 | This article needs more reliable medical references for verification or relies too heavily on primary sources .(July 2016) |  |
BioViva is an American biotechnology gene therapy company, based in Bainbridge Island, Washington, researching treatments to interfere in the aging process in humans.
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| Founded | 2015 |
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| Headquarters | Bainbridge Island, Washington, |
BioViva was founded in 2015. [1] The CEO, Liz Parrish, started the company by taking gene therapies associated with lengthening lifespans in model organism, [2] 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. Remember, BioViva is not a research organisation. We are taking things like gene therapies and using them like technology." [3] Since then the company has gone into research and development and patented AAV based gene therapies [4] and launched a new gene therapy platform with CMV as the vector. [5] 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. [6]
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. [7] 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." [8] 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. [9] 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. [10]
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." [11] Since BioViva released a peer reviewed paper that showed lengthening of telomeres over years and the press has change in their favor [12]
The Hallmarks of Aging papers seems to have created a platform in with to launch gene therapies that target these hallmarks. [13] [14] 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. [15] 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." [10]
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. [10] Prof Martin has since died of aging associated illness.[ citation needed ] But other advisors for BioViva have stayed, including Prof George Church of Harvard who have continued to advocate for the company and has showed BioViva's most recent data in several virtual talks as of 2024 [16]
Bad press ensued the companies efforts to usher in new treatments as 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." [17] Since then many companies have started on the same pursuit including Jeff Bezos multi billion dollar endeavor called Altos and Google's anti aging company called Calico.
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. [18] 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 showed Using CMV showed an increase in life extension of 42% for a telomerase inducing gene therapy and 32% for a follistatin inducing gene therapy. [19] 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. [20] [21] [22] [23] 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. [24] However, some experts draw attention that the results of studies in mice cannot always be directly transferred to humans. [25]
In 2021. BioViva again came under media interest in there involvement of assessing data of a human investigator lead study for dementia. [26] 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, but BioViva was given the patent for assessing this data. Parrish says the patent is pending. [27]
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 and/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.
Life extension is the concept of extending the human lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled biological limit of around 125 years. Several researchers in the area, along with "life extensionists", "immortalists", or "longevists", postulate that future breakthroughs in tissue rejuvenation, stem cells, regenerative medicine, molecular repair, gene therapy, pharmaceuticals, and organ replacement will eventually enable humans to have indefinite lifespans through complete rejuvenation to a healthy youthful condition (agerasia). The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists.
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.
The Hayflick limit, or Hayflick phenomenon, is the number of times a normal somatic, differentiated human cell population will divide before cell division stops. However, this limit does not apply to stem cells.
Dyskeratosis congenita (DKC), also known as Zinsser-Engman-Cole syndrome, is a rare progressive congenital disorder with a highly variable phenotype. The entity was classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, and MDS/AML, but these components do not always occur. DKC is characterized by short telomeres. Some of the manifestations resemble premature ageing and cognitive impairment can be a feature. The disease initially mainly affects the skin, but a major consequence is progressive bone marrow failure which occurs in over 80%, causing early mortality.
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.
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.
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.
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.
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.
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).
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.
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.
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.
