On January 2, 2018 AgeX Therapeutics, Inc. (AgeX), a subsidiary of BioTime, Inc. (NYSE American: BTX), reported a newly-published peer-reviewed study that reveals genes implicated in tissue regeneration, cancer, and aging (Press release, BioTime, JAN 2, 2018, View Source;p=RssLanding&cat=news&id=2324347 [SID1234522796]). The study, by scientists at AgeX and BioTime, in collaboration with Insilico Medicine, utilized artificial intelligence (AI) technology to parse millions of gene expression data points to decipher the complex mechanisms controlling natural tissue regeneration. The results, published in the peer-reviewed scientific journal Oncotarget, showed that the candidate genes are expressed differently in tissues early in development when they are capable of regeneration compared to later in life when regeneration can no longer take place. Surprisingly, some of the genes, including one highlighted in the study, COX7A1, displayed a rare profile of being nearly universally dysregulated in diverse types of cancer. The discoveries may lead to novel strategies to induce Tissue Regeneration (iTRTM) in the context of trauma or age-related degenerative disease, as well as treat and diagnose cancer.
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"It is rare to find genes implicated in tissue regeneration, let alone with abnormal expression in so many diverse cancer types such as those of the breast, lung, kidney, bone, and muscle," said Michael D. West, PhD, CEO of AgeX and co-CEO of BioTime. "AgeX has certain rights to use the associated patent applications and to commercialize related therapeutic and diagnostic applications. Since we believe unlocking the natural ability of the human body to regenerate tissues afflicted with degenerative disease is a very large market opportunity, we are aggressively developing products using the technology."
A short video is available online describing the discovery and its implication for product development at AgeX. Included in the video is a discussion of an iTR product designated RenelonTM, which, in its first generation form, utilizes a repurposed drug and may therefore have a relatively short development timeline.
"The embryonic-to-fetal transition (EFT) deciphered in this study is emerging as a wonderful new arena in which to explore the enhancement of regenerative capacity in old age, which is the core of AgeX’s mission," said Aubrey de Grey, PhD, VP of New Technology Discovery at AgeX. "The discovery of a subunit of the respiratory chain as a key EFT marker dovetails this research fascinatingly with age-related changes in mitochondrial function, which have long been a priority in the anti-aging field and in my own work."
"BioTime and AgeX Therapeutics are at the forefront of regenerative medicine," commented Alex Zhavoronkov, PhD, CEO of Insilico Medicine. "By utilizing their heavy investment in large-scale, highly-controlled experiments and their unique expertise in regenerative medicine we managed to develop the AI-powered system for cell and tissue sample profiling. We utilized this system to identify the important genes implicated in the EFT, and possibly in aging. This collaboration started in 2015 when deep leaning methods were in their infancy and required two years to diligently validate the outcomes. We learned that domain expertise is just as important as expertise in AI."
Background on Induced Tissue Regeneration
The leading unsolved problem in medicine as the year 2018 arrives remains the inability of the adult human body to regenerate tissues affected by injury or disease. It is estimated that approximately 80% of the nearly $3 trillion annual health care expenditures in the United States can be attributed to chronic disease. The chronic degenerative diseases of aging are also on the rise due to the aging of the 76 million post-WWII baby boom population. AgeX is focused on developing breakthrough technology platforms to directly address some of the largest markets associated with this demographic. One such platform is induced Tissue Regeneration (iTR), the subject of today’s scientific publication.
Adult humans, like most mammals, have only a limited capacity to repair tissues in the body resulting from trauma or degenerative disease. However, in some species, such as the Mexican salamander, there exists a profound capacity to regenerate injured tissues, even amputated limbs. Recent studies suggest that this power reflects a capacity present early in life and largely lost by the time we are born.
Using the Company’s proprietary pluripotent stem cell-based platform, AgeX and BioTime scientists compared cells with the potential to regenerate tissue in humans, similar to that occurring in naturally regenerating animals, with adult cells lacking the capacity. The transition from an embryonic capacity to regenerate tissue to the subsequent loss in adults (replaced by scarring rather than regenerating) is one of the most complex processes studied in biology today. Therefore, AgeX scientists collaborated with Insilico Medicine to apply machine intelligence to better understand the process. A computer-based analytical tool designated "Embryonic.AI" resulting from this AI research is available online at AgeX database LifeMap Discovery.
The study resulted in the identification of genes differently expressed during the time tissues can regenerate compared to later in life when that capacity is impaired. One gene highlighted in the study is designated COX7A1 which is thought to play a role in energy metabolism along with other critical functions in the cell. Consistent with a role of COX7A1 in regeneration and cancer, the gene appeared to be profoundly dysregulated in a broad array of cancer cell types, suggesting cancer may be thought of as "regeneration out of control." As a result, the discoveries reported in today’s publication may have the potential to lead to the ability to induce scarless tissue regeneration in humans, as well as point to new strategies for the diagnosis and treatment of cancer.
The publication titled "Use of deep neural network ensembles to identify embryonic-fetal transition markers: repression of COX7A1 in embryonic and cancer cells" (Oncotarget, December 2017, in press, View Source included Michael D. West, Ivan Labat, Hal Sternberg, and Dana Larocca of AgeX; Igor Nasonkin and Ratnesh Singh of BioTime; Karen B. Chapman and Evgeny Izumchenko of Johns Hopkins University; Karen Copeland of Boulder Statistics; and Eugene Makarev, Alex Aliper, Andrey Kazennov, Andrey Alekseenko, Nikolai Shuvalov, Evgenia Cheskidova, Aleksandr Alekseev, Artem Artemov, Evgeny Putin, Polina Mamoshina, Nikita Pryanichnikov, Ksenia Lezhnina, Mikhail Korzinkin, and Alex Zhavoronkov of Insilico Medicine.