additionally, YOFOTO commits to spending a minimum of C$7 million on Replicel’s programs and associated cell processing manufacturing facility over the next five years in Greater China. RepliCel president & CEO, Lee Buckler says, “In 2017 RepliCel delivered successful phase I data in all three of its cell therapy programs and functioning prototypes of its next-generation dermal injector,” says “We were committed to delivering a landmark partnership to RepliCel shareholders in 2018. The partnership with YOFOTO represents such a deal and provides RepliCel with not only an outstanding partner in Greater China but capital to move our programs forward in Europe and North America,” he adds. The deposit of over $5 million has been paid by YOFOTO, but remains in escrow following the closing of the transaction. Once YOFOTO has met certain conditions and once relevant Chinese patents are issued in China, they will be assigned a YOFOTO-owned Canadian subsidiary. This is very exciting news for Replicel and Canada alike, as Canadian biotech companies begin to spread across the Pacific, with more foreign companies seeking to invest in Canadian innovation and research. +++++ An international team of scientists discovers a technique that predicts healthy individuals who are at risk of developing acute myeloid leukemia (AML), which is an aggressive and often deadly form of blood cancer. The findings, published in Nature, illuminate the ‘black box of leukemia’ and answer the question of where, when and how the disease begins, says co-principal investigator Dr. John Dick, Senior Scientist at Princess Margaret Cancer Centre, University Health Network. Dr. Dick, who is a professor, Department of Molecular Genetics, University of Toronto, holds the Canada Research Chair in Stem Cell Biology, and is co-leader of the Acute Leukemia Translational Research Initiative at the Ontario Institute for Cancer Research, says, “We have been able to identify people in the general population who have traces of mutations in their blood that represent the first steps in how normal blood cells begin on a pathway of becoming increasingly abnormal and puts them at risk of progressing to acute myeloid leukemia. We can find these traces up to 10 years before acute myeloid leukemia actually develops. This long-time window gives us the first opportunity to think about how to prevent acute myeloid leukemia.” Study author Dr. Sagi Abelson, a post-doctoral fellow in the Dick lab, says: “acute myeloid leukemia is a devastating disease diagnosed too late, with a 90 per cent mortality rate after the age of 65. Our findings show it is possible to identify individuals in the general population who are at high risk of developing acute myeloid leukemia through a genetic test on a blood sample. The ultimate goal is to identify these individuals and study how we can target the mutated blood cells long before the disease actually begins.” The study stems from Dr. Dick’s 2014 discovery that a pre-leukemic stem cell could be found hiding amongst all the leukemia cells that are present in the blood sample taken when a person is first diagnosed with acute myeloid leukemia. The pre-leukemic stem cell still functions normally but it has taken the first step in generating pathway of cells that became more and more abnormal resulting in acute myeloid leukemia (Nature, February 12, 2014). Dr. Dick says, “Our 2014 study predicted that people with early mutations in their blood stem cells, long before the disease appears and makes them sick, should be able to be detected within the general population by testing a blood sample for the presence of the mutation.” The team extracted the data from more than 100 participants who developed acute myeloid leukemia six to 10 years after joining the study, plus the data from an age-matched cohort of more than 400 who did not develop the disease. Dick adds, “We wanted to know if there was any difference between these two groups in the genetics of their ‘normal’ blood samples taken at enrollment. To find out, we developed a gene sequencing tool that captured the most common genes that get altered in acute myeloid leukemia and sequenced all the 500 blood samples.” The gene sequencing tool was a success and picked up mutations years before an individual was diagnosed with acute myeloid leukemia to accurately predict those at risk. Moreover, the team used advanced computational technology to assay the information obtained from routinely collected blood tests taken over 15 years in Israel and housed in a massive database of 3.4 million electronic health records. The study has linked acute myeloid leukemia with a common feature of aging called ARCH-age related clonal hematopoiesis, whereby blood stem cells acquire mutations and become a little more proliferative. The majority of people that have ARCH will not develop acute myeloid leukemia. It is a requirement to have acute myeloid leukemia, but not the other way around. +++++ Machine learning is augmenting human ability and drastically changing possibilities. It is restructuring businesses and rewiring brains for transformative thinking. Whether it be to develop vaccines for deadly diseases or combat climate change, Canada is at the forefront of this monumental shift. Canada has been on the vanguard of machine learning long before it became a popular headline. The growth and brilliant minds from around the country have led the way for Canada to place its mark with AI on the world and build a more promising ecosystem for the future. Across the country, there have been several companies lending a hand in this newer and multi-faceted industry that will reshape history. Among those, innovative researchers are developing imaging devices for skin cancer, diagnostic platforms that analyse natural speech to detect dementia and mental decline, advanced signal analysis to diagnose coronary artery disease, just to name a few, and numerous others that stem to topics unrelated to health care, but keep Canada at the forefront of change. This year Canada had its 31st Canadian Conference in Artificial Intelligence that stands to show how long Canada has been involved with this game-changing technology. Events like this bring together hundreds of leaders in research, industry, and government that provide a melting pot of inquisitive and like-minded people. Life sciences is an industry that is filled with innovation and offers much economic promise for governments who desire to grow a knowledge-based economy. Therefore, Biotechnology Focus, in support of Global Biotech Week, is conducting a survey to gauge Canada’s innovation culture. The results will be featured in a special report in the September issue. The report will highlight trends, identify areas of strengths that can be leveraged as well as opportunities for improvement to support growth for the Canadian life sciences industry. Artificial intelligence and deep learning have the potential to revolutionize healthcare, and with Canada as a global frontrunner, we can expect to see exponential shifts in the upcoming years to come. Add your voice to the survey at https://www.surveymonkey.com/r/BioFocus2018. ++++++ Well, that wraps up another episode of Biotechnology Focus radio! Thanks for tuning in! And let’s remember that with Canada in the limelight it is important for everybody in the life sciences industry to make their voice heard, so please fill out the quick innovation survey so we can continue to enhance this spectacular industry and elevate health care. Until next time, from my desk to yours – this is Michelle Currie.