BioViva

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BioViva is an American biotechnology gene therapy company, based in Bainbridge Island, Washington, researching treatments to interfere in the aging process in humans. [1]

Contents

BioViva
Founded2015;9 years ago (2015)
Headquarters Bainbridge Island, Washington,
United States

History

BioViva was founded in 2015. [2] The CEO, Liz Parrish, started the company by becoming the first person in human history to take gene therapies associated with lengthening lifespans in model organism, [3] she appeared at WIRED Health 2017 in London to discuss BioViva's testing of gene therapies targeting hallmarks of the ageing process. She stated, "The company was built essentially to prove these therapies work or not." [4] Since then the company has gone into research and development and patented AAV based gene therapies [5] and launched a new gene therapy platform with CMV as the vector. [6] Parrish stated there was no other way to protect people's rights to new medicine in a recent talk in India at the Synapse Conference. [7]

Responses to Parrish using herself as first experimental subject

Parrish's decision to be 'patient zero' and test the company's technology on herself in a personalized N=1 study was a response to her son's diagnosis of Type 1 Diabetes. After finding no curative course Parrish looked into genetics. She claims that every gene BioViva targets will also treat a childhood disease. [8] Dr. Lawrence Altman, author of Who Goes First? The Story of Self-Experimentation in Medicine has said, "N's of 1 have had their value through history, and will. But you're not going to license a drug based on an N-of-1." [9] Her treatment, labelled as self-experimentation, was highly controversial. Though controversial, Dr Barry Marshall went on to win a Nobel prize for such an effort in the treatment of stomach ulcers. [10] As the requirements to progress to human trials had not started, the US Food and Drug Administration did not authorize Parrish's experiments. Parrish traveled to Colombia for the treatments. [11]

In 2016 some initially criticized BioViva's release of data claiming an extension of Parrish's leukocyte telomeres following her therapy, stating that the aforementioned extension is within the error change for telomere measurements. Dr. Bradley Johnson, Associate Professor of Pathology and Lab Medicine at the University of Pennsylvania said, "Telomere length measurements typically have low precision, with variation in measurements of around 10 percent, which is in the range of the reported telomere lengthening apparently experienced by Elizabeth Parrish." [12] In 2022 BioViva released a peer reviewed paper that showed lengthening of telomeres over years and the press has changed mass scientific opinion in the company's favor [13]

The Hallmarks of Aging papers seems to have created a platform in which to launch BioViva's gene therapies as their targets are these hallmarks. [14] [15] Telomeres were once thought oncogenic or cancer causing, but both María Blasco and BioViva added to evidence that it does not increase cancer risk in model organisms. [16] The telomeres' function is to maintain chromosomal integrity and provide a substrate for DNA replication (thereby allowing for cellular multiplication), however, telomere shortening causes shortening of cellular lifetime which helps to avoid cancerous mutations in cells. Duncan Baird, a professor of Cancer and Genetics at Cardiff University's School of Medicine, states, "Meddling with a fundamentally important tumor-suppressive mechanism that has evolved in long-lived species like ours doesn't strike me as a particularly good idea." [11]

George M. Martin, Professor of Pathology at the University of Washington had agreed to be an adviser to the company but resigned upon hearing about Parrish's self-experiments. [11] But other advisors for BioViva have stayed, including Prof George Church of Harvard who has continued to advocate for the company and has showed BioViva's most recent data in several virtual talks as of 2024 [17]

In 2015, Antonio Regalado, a reporter for the MIT Technology Review states, "The experiment seems likely to be remembered as either a new low in medical quackery or, perhaps, the unlikely start of an era in which naive people receive genetic modifications not just to treat disease, but to reverse aging." [18] Regalado seems to have changed his mind and reversed his criticism, he has sense written several articles in support of the science. Since then several of the biggest companies and a few billionaires have started on the same pursuit including Jeff Bezos multi billion dollar endeavor called Altos and Google's anti-aging company called Calico.

Research

BioViva's research interests are based on preclinical research of both the enzyme telomerase and inhibition of myostatin, Klotho, FGF21, and PGC-1a, all of which Parrish claims to have taken. [19] BioViva since has expanded its interest to platform technology to deliver any of the multitude of gene that extend lifespans in model organism

BioViva's research using it's proprietary CMV gene therapy vector they were able to increase in life extension of 42% for a telomerase inducing gene therapy and 32% for a follistatin inducing gene therapy The gene therapy was also re-dosable. [20] Telomerase gene therapy utilizing an adeno-associated virus at the Spanish National Cancer Research Centre (CNIO), has demonstrated several beneficial effects and an increase in median lifespan of up to 24% in mice. [21] [22] [23] [24] Discussing her team's research, María Blasco stated in discussion with The Scientist, "We demonstrated that AAV9-Tert gene therapy was sufficient to delay age-related pathologies and extend both median and maximum longevity in mice. Many pathologies were delayed, including cancer. Translating these results to human diseases (telomere syndromes or certain age-related diseases without effective treatments) may be of interest in the context of clinical trials approved by the corresponding regulatory agencies. [25] However, some experts draw attention that the results of studies in mice cannot always be directly transferred to humans. [26]

In 2021. BioViva again came under media interest in there involvement of assessing data of a human investigator lead study for dementia. [27] This nonprofit funded trial was the first in human use for gene therapy for dementia with suspected Alzheimer's Disease. Defending the decision, Parrish claimed that it is essential for data to be collected on offshore trials for the betterment of patients, BioViva was given the patent for assessing this data. Parrish says the patent is pending. [28]

Related Research Articles

<span class="mw-page-title-main">Telomere</span> Region of repetitive nucleotide sequences on chromosomes

A telomere is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Telomeres are a widespread genetic feature most commonly found in eukaryotes. In most, if not all species possessing them, they protect the terminal regions of chromosomal DNA from progressive degradation and ensure the integrity of linear chromosomes by preventing DNA repair systems from mistaking the very ends of the DNA strand for a double-strand break.

Senescence or biological aging is the gradual deterioration of functional characteristics in living organisms. Whole organism senescence involves an increase in death rates or a decrease in fecundity with increasing age, at least in the later part of an organism's life cycle. However, the resulting effects of senescence can be delayed. The 1934 discovery that calorie restriction can extend lifespans by 50% in rats, the existence of species having negligible senescence, and the existence of potentially immortal organisms such as members of the genus Hydra have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.

<span class="mw-page-title-main">Telomerase</span> Telomere-restoring protein active in the most rapidly dividing cells

Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes. Telomeres protect the end of the chromosome from DNA damage or from fusion with neighbouring chromosomes. The fruit fly Drosophila melanogaster lacks telomerase, but instead uses retrotransposons to maintain telomeres.

Biological immortality is a state in which the rate of mortality from senescence is stable or decreasing, thus decoupling it from chronological age. Various unicellular and multicellular species, including some vertebrates, achieve this state either throughout their existence or after living long enough. A biologically immortal living being can still die from means other than senescence, such as through injury, poison, disease, predation, lack of available resources, or changes to environment.

<span class="mw-page-title-main">Hayflick limit</span> Limit to divisions of a normal human cell

The Hayflick limit, or Hayflick phenomenon, is the number of times a normal somatic, differentiated human cell population will divide before cell division stops.

Enquiry into the evolution of ageing, or aging, aims to explain why a detrimental process such as ageing would evolve, and why there is so much variability in the lifespans of organisms. The classical theories of evolution suggest that environmental factors, such as predation, accidents, disease, and/or starvation, ensure that most organisms living in natural settings will not live until old age, and so there will be very little pressure to conserve genetic changes that increase longevity. Natural selection will instead strongly favor genes which ensure early maturation and rapid reproduction, and the selection for genetic traits which promote molecular and cellular self-maintenance will decline with age for most organisms.

<span class="mw-page-title-main">Eternal youth</span> Physical immortality free of ageing

Eternal youth is the concept of human physical immortality free of ageing. The youth referred to is usually meant to be in contrast to the depredations of aging, rather than a specific age of the human lifespan. Eternal youth is common in mythology, and is a popular theme in fiction.

<span class="mw-page-title-main">Carol W. Greider</span> American molecular biologist and Nobel laureate

Carolyn Widney Greider is an American molecular biologist and Nobel laureate. She joined the University of California, Santa Cruz as a Distinguished Professor in the department of molecular, cell, and developmental biology in October 2020.

<span class="mw-page-title-main">Telomerase reverse transcriptase</span> Catalytic subunit of the enzyme telomerase

Telomerase reverse transcriptase is a catalytic subunit of the enzyme telomerase, which, together with the telomerase RNA component (TERC), comprises the most important unit of the telomerase complex.

<span class="mw-page-title-main">Telomerase RNA component</span> NcRNA found in eukaryotes

Telomerase RNA component, also known as TR, TER or TERC, is an ncRNA found in eukaryotes that is a component of telomerase, the enzyme used to extend telomeres. TERC serves as a template for telomere replication by telomerase. Telomerase RNAs differ greatly in sequence and structure between vertebrates, ciliates and yeasts, but they share a 5' pseudoknot structure close to the template sequence. The vertebrate telomerase RNAs have a 3' H/ACA snoRNA-like domain.

Telomere-binding proteins function to bind telomeric DNA in various species. In particular, telomere-binding protein refers to TTAGGG repeat binding factor-1 (TERF1) and TTAGGG repeat binding factor-2 (TERF2). Telomere sequences in humans are composed of TTAGGG sequences which provide protection and replication of chromosome ends to prevent degradation. Telomere-binding proteins can generate a T-loop to protect chromosome ends. TRFs are double-stranded proteins which are known to induce bending, looping, and pairing of DNA which aids in the formation of T-loops. They directly bind to TTAGGG repeat sequence in the DNA. There are also subtelomeric regions present for regulation. However, in humans, there are six subunits forming a complex known as shelterin.

<span class="mw-page-title-main">Cycloastragenol</span> Chemical compound

Cycloastragenol is a triterpenoid isolated from various legume species in the genus Astragalus that is purported to have telomerase activation activity. A preliminary in vitro study on human CD4 and CD8 T cells found that cycloastragenol may moderately increase telomerase activity and inhibit the onset of cellular senescence.

William Henry Andrews is an American molecular biologist and gerontologist whose career is centered on searching for a cure for human aging. Andrews is the founder and president of the biotechnology company Sierra Sciences. In the 1990s, he led the team at Geron Corporation that was the first to successfully identify the genes for human enzyme telomerase. This enzyme is responsible for preventing telomeres from shortening in human primordial germ cells.

Shelterin is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as to regulate telomerase activity. In mammals and other vertebrates, telomeric DNA consists of repeating double-stranded 5'-TTAGGG-3' (G-strand) sequences along with the 3'-AATCCC-5' (C-strand) complement, ending with a 50-400 nucleotide 3' (G-strand) overhang. Much of the final double-stranded portion of the telomere forms a T-loop (Telomere-loop) that is invaded by the 3' (G-strand) overhang to form a small D-loop (Displacement-loop).

<span class="mw-page-title-main">Genetics of aging</span> Overview of the genetics of aging

Genetics of aging is generally concerned with life extension associated with genetic alterations, rather than with accelerated aging diseases leading to reduction in lifespan.

<span class="mw-page-title-main">María Blasco Marhuenda</span> Spanish molecular biologist (born 1965)

María Antonia Blasco Marhuenda, known as María Blasco, is a Spanish molecular biologist. She is the current director of the Spanish National Cancer Research Centre.

Life Length is a biotechnology company. Located in Madrid, it provides telomere diagnostics as well as telomerase measurement.

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. The hallmarks of aging are the types of biochemical changes that occur in all organisms that experience biological aging and lead to a progressive loss of physiological integrity, impaired function and, eventually, death. They were first listed in a landmark paper in 2013 to conceptualize the essence of biological aging and its underlying mechanisms.

This timeline lists notable events in the history of research into senescence or biological aging, including the research and development of life extension methods, brain aging delay methods and rejuvenation.

<span class="mw-page-title-main">Relationship between telomeres and longevity</span>

The relationship between telomeres and longevity and changing the length of telomeres is one of the new fields of research on increasing human lifespan and even human immortality. Telomeres are sequences at the ends of chromosomes that shorten with each cell division and determine the lifespan of cells. The telomere was first discovered by biologist Hermann Joseph Muller in the early 20th century. However, experiments by Elizabeth Blackburn, Carol Greider, and Jack Szostak in the 1980s led to the successful discovery of telomerase and a better understanding of telomeres.

References

  1. ↑ "Nature".
  2. ↑ "Company Overview of BioViva USA Inc". Bloomberg. Archived from the original on 2019-04-02. Retrieved November 14, 2016.
  3. ↑ Mohammadi, Dara; Davis, Nicola (24 July 2016). "Can this woman cure ageing with gene therapy?". The Observer.
  4. ↑ Medeiros, João. "Ageing is a disease. Gene therapy could be the 'cure'". Wired UK . Retrieved 31 March 2017.
  5. ↑ "Methods of treating or preventing age related disorders - Patent US-11266721-B1 - PubChem".
  6. ↑ Jaijyan, Dabbu Kumar; Selariu, Anca; Cruz-Cosme, Ruth; Tong, Mingming; Yang, Shaomin; Stefa, Alketa; Kekich, David; Sadoshima, Junichi; Herbig, Utz; Tang, Qiyi; Church, George; Parrish, Elizabeth L.; Zhu, Hua (17 May 2022). "New intranasal and injectable gene therapy for healthy life extension". Proceedings of the National Academy of Sciences. 119 (20): e2121499119. Bibcode:2022PNAS..11921499J. doi: 10.1073/pnas.2121499119 . PMC   9171804 . PMID   35537048.
  7. ↑ "Synapse - Home".
  8. ↑ "Gene Therapy to Engineer Healthy Longevity | Liz Parrish | TEDxOxford". YouTube . 4 April 2019.
  9. ↑ "Biotech executives using themselves as human guinea pigs". STAT. 7 July 2016. Retrieved 2017-03-31.
  10. ↑ Watts, Geoff (8 October 2005). "Nobel prize is awarded to doctors who discovered H pylori". BMJ. 331 (7520): 795.1. doi:10.1136/bmj.331.7520.795. PMC   1246068 . PMID   16210262.
  11. 1 2 3 Nicola Davis; Dara Mohammadi (24 July 2016). "Can this woman cure ageing with gene therapy?". The Guardian. Retrieved 1 August 2016.
  12. ↑ "Liz Parrish Is Patient Zero in Her Own Anti-Aging Experiment - The Crux". The Crux. 2016-04-29. Retrieved 2017-03-31.
  13. ↑ "Home".
  14. ↑ López-Otín, Carlos; Blasco, Maria A.; Partridge, Linda; Serrano, Manuel; Kroemer, Guido (June 2013). "The Hallmarks of Aging". Cell. 153 (6): 1194–1217. doi:10.1016/j.cell.2013.05.039. PMC   3836174 . PMID   23746838.
  15. ↑ López-Otín, Carlos; Blasco, Maria A.; Partridge, Linda; Serrano, Manuel; Kroemer, Guido (January 2023). "Hallmarks of aging: An expanding universe". Cell. 186 (2): 243–278. doi:10.1016/j.cell.2022.11.001. PMID   36599349.
  16. ↑ Bernardes de Jesus, Bruno; Vera, Elsa; Schneeberger, Kerstin; Tejera, Agueda M.; Ayuso, Eduard; Bosch, Fatima; Blasco, Maria A. (August 2012). "Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer". EMBO Molecular Medicine. 4 (8): 691–704. doi:10.1002/emmm.201200245. PMC   3494070 . PMID   22585399.
  17. ↑ "Genome Engineering for Healthy Longevity – George Church at Longevity Summit Dublin 2023". YouTube . 26 September 2023.
  18. ↑ Regalado, Antonio (14 October 2015). "A Tale of Do-It-Yourself Gene Therapy". MIT Technology Review . Retrieved 25 July 2016.
  19. ↑ Yokoyama, Jennifer S.; Sturm, Virginia E.; Bonham, Luke W.; Klein, Eric; Arfanakis, Konstantinos; Yu, Lei; Coppola, Giovanni; Kramer, Joel H.; Bennett, David A.; Miller, Bruce L.; Dubal, Dena B. (March 2015). "Variation in longevity gene KLOTHO is associated with greater cortical volumes". Annals of Clinical and Translational Neurology. 2 (3): 215–230. doi:10.1002/acn3.161. PMC   4369272 . PMID   25815349.
  20. ↑ Jaijyan, Dabbu Kumar; Selariu, Anca; Cruz-Cosme, Ruth; Tong, Mingming; Yang, Shaomin; Stefa, Alketa; Kekich, David; Sadoshima, Junichi; Herbig, Utz; Tang, Qiyi; Church, George; Parrish, Elizabeth L.; Zhu, Hua (17 May 2022). "New intranasal and injectable gene therapy for healthy life extension". Proceedings of the National Academy of Sciences. 119 (20): e2121499119. Bibcode:2022PNAS..11921499J. doi: 10.1073/pnas.2121499119 . PMC   9171804 . PMID   35537048.
  21. ↑ "Telomeres and Telomerase Group". Spanish National Cancer Research Centre. 19 May 2008. Archived from the original on 3 December 2008. Retrieved 24 August 2019.
  22. ↑ Bernardes de Jesus, Bruno; Vera, Elsa; Schneeberger, Kerstin; Tejera, Agueda M.; Ayuso, Eduard; Bosch, Fatima; Blasco, Maria A. (15 May 2012). "Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer". EMBO Molecular Medicine . 4 (8): 691–704. doi:10.1002/emmm.201200245. PMC   3494070 . PMID   22585399.
  23. ↑ Muñoz-Lorente, Miguel A.; Cano-Martin, Alba C.; Blasco, Maria A. (2019-10-17). "Mice with hyper-long telomeres show less metabolic aging and longer lifespans". Nature Communications . 10 (1): 4723. Bibcode:2019NatCo..10.4723M. doi: 10.1038/s41467-019-12664-x . PMC   6797762 . PMID   31624261.
  24. ↑ "Hyper-Long Telomeres Give Non-Genetically Modified Mice Longer, Healthier Lives". Genetic Engineering and Biotechnology News. 2019-10-18.
  25. ↑ Kerry Grens (25 April 2016). "First Data from Anti-Aging Gene Therapy". The Scientist .
  26. ↑ "Telomere Dynamics with Age are Very Different Between Mammalian Species". Fight Aging!. 2019-07-11. It is well known that mouse telomere dynamics and telomerase expression are quite different from that of humans. This might make us suspect that positive results from telomerase gene therapies in mice, where life span is extended and health improved, without raising the risk of cancer, may not hold up in humans. There is no particular reason why increased cancer risk through putting damaged cells back to work will be balanced in the same way by improved tissue function and improved immune function, from species to species. The research and development community will find out in the years ahead by trying telomerase gene therapies in primates and then humans.
  27. ↑ "Home".
  28. ↑ Mitchell, Erick (2024-01-11). "BioViva Aims to Improve Human Longevity". Healthnews. Retrieved 2024-09-09.
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