Mad Scientist Detected! BioViva CEO Uses "Anti Aging" Gene Therapy on Herself

The way BioViva founder Elizabeth Parrish sees it, biological aging is a disease – and she’s willing to bet her life on a cure.

Last fall, the 45-year-old Seattle-area woman underwent an experimental type of gene therapy aimed at addressing some of the big effects of aging, including loss of muscle mass and a shortening of the chromosomes’ telomeres. The procedure was reportedly done in Colombia, to get around U.S. regulations.

The idea of having gene therapy done on yourself raised eyebrows in the biotech community, but Parrish was unfazed.

“I 100 percent believe that it will work, or else I wouldn’t have done it,” Parrish told GeekWire during an interview in February. “I didn’t try to flame out in glory. The research shows that it should absolutely work.”

Now BioViva is reporting that it does seem to work, at least on Parrish’s telomeres. And that’s likely to fuel a debate over the widening scientific quest for greater longevity – conducted not only by BioViva, but by other ventures such as Human Longevity Inc. This week, Human Longevity announced a 10-year deal with AstraZeneca to analyze 500,000 DNA samples for anti-aging clues.

Parrish is already trying to follow up on a couple of clues through Bioviva USA, the privately held company she founded on Bainbridge Island last year. Bioviva announced its own deal this week with a London-based investment fund called Deep Knowledge Life Sciences.

One of BioViva’s anti-aging clues has to do with a protein called myostatin: Research suggests that genetically blocking the production of myostatin could help preserve age-related muscle loss.

The other clue has to do with telomeres, the stretches of DNA at the ends of our chromosomes that are thought to protect our genetic data from harmful mutations – much as the plastic tips on the ends of shoelaces keep them from unraveling. As we age, those telomeres become shorter, and the protective effect is gradually lost.

The gene therapy that Parrish underwent was aimed at inhibiting myostatin and building up telomeres.

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Beyond Extraordinary Claim: Harvard Prof Claims Aging Cure Within 5 Years

At the gene-editing summit, you can’t miss George Church. He’s the big guy with the bushy beard and wavy hair, someone who looks like he stepped out of an 18th century painting of “natural philosophers.” Church, who is 61, is among several hundred scientists, policymakers and thinkers on hand to discuss the powerful technology known as CRISPR, a new method for editing genes. The technique was invented in the past four years, and Church is among those who can claim at least partial credit for the innovation (there’s an intense legal battle over patents — a story for another day).

I mentioned to Church that this is the kind of work for which Nobels are awarded. He quickly responded that there are more important things in the balance than prizes. There are cures for human diseases, he said.

Church thinks that one of the ailments he can cure is aging. When I met him early this year, in his laboratory at Harvard Medical School, where he is professor of genetics, he expressed confidence that in just five or six years he will be able to reverse the aging process in human beings.

“A scenario is, everyone takes gene therapy — not just curing rare diseases like cystic fibrosis, but diseases that everyone has, like aging,” he said.

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1 Year Old Baby's Life Saved by Gene Therapy, may be Cured of Leukemia

For the first time ever, a person’s life has been saved by gene editing.

One-year-old Layla was dying from leukaemia after all conventional treatments failed. “We didn’t want to give up on our daughter, though, so we asked the doctors to try anything,” her mother Lisa said in a statement released by Great Ormond Street Hospital in London, where Layla (pictured above) was treated.

And they did. Layla’s doctors got permission to use an experimental form of gene therapy using genetically engineered immune cells from a donor. Within a month these cells had killed off all the cancerous cells in her bone marrow.

It is too soon to say she is cured, the team stressed at a press conference in London on 5 November. That will only become clear after a year or two. So far, though, she is doing well and there is no sign of the cancer returning. Other patients are already receiving the same treatment.

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Ancestral (but tailored) Adeno-associated Virus Created, may be Useful as Gene Therapy Vector

In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector

Authors:

Zinn et al

Abstract:

Adeno-associated virus (AAV) vectors have emerged as a gene-delivery platform with demonstrated safety and efficacy in a handful of clinical trials for monogenic disorders. However, limitations of the current generation vectors often prevent broader application of AAV gene therapy. Efforts to engineer AAV vectors have been hampered by a limited understanding of the structure-function relationship of the complex multimeric icosahedral architecture of the particle. To develop additional reagents pertinent to further our insight into AAVs, we inferred evolutionary intermediates of the viral capsid using ancestral sequence reconstruction. In-silico-derived sequences were synthesized de novo and characterized for biological properties relevant to clinical applications. This effort led to the generation of nine functional putative ancestral AAVs and the identification of Anc80, the predicted ancestor of the widely studied AAV serotypes 1, 2, 8, and 9, as a highly potent in vivo gene therapy vector for targeting liver, muscle, and retina.

Glybera: The First Gene Therapy "Drug" Released in Europe

The Western world's first gene therapy drug is set to go on sale in Germany with a 1.1 million euro ($1.4 million) price tag, a new record for a medicine to treat a rare disease.

The sky-high cost of Glybera, from Dutch biotech firm UniQure and its unlisted Italian marketing partner Chiesi, shows how single curative therapies to fix faulty genes may upend the conventional pharmaceutical business model.

After a quarter century of experiments and several setbacks, gene therapy is finally throwing a life-line to patients by inserting corrective genes into malfunctioning cells - but paying for it poses a challenge.

The new drug fights an ultra-rare genetic disease called lipoprotein lipase deficiency (LPLD) that clogs the blood with fat. The medicine was approved in Europe two years ago but its launch was delayed to allow for the collection of six-year follow-up data on its benefits.

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New, Promising Gene Therapy for X-linked Severe Combined Immunodeficiency Syndrome

A new form of gene therapy for boys with X-linked severe combined immunodeficiency syndrome (SCID-X1), a life-threatening condition also known as "bubble boy" disease, appears to be both effective and safe, according to a collaborative research team from Dana-Farber/Boston Children's Cancer and Blood Disorders Center and other institutions conducting an international clinical trial. Early data suggest that the therapy may avoid the late-developing leukemia seen in a quarter of SCID-X1 patients in pioneering gene therapy trials in Europe more than a decade ago.

Eight of nine boys recruited to date onto the trial are alive between 12 and 38 months after treatment, with no SCID-X1-associated infections, the research team reported today in the New England Journal of Medicine. Gene therapy alone generated functioning immune systems in seven of the eight. Genetic studies of the boys' new T-cells, which are critical components of the body's immune system, reveal that the viral vector used to deliver the gene therapy did not lead to an expansion of cells with vector insertions near known cancer-causing genes, raising cautious hopes about the vector's long-term safety. One child died of an overwhelming infection present at the time gene therapy began. Left untreated, boys with SCID-X1 usually die of infection before their first birthday.

The investigators will continue to monitor the patients for any signs of treatment-related leukemia for 15 years. In the prior European trials—which were the first to demonstrate gene therapy's potential to successfully cure a disease—leukemia appeared two to five years after treatment. This outcome was one of several events that together slowed clinical progress in gene therapy for many years.

The modified vector created for the current trial is a self-inactivating gammaretrovirus, designed to deliver its payload effectively while minimizing the chance of inadvertently turning on genes, called oncogenes, that could lead to leukemia.

"Our goal was to take the molecular data from the prior trial and use it to produce a vector that would remain effective and at the same time reduce the risk of leukemia," said David A. Williams, MD, a leader of Dana-Farber/Boston Children's, chief of the Division of Hematology/Oncology and director of clinical and translational research at Boston Children's Hospital, principal investigator for the gene therapy trial's U.S. sites, and corresponding senior author of the NEJM paper. "The efficacy data from our study is clear: The vector does work to correct the disease. And by a surrogate endpoint, we have improved the treatment's safety, although it's too early to say that we've completely eliminated the long-term risk of leukemia."

After a single round of treatment, six of the seven boys for whom the gene therapy was successful had achieved the trial's primary efficacy endpoints—a T-cell count greater than 300 cells per microliter of blood and T-cell proliferation in response to stimulation with phytohemagglutinin (a test used to measure T-cells' ability to react to pathogens). The seventh boy received a second round of gene therapy and remains healthy despite having relatively low T-cell counts. The eighth surviving patient was successfully treated with a conventional hematopoietic (blood-forming) stem cell transplant after gene therapy failed to stimulate T-cell production.

"Only a minority of babies with SCID-X1 have the optimal donor for standard transplant, a brother or sister who is tissue-type matched," said co-lead author Sung-Yun Pai, MD, a pediatric hematologist/oncologist at Dana-Farber/Boston Children's. "For the rest, gene therapy is a therapeutic option that avoids the need to find an alternative donor and avoids complications of allogeneic transplant such as graft-versus-host-disease."

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CRISPR: a new Genetic Tool for Gene Repair

Scientists from many areas of biology are flocking to a technique that allows them to work inside cells, making changes in specific genes far faster — and for far less money — than ever before.

"It's really powerful, it's a really exciting development," says of the University of Massachusetts Medical School. He won the in 2006 for that also lets scientists modify how genes work. But, Mello says, this new genetic tool – known as CRISPR for — is more powerful, "because now you can essentially change a genome at will to almost anything you want. The sky's the limit."

Sure, scientists previously have made enormous strides in their ability to do things with genes: modifying them, moving them from cell to cell, even animal to animal.

But doing these things has been time consuming and expensive. It looks like CRISPR will change all that.

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Genetic Modification of Sperm Now Demonstrated, Practical

Get ready: The "new genetics" promises to change faulty genes of future generations by introducing new, functioning genes using "designer sperm." A new research report appearing online in The FASEB Journal, shows that introducing new genetic material via a viral vector into the sperm of mice leads to the presence and activity of those genes in the resulting embryos. This new genetic material is actually inherited, present and functioning through three generations of the mice tested. This discovery—if successful in humans—could lead to a new frontier in genetic medicine in which diseases and disorders are effectively cured, and new human attributes, such as organ regeneration, may be possible.

"Transgenic technology is a most important tool for researching all kinds of disease in humans and animals, and for understanding crucial problems in biology," said Anil Chandrashekran, Ph.D., study author from the Department of Veterinary Clinical Sciences at The Royal Veterinary College in North Mimms, United Kingdom.

To achieve these results, Chandrashekran and colleagues used lentiviruses to generate transgenic animals via the male germ line. When pseudotyped lentiviral vectors encoding green fluorescent protein (GFP) were incubated with mouse spermatozoa, these sperm were highly successful in producing transgenics. Lentivirally-transduced mouse spermatozoa were used in in vitro fertilization studies and when followed by embryo transfer, at least 42 percent of founders were transgenic for GFP. GFP expression was detected in a wide range of murine tissues, including testis and the transgene was stably transmitted to a third generation of transgenic animals.

"Using modified sperm to insert genetic material has the potential to be a major breakthrough not only in future research, but also in human medicine," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "It facilitates the development of transgenic animal models, and may lead to therapeutic benefits for people as well. For years we have chased effective gene therapies and have hit numerous speed bumps and dead ends. If we are able to able to alter sperm to improve the health of future generations, it would completely change our notions of 'preventative medicine.'"

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Gene Therapy For SIV Suggests Route for HIV Immunization

The quest for an HIV vaccine has been given a bad prognosis recently, due to increasing agreement that the human immune system isn't clever enough to outsmart the ever-changing surface of the virus. But now a new approach promises to solve the problem by sidestepping the immune system altogether, instead using gene therapy to produce immune molecules that neutralize the virus.

Reporting in Nature Medicine this week, Philip Johnson, a professor of pediatrics at the University of Pennsylvania, in Philadelphia, and his colleagues managed to protect monkeys from infection with the simian immunodeficiency virus (SIV), the animal model that is closest to HIV, by shuttling a gene into their muscles that produces antibody-like molecules that work against SIV.

[...]

Some antibodies have been shown to neutralize SIV, although exactly how they do this is not well understood. Getting the human immune system produce the few known antibodies that show similar potential for neutralizing HIV has also been impossible.

To tackle this problem, Johnson turned to another virus for help. A modified version of the adeno-associated virus (AAV) has been proved to work as a convenient vector for delivering gene snippets safely into the human body for gene therapy, and it has been used successfully to treat hemophilia and congenital blindness by supplying patients with genes that are otherwise missing.

Johnson and his colleagues designed DNA sequences for particularly stable versions of two antibodies known to be effective against SIV. They used antibody-like molecules, called immunoadhesins, in which the functional part of an antibody is fused with a more stable section of another antibody

The team engineered the immunoadhesin sequences into the AAV vector and injected the constructs into the muscles of nine rhesus macaques, where the muscle cells then started to produce the chimeric antibodies and secrete them into the bloodstream. After four weeks, the team infected the monkeys with SIV and monitored their health along with antibody and virus levels in their blood over one year. Six of the nine macaques showed no sign of SIV infection, and the remaining three did not develop AIDS during the course of the study. In contrast, six control monkeys all became infected, and four of them died before the experiment finished.

The results are "really encouraging," says Andrew Sewell of Cardiff University's School of Medicine in the U.K., who was not involved in the study. "I have not seen anything that worked this well before."

"This has given us a really big green light in the monkey model, but of course we still need to show this also works in humans," says Johnson. There are four potent antibodies that work against HIV, and it may be possible to use the AAV vector to deliver the necessary genetic sequences for the antibodies in humans. Johnson hopes to get permission to start clinical trials soon and is optimistic that the technique can be adapted to humans. If successful, he says, it could turn into an affordable way to protect against HIV.

*crosses fingers*

Tinkered Virus 'Cured' Cystic Fibrosis in Lab

Researchers from the University of California, Berkeley, and the University of Iowa have turned a relatively benign virus into a highly infectious form that is ideal as a carrier for gene therapy.

In its first gene therapy test, it completely cured human cystic fibrosis lung tissue in culture.

This success with the benign adeno-associated virus (AAV), published this week in the online early edition of the journal Proceedings of the National Academy of Sciences, overcomes a major problem of earlier virus-based gene therapy for cystic fibrosis, and sets the stage for tests in advanced animal models of the disease.

"I think it is worthwhile thinking about clinical therapy at the levels of infection we are achieving," said coauthor David Schaffer, professor of chemical engineering at UC Berkeley.

A new pig model of cystic fibrosis developed last year by Schaffer's colleague, pulmonologist Joseph Zabner of the University of Iowa Hospitals and Clinics in Iowa City, will provide a key test of the virus as a carrier of a gene to replace the mutated gene responsible for the disease.

"If we are able to show that efficient gene transfer can result in gene therapy, if we can cure the lung disease of pigs that have been genetically engineered to have cystic fibrosis lung disease, we should have a real chance of curing cystic fibrosis in humans," Zabner said in an e-mail.

Schaffer's lab is collaborating with groups elsewhere to adapt the virus to gene therapy for other diseases, including Alzheimer's disease and amyotrophic lateral sclerosis (Lou Gehrig's disease).

"Both of those are situations where improvements in the properties of the vehicle can have a significant impact on the success of the therapy,"
Schaffer said.

I've always felt that gene therapy was being undersold while stem cells have been waaaaaaaaaaaay oversold. There is SOOOO much potential for, well, cures from lots of nasty diseases that are genetic in nature that stem cells are only patching...at best.

Besides, stem cells can and do cause cancer too. GT also has less squicky bits morally, too, fora lot of people. Oh wait, we're still messing with God's work. Doh.

That's just me. More money for gene therapy!