Is experimental gene therapy a bright prospect or something ?

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Is experimental gene therapy a bright prospect or something ? Gene therapies that lack preliminary data and have unproven effects directly find people to try and collect data directly from people.

In order to evade FDA supervision, these experimental treatments are carried out overseas. Those patients who have spent huge sums of money in pursuit of health and longevity do not know what risks they are taking.

More than a month ago, at an academic web conference organized by the National University of Singapore, Elizabeth Parrish, CEO of the American biotech company BioViva, revealed that she was anxiously waiting for an event with 6 volunteers. The result of gene therapy.

This is a study to treat dementia (mostly Alzheimer’s disease) caused by aging. According to the media STAT, last year, 6 patients with dementia went to Mexico to receive anti-aging gene therapy. The identity of the patient cannot be checked, but the invitation letter issued by BioViva in 2019 can be found to recruit 10 patients with mild to moderate Alzheimer’s disease to Mexico City to receive a “one injection” gene therapy study. In the NUS web conference, Parrish stated that he hopes that gene therapy can reverse human aging.

Elizabeth Parrish, CEO of BioViva

BioViva’s director of strategic planning, Dave Kekich, confirmed to STAT that six people have been treated, and said that these people must prove that they have dementia symptoms in order to participate in the treatment trial. Kekich said: “This is an overseas medical tourism business aimed at testing experimental therapies.”

If all this is true, this will be the world’s first public clinical study on the treatment of Alzheimer’s disease with gene therapy. Although the efficacy of anti-aging gene therapy has not been proven, there are still many desperate people who want to extend their lifespan to receive the injection through cross-border travel, which will change the genes in the body forever.

Is aging a disease?

Since ancient times, birth, old age, sickness and death has been an inescapable destiny for every human individual, and “immortality” is also a dream that mankind has never given up.

In the late 1970s, three scientists, Elizabeth Blackburn, Carol Greider, and Jack Szostak, discovered that there is a unique DNA sequence in the telomere at the end of the chromosome that protects the chromosome from degeneration. And an enzyme called “telomerase” (telomerase) makes telomeres. When the telomerase activity is high and the telomere length is maintained, cell senescence can be delayed. This is the case for cancer cells. These research work won the 2009 Nobel Prize in Physiology or Medicine for the three. At this point, it can be said that mankind has uncovered the mystery of aging.

So, is it possible to artificially control the length of telomeres and delay aging? Everything is far from being as simple as imagined. Telomerase is a double-edged sword: when telomerase is activated, cells can exhibit the ability to proliferate indefinitely, which is the so-called cancer cell. In most cancers, increased telomerase activity can be observed.

So far, the FDA has not defined aging as a disease. Many anti-aging therapies in clinical research are actually aimed at certain specific diseases related to aging.

But Parrish believes that aging itself is a disease-in other words, aging can be treated. Gene therapy can be used to supplement human cells with some genetic code, extend their chromosomes, form stronger muscles, and promote the production of more proteins to resist oxidative stress (one of the causes of aging).

In recent years, transgenic technology (transferring foreign genes into recipient biological cells and expressing them) has been fully developed, and small companies like BioViva may also apply it to anti-aging research. However, Parrish didn’t want to wait. Existing regulations require that a large number of laboratory studies and animal studies must be used to determine whether gene therapy is applicable to humans before costly human trials. This may take more than ten years, or even decades.

Parrish didn’t want to wait for decades. She said in an interview: “The power of genetic technology is already there, but we can’t control it, because no one can raise so much money to use these controversial therapies in clinical trials.” According to her The idea is that the FDA should relax its supervision, and as long as patients are willing to try, it should allow doctors to apply effective therapies in animal models to humans. However, it is impossible for the FDA to do that, so sending the patient overseas for treatment is the best solution-at least it can start the human trial process without stagnation and waiting.

“As long as you have the first person’s data, you can attract investors, and if someone invests in this technology, you can let the world enjoy its benefits.” Parrish practiced her own philosophy-she secretly carried her family behind her back. He received more than 100 injections and received an experimental gene therapy.

Cross-border medical care

The idea of ​​gene therapy was first published in 1972. It refers to the use of harmless viruses to transport normal non-mutated genes to patients with genetic mutations, and normal gene expression replaces diseased genes with genetic mutations. After decades of development, twists and turns, and several trials that led to the death of human subjects, the FDA finally approved the first gene therapy drug LUXTURNA in 2017 to treat a rare hereditary blindness. Since then, at least 9 gene therapies have been marketed in the United States for the treatment of certain types of cancer and some inherited orphan diseases.

After the discovery of the function of telomerase, scientists at the Bay Area biotechnology company Geron Corporation mapped out the genetic map of human telomerase in the early 1990s. The leader of this team is called Bill Andrews. A few years later, he designed a virus that can express telomerase in the human body. These viruses are the viral vectors injected into Parrish’s body.

“I didn’t know she was going to call myself.” Andrews said in an interview with SATA. However, after Parrish was injected with a viral vector designed by Andrews in 2015, the two immediately began planning to open an overseas gene therapy clinic under the BioViva name. By 2017, the two’s plan gradually died, and Andrews transferred his technology to another company, Libella Gene Therapeutics.

At first, Libella tried to recruit patients to participate in its paid trial of telomerase gene therapy. The company said the trial will be conducted in India to treat the middle and late stages of Alzheimer’s disease. In an interview in 2019, Libella CEO Jeff Mathis told STAT reporters that the expected treatment cost for the first patient is US$11 million.

But this experiment seems to have failed in the end. Libella instead tried to carry out a small-scale telomere repair trial in Colombia, and each patient charged $1 million for gene therapy. In a 2019 interview with MIT Technology Review, company executives stated that they had recruited two patients; but in the latest STAT interview, Andrews stated that no one had received this treatment.

During this period, BioViva’s business turned to bioinformatics, analyzing test data for companies that sponsored the research. Its biggest partner is Integrated Health Systems (IHS). IHS is an intermediary system that refers patients to doctors who practice medicine outside the United States who are willing to provide unproven experimental treatments. On social media, IHS claims to have “a group of gene therapy experts.” On the official website of IHS, there is only one doctor-a radiologist named Jason R. Williams, who is also the chief medical officer of BioViva and also runs a “Williams Cancer Institute” (Williams Cancer Institute) in Mexico City. Institute), opened cancer immunotherapy business.

Williams Cancer Institute. The six-person IHS trial is conducted here

Williams has a long history of using experimental therapies. In 2012, he founded a company called Precision StemCell to provide unproven stem cell therapies to desperate patients, covering spinal cord injury, progressive freezing (ALS), and even children with hereditary blindness. In the same year, Leigh Turner, a bioethicist at the University of Minnesota, wrote to the FDA asking the FDA to intervene in the matter. Later, Williams said in an interview that the FDA required him to stop treatment and must obtain regulatory approval, so he stopped the experimental stem cell therapy in 2013.

After that, Williams transferred to Bogotá, the capital of Colombia, to open a clinic, and founded a company called Neuralgene, claiming to be testing a gene therapy for frostbite. According to the company’s official website, Williams subsequently moved the company to Mexico as CEO and R&D director. The website did not list any other employees.

In July 2019, BioViva posted a video on YouTube announcing that IHS is launching a telomerase gene therapy study, looking for patients with mild to moderate Alzheimer’s disease to participate in treatment, and published the Facebook homepage of the IHS plan. In August, BioViva sent an email promoting this research to its followers, stating that the company will treat patients for free, and that the $62,000 treatment fee will be funded by a non-profit organization that specializes in sponsoring anti-aging research—— The Maximum Life Foundation Foundation undertakes.

Coincidentally, the president and CEO of the Maximum Life Foundation is Dave Kekich, the strategic planning director of BioViva mentioned above.

The HIS Questions and Answers (FAQ) and signature form provide detailed information about the HIS program: The research will be conducted at the Williams Cancer Institute in Mexico City; participants will pay for their travel expenses; they will receive telomerase once upon arrival Gene therapy to “rejuvenate” the microglia in the brain. The entire treatment process is about one hour, but it is recommended that the patient stay for 4 to 5 days to prevent adverse reactions. These documents indicate that the HIS program selected participants as early as the spring of 2019, and planned to arrange treatment between April and October of that year.

According to the description of the IHS project, the participants in the study are all healthy people over 50 years of age who may be diagnosed with Alzheimer’s disease and accompanied by a reliable caregiver. HIS requires applicants to participate in the entire research process to ensure that the research results can be extended to a wider range of people. The answer reads: “It is an honor to apply for and participate in this research.”

HIS official website homepage

STAT media submitted all the materials it found about the IHS program to Leigh Turner, a bioethicist at the University of Minnesota, for review. Turner studies the medical tourism industry. He said that the language used in these materials touted potentially effective treatments would mislead and manipulate participants. According to clinical research specifications, researchers must disclose the approved research design and methods to the public in databases such as Clinicaltrials.gov before recruiting participants. The disclosure checklist should describe what kind of drugs the patient will receive, the dose to be administered, the frequency of administration, the location of the study, the way the study is administered, the criteria for measuring the effect of the treatment, and when the study is terminated if the trial starts to fail.

All of this, IHS material almost didn’t mention a word.

Turner said: “Everything I have seen shows that the clinical trials conducted in this study are unpredictable and unreliable.”

Liz Parrish and Bill Andrews talk and discuss in the video

Parrish and Williams have known each other for a long time, although they rarely meet. The two appeared together in multiple videos on BioViva’s YouTube channel, talking about different genetic methods of anti-aging. In these conversations, Parrish will refer to the collaborative research between his company and Rutgers University from time to time. In other videos, she also mentioned George Church of Harvard University.

The big guy who surfaced

In 2018, BioViva began funding Rutgers University microbiologist Hua Zhu’s research on the herpes virus. Help work. In the past few years, the Zhu Hua team has been using mice as experimental animals to test a recombinant cytomegalovirus (recombinant cytomegalovirus) to see if it can replace the commonly used adeno-associated virus (AAV) as a gene therapy vector . Zhu Hua introduced to the STAT reporter an unpublished work in the laboratory: they infected mice with recombinant cytomegalovirus loaded with some anti-aging genes (including telomerase). The results showed that compared with mice in the control group The life span of mice injected with recombinant cytomegalovirus carrying anti-aging genes was extended by about 40%, and the effect was “very significant.”

Left: Zhu Hua; Right: George Church

George Church, Robert Winthrop Professor of Genetics at Harvard University, has been involved in mouse research in Zhu Hua’s laboratory. In the lab’s upcoming papers, Church is the co-author. At the same time, as a world-renowned genetic engineer, Church has been serving as the scientific consultant of BioVova so far.  He said that he knew that BioViva had been interested in clinical trials of telomerase gene therapy, but he did not know that the company’s partners were paying for the trial therapy in Mexico.

In 2015, Church Laboratories accepted and analyzed part of Parrish’s blood samples collected by Williams in the Bogotá trial. STAT asked if he had received samples and data from Alzheimer’s patients in the IHS program, which Church denied.

Bioethicist Turner worries that celebrity scientists like Church are providing credibility for an action that may endanger people-human clinical trials that are out of supervision will bring great risks to subjects. Turner believes: “The activities of these companies are disturbing in many ways. You don’t want scholars from well-known research institutions to provide them with protective functions.” “So, if he (George Church) intends to make such Companies that borrow their names are responsible for preventing them from doing wrong things.”

In response, Church responded: “A little help to Rutgers University’s (unusual) mouse experiment, is it even if it provides a protective function?” “In the past, I emphasized the need to support some appropriate clinical trials. I still emphasize that.”

A few days ago, after the six-person IHS trial in Mexico was made public by STAT, Church contacted Parrish. He told STAT: “I think the media’s comments are reasonable, so I have contacted Liz, hoping to further clarify and change certain aspects.”

Who provided the test materials to IHS?

Strangely, until now, no one knows where the IHS program is to obtain the viral vectors needed for treatment. Zhu Hua said that his laboratory only makes mice, and he has never participated in the research of viral vectors for humans. Parrish also said that BioVivo did not provide test materials: “We do not have the ability to create vectors.” She said that her team’s role is to analyze the treatment data of six patients.

California biotechnology company Virovek supplies the adeno-associated virus vector (AAV) required by most scientific research institutions in the United States. Is it possible? STAT went to ask if it provided materials for any of the IHS or Williams trials, and Virovek did not respond.

Generally, the FDA also has high requirements for the vectors used in gene therapy. The production process of the vector is an important part of a successful gene therapy. The purity and integrity of the vector directly affect the effect and toxicity of gene therapy. The biotechnology company Solid Bioscience has a gene therapy for Duchenne muscular dystrophy. The FDA has suspended it for nearly a year due to severe clinical side effects. It was not approved to restart clinical trials until they improved the production process of the viral vector.

Without knowing the source of the viral vector, the safety guarantee for these 6 patients is even more slim.

But the sponsors of the trial didn’t care about this. Most importantly, they will have data soon.

Parrish said her team has been following these patients for 8 months, and she hopes to share the results of these 8 months with the public in early June.

Andrews couldn’t hide the joy in his heart: “I am eager to see the data.” Although he is now a competitor of BioViva, he hopes to see his ideas come true now.

In contrast, Church appears more cautious. He knows very well that “the current telomerase therapy is only effective in animals.” Whether this technology is mature enough to be used in humans is still a very complicated question. The biggest concern in the academic world is that telomerase can transform healthy cells into malignant cells that divide indefinitely, leading to cancer. At the same time, his caution is accompanied by optimism: “I think the problem is still telomerase. I will not hide the problem. I am not sure if it can be used for humans now, but it will be soon. Soon.”

This senior genetic engineer should also be very clear that if the results of animal experiments can be easily repeated in humans, most of the existing diseases would have been overcome long ago. To prove that a drug is safe and effective for humans, it must go through rigorous clinical trials. It is not a matter of just giving a few people a try to draw a conclusion.

(source:internet, reference only)

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