Category Archives: Immortality Medicine

PUBLIC RELEASE DATE:

25-Apr-2014

Contact: Mark Derewicz mark.derewicz@unch.unc.edu 919-923-0959 University of North Carolina Health Care

April 24, 2014

CHAPEL HILL, N.C. The evidence for what causes aging has typically been limited to the study of a single organism's lifespan; our cells divide many times throughout our lives and eventually cause organs and our bodies to age and break down. But new research from the UNC School of Medicine suggests that how we age might depend on cellular interactions that we inherit from ancestors throughout many generations.

By studying the reproductive cells of nematodes tiny worms found in soil and compost bins Shawn Ahmed, PhD, an associate professor of genetics, identified the Piwi/piRNA genome silencing pathway, the loss of which results in infertility after many generations. He also found a signaling pathway a series of molecular interactions inside cells that he could tweak to overcome infertility while also causing the worms to live longer adult lives.

The research, in collaboration with researchers at the University of Cambridge and described in a paper published in the journal Cell Reports, suggests that it's possible to manipulate the aging process of progeny before they're even born.

The finding gives scientists a deeper understanding of what may govern aging and age-related diseases, such as some cancers and neurodegenerative conditions.

Typically, nematodes produce about 30 generations in a matter of months and remain fertile indefinitely. Ahmed and colleagues found that a mutation in the Piwi/piRNA cellular pathway of germ cells gradually decreased the worms' ability to reproduce as the mutation was passed down through the generations and eventually caused complete sterility. But when Ahmed's team manipulated a different protein DAF-16/FOXO the nematodes overcame the loss of the Piwi pathway. The worms did not become sterile; generations of worms reproduced indefinitely, achieving a sort of generational immortality. Moreover, it has been well established that DAF-16/FOXO plays a role in nematodes living longer.

Achieving longer life suggests that there's an effect on the aging of somatic cells the cells that make up the body and organs of an organism.

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UNC researchers link aging to cellular interactions that occur across generations

PUBLIC RELEASE DATE:

16-Apr-2014

Contact: Sarah Cavanaugh scavanaugh@celldex.com 508-864-8337 Celldex Therapeutics

HAMPTON, NJ (April 16, 2014): Celldex Therapeutics, Inc. (NASDAQ: CLDX) announced today that final data from its Phase 1 study of CDX-1401 in solid tumors, including long-term patient follow-up, have been published in Science Translational Medicine (Vol 6 Issue 232). The data demonstrate robust antibody and T cell responses and evidence of clinical benefit in patients with very advanced cancers and suggest that CDX-1401 may predispose patients to better outcomes on subsequent therapy with checkpoint inhibitors. CDX-1401 is an off-the-shelf vaccine consisting of a fully human monoclonal antibody with specificity for the dendritic cell receptor DEC-205 linked to the NY-ESO-1 tumor antigen. The vaccine is designed to activate the patient's immune system against cancers that express the tumor marker NY-ESO-1. While the function of NY-ESO-1 continues to be explored, references in the literature suggest that its expression might reflect the acquisition of properties that cancers find useful, such as immortality, self-renewal, migratory ability and the capacity to invade.

The Phase 1 study of CDX-1401 is the first clinical study to demonstrate that an off-the-shelf vaccine that targets dendritic cells in vivo through DEC-205 can safely lead to robust humoral and cellular immunityovercoming a significant challenge in the development of protein based vaccines. Targeting protein antigens to the DEC-205 receptor on dendritic cells was pioneered by the late Ralph Steinman, MD, a member of Celldex's Scientific Advisory Board. Dr. Steinman received the 2011 Nobel Prize in Physiology or Medicine for his discovery of the dendritic cell and its role in adaptive immunity. This now-proven ability to target proteins, like NY-ESO-1, to dendritic cells to generate potent immune responses specific to these proteins represents a promising approach for the next generation of vaccines against pathogens and cancer.

"CDX-1401 offers a novel, well-tolerated and practical approach to generating protein specific immunity that can be readily combined with other treatment strategies to boost immunity against pathogens and tumors," said Dr. Madhav Dhodapkar, MBBS, Arthur H. and Isabel Bunker Professor of Medicine and Immunobiology, Chief of the Section of Hematology at the Department of Internal Medicine and Clinical Research Program Leader of the Hematology Program at Yale Cancer Center and lead author of the paper. "The preliminary findings in patients who received therapy with a checkpoint inhibitor following the vaccine provide further rationale for combination immunotherapy strategies, meriting further investigation."

Thomas Davis, MD, Senior Vice President and Chief Medical Officer of Celldex Therapeutics added, "CDX-1401 has overcome a significant historical challenge in the development of protein based vaccines by successfully targeting dendritic cells in vivo. It now sits at the forefront of a new generation of off-the-shelf dendritic cell targeted vaccines that we believe hold significant promise. Based on the results observed in this Phase 1 study, we expect CDX-1401 to enter at least two combination studies this year with both our own investigational therapies and external therapies in melanoma and other indications where we believe a dendritic cell vaccine regimen could play an important role." Initial results from the Phase 1 study of CDX-1401 were presented at the 2012 Society for Immunotherapy Annual Meeting. The manuscript published today expands upon this data and includes longer-term patient follow up.

CDX-1401 Phase 1 Study Overview and Results

The study was designed to assess the safety, immunogenicity and clinical activity of escalating doses of CDX-1401 with TLR agonists (resiquimod and/or Poly ICLC (HiltonolTM) in 45 patients with advanced malignancies refractory to all available therapies. CDX-1401 was well tolerated, with no dose limiting or grade 3 toxicities reported. The most frequently reported adverse events were administration site reaction, fatigue, nausea and chills. Treatment induced humoral and cellular immunity to NY-ESO-1 in patients with NY-ESO-1 expressing tumors across various dose levels and adjuvant combinations.

Significant anti-NY-ESO-1 titers occurred in 79% (33/42) of evaluable patients, with high titers (>1:10,000) in 52% and very high titers (>1:100,000) in 33% of patients. Similarly strong humoral immunity developed in each cohort and in patients with or without confirmed NY-ESO-1 expression in their tumor. Approximately 54% of patients with NY-ESO-1 positive tumors had anti-NY-ESO-1 titers at baseline and most increased after vaccination. NY-ESO-1-specific T cell responses were absent or low at baseline, but increased post-vaccination in 56% of evaluable patients, including both CD4 and/or CD8 T cell responses. Durability of the T cell response was demonstrated in two patients from whom samples from additional cycles of CDX-1401 treatment were available. In these patients, the induction of NY-ESO-1 specific T cells was maintained through three cycles (approximately seven months) of treatment.

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Celldex's Phase 1 study of CDX-1401 published in Science Translational Medicine

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After decades of work, a team of doctors say they've successfully engineered vaginas that have been implanted and grown in women. The vaginas were grown in a lab from the female patients' own cells and later transferred to their bodies, where they formed into normal vaginas. The breakthrough bears some huge implications, too.

It sounds confusing at first, but the process was fairly simple. Anthony Atala from the Wake Forest School of Medicine led the research using a technique developed in the 1990s. The patients were all women born without functioning vaginas due to a rare but severe condition known as Mayer-Rokitansky-Kster-Hauser Syndrome. While they all had vulvas, the external part of the female sex organs, they didn't have a vaginal cavity, meaning they couldn't menstruate or have sex. There were also, obviously, psychological effects.

Using a technique first developed on rabbitswhere, funnily enough, the first solid organ grown was a penisAtala's team took samples from the women's vulvas and grew them on a degradable scaffold made of collagen in a lab. Once they'd reached the right level of maturity, the doctors inserted the engineered vagina into a cavity they'd formed in the patients' abdomens. The scaffold was attached to the uterus and a stent was used to hold it in place for the first six weeks. After just six months, the vagina was fully developed. Depending on the patient, Atala waited between four and eight years before publishing his findings to ensure there were no complications. There weren't.

"After the operation they were able to function normally. They had normal levels of desire, arousal, satisfaction and orgasm," Atala told the press. When asked whether the women could give birth, he sounded optimistic. "They haven't tried," he said, "but they can ovulate, so there is no reason to suspect that they cannot."

While this specific procedure stands to improve the lives of many women, the implications of growing an organ inside a patients' body is huge. Gizmodo interviewed Atala a few years ago, and he spoke of a future where all body parts could be grown in a lab and transplanted into a patient. It makes you wonder, if this is what immortality looks like. "I don't know how long it will take, but I do foresee a future when organs will be available off-the-shelf, ready to 'plug in' and replace injured or diseased organs," Atala said at the time. With today's news, we're that much closer to this future. [The Lancet via New Scientist]

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Doctors Can Now Grow Engineered Vaginas in Women

MIAMI They come to put their dead relatives and friends on a T-shirt.

A young woman clutches a photo of her murdered 16-year-old brother. He grins at the camera, his right hand clutching a gun. Three young men line up to pay homage to one of their friends, a "street soldier," with his Facebook profile picture.

Here at Studio X, inside the U.S.A. Flea Market, miles away from South Beach in a gritty pocket of Liberty City, is where black Miami's killed are memorialized. Pictures of the deceased are stamped onto plaques and necklace charms, but a majority of customers come to put a picture on a T-shirt.

For the bereaved who robe themselves in these memorial shirts, the act is a public expression of their loss. It is a ritual they turn to in their time of grief. It is a testimony of a life prematurely taken by violence in neighborhoods where these killings don't always make the news cycle.

The Studio X booth, with its purpose emblazoned on a sign out front - "Home of the R.I.P. T-shirts" - is often the first stop before funeral arrangements. And long after the funeral is over, the grief-stricken return. They come on their lost loved one's birthday and on the anniversary of the killing for more T-shirts to proclaim their sadness. Here, love is a memorial worn close to the heart and out in the street.

Ayleen Lopez, the soft-spoken graphic designer on duty, gently directs customers to a menu of images beneath plexiglass to use as a background for the photo of their loved ones.

"People do it because it's their way of remembering someone they loved," she said. "Not everyone understands it. In Miami, in the 'hood, this is how you show this person means something to me."

Menu item CR-14 depicts a cross topped with a crown of thorns. CR-17 is a pair of hands clasped in prayer. G-13 is Miami's skyline bordered by what looks like two AK-47 assault rifles on top and, along the bottom, a row of bullets.

Studio X is one of the better-known memorial shirt-printing enterprises locally, but similar businesses dot strip malls and flea markets throughout South Florida. They are part of the urban background of inner cities across the country.

"It should be once in a blue moon, but every week it's another body," said Leonard Brown, who designed memorial shirts for 12 years at StudioX.

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Grief-stricken memorialize loved ones on 'R.I.P. T-shirts'

In a landmark study sure to provoke interest, researchers from the University of Edinburgh have regenerated an aged organ in vivo, inside a living animal to its youthful state though noninvasive manipulation of genes. Its a breakthrough that not only brings hope for a wide variety of age-related ailments, but which fundamentally challenges our idea of what aging is. This study treats the natural impacts of of time like symptoms of a disease and by treating those symptoms it seems to have tracked the cells back to their pre-disease (youthful) state.

The organ in question is the thymus, a small immune node that sits near the heart. It produces T-cells, one of the bodys most important immune response units, but over the course of a lifetime the thymus shrinks and T-cell production slows. This is thought to be one big reason (one of many) that elderly people suffer decreased immune response relative to younger people. This study used1- and 2-year old mice, and saw the typical drop in both thymus size and T-cell production with age.

The thymus is one of the most important parts of the immune system, especially in younger people.

Prior research had already identified a protein called FOXN1 as likely linked to thymus degeneration; its expression levels in the thymus seem linked to that organs fate. The mice in this study were bred with a specific genetic sensitivity, however, so that when exposed to the drug tamoxifen they would begin producing fully youthful levels of FOXN1, regardless of their actual age. It should be pointed out that the fact that these were genetically engineered mice is more crucial to the experimental setup than the therapeutic one; without the need to control for variables, scientists could plausibly increase FOXN1 levels through less convoluted measures.

The results? Mutant mice treated with tamoxifen showed total or near-total regeneration of their youthful thymus, while control mice also given tamoxifen showed predictable thymus function for their age. This held true for both the size of the organ itself and the abundance of the T-cells it produces. The regeneration seems to arise from the fact that FOXN1 is a transcription factor that controls expression of several other genes, and that these genes activate stem cell-like action in some thymus cells. By restoring FOXN1 levels, the researchers seem to have convinced the thymus to de-age itself at least, in this one very specific way.[DOI:10.1242/dev.103614]

The researchers are quick to point out the possible benefits to elderly people, or those afflicted by immune diseases. Increasing the ability to fight infection could also revolutionize hospital medicine, helping vulnerable patients fight infection by overclocking the thymus to produce a boost of white blood cells. Restoring the immune response of sick and elderly people would be, without an ounce of hyperbole, one of the most important medical advances in all of human history.

A separate study found that improper FOXN1 function causes a wasting immune disease. Sad

But this study is a far cry from proof that such utility could actually exist. If nothing else, it stands as an uncomfortable challenge to our ideas about just what agingis. Has the thymus really been regenerated or is it simply bigger and more active than it used to be?We do have a few relatively non-arbitrary measures of cell age, in particular measurements of telomere decay. Telomeres are long stretches of inactive DNA that cap our chromosomes on either end, and which seem to fray and shorten as cells live and replicate. A functional regeneration such as this one, coupled with genetic implants to re-lengthen telomeres and undo other sources of aging damage, could be difficult to distinguish from literal reversal of the aging process. (Read:What is transhumanism, or, what does it mean to be human?)

Thats a long way out, however. In the extreme long term, patchwork replacement of organs and body parts is even prophesied to allow immortality, and this study shows that we might be able to supplement grown organs with regenerated ones. Theres no telling how many tissues might be usefully regenerated with such a simple molecular switch but theres also currently no telling if these regenerated thymuses will continue to function well, or if such manipulation could cause unintended side-effects.

A lot more research is needed before human applications could even be discussed, but its an enticing goal. Any tool that could maintain the bodys own immune system could end up saving both lives and healthcare costs immensely of course, as weve discussed previously though, there could be some massive problems if we all start living to 100 or more.

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Gene therapy successfully regenerates an old organ inside a living animal

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What happens after we die? It's a question that has plagued the human mind since we first developed the concept of "death." The search for an answerand, more importantly, a means of circumventing its effectshas encited organized religion and served to shape one of the foundations of human culture.

We've built pyramids to house our dead in the afterlife, constructed terracotta armies to protect them, sacrificed the living in their honor, and even developed preservation techniques to ward off decompositionall in the effort to somehow defy the permanence of death and resurrect at least a part, however intangible, of the deceased person. Ignoring the mysticism and religious fervor of these practices, they represent little more than elaborate burial techniques, which stubbornly remain a part of modern society.

But unlike the miraculous rebirth of one's soul at the hands of Osiris, the practice of cryonics promises the rebirth of a younger, fitter, and not-dead youall through the miracle of future scientific progress.

Cryonics is the practice of preserving "legally dead" human bodies in extremely cold temperatures with hopes that future advances in medical science can revive their corpses and cure what ails themor, at least, extract their memories and consciousness.

The basic idea is that by rapidly cooling the body after the heart has stopped, but before the brain begins to die from hypoxia, the body is rapidly cooled to extinguish the metabolism and halt decomposition. However, unlike short-term suspended animation techniques that are currently being developed to aid in cardiac and neural surgery, traumatic injury, and similar life-threatening emergencies, cryonics freezes you for the long haul.

Not unlike Miracle Max's distinction between the stages of death in The Princess Bride, there is a very fine but very important distinction between "legally dead" and "brain dead" as it relates to cryonics. Cryonics cannot be performed on someone who is still aliveregardless of how ill, the cryonic process would kill them and that constitutes murder. Cryonic preservation practitioners therefore rely on the information-theoretic definition of death rather than the standard, legal definition.

The subject must be deemed "legally dead" by a medical professional, which denotes when the person's heart has stopped beating. Between the time that the heart stops and the brain suffers irreparable damage from oxygen starvation is when the cryonic preservation process must take place, so that the cellular brain function may someday be restarted.

There are a number of facilities in the United States that handle cryonic preservation, including the Cryonics Institute in Detroit, the American Cryogenics Society in Sunnyvale, California, and the Alcor Life Extension Foundation in Scottsdale, Arizona. Each charges a hefty annual membership fee as well as upwards of six figures to actually preserve your corpse, though you can save a significant sum by preserving only your head or just the brain itself.

Once you're declared legally dead, an emergency response team from one of these facilities first will stabilize the oxygen levels in your blood to maintain minimal brain function during your transport to the cryo facility, as well as pack your body in ice and administer the anticoagulant heparin into your bloodstream to keep your juices flowing.

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Why Freezing Yourself Is a Terrible Way to Achieve Immortality

Neil deGrasse Tyson is a rock star.

Or, maybe it's better to compare the country's most famous astrophysicist to a sports star, the kind who'll spend two hours after every game autographing anything thrust in his direction.

If you have anything more than a passing familiarity with the mass media, you will have noticed that, in the past couple of weeks, this cat has been everywhere: CNN, Colbert, NPR, The New Yorker, Reddit, Good Morning Bakersfield.

I called him up last week and asked if he could come over and tell me about dark energy while I was eating breakfast. I woke up to find him cooking scrambled eggs in my kitchen.

Not that Tyson "NdT" to his friends is doing all this media slogging just for giggles. He's the host of the new Fox iteration of the old show "Cosmos," and he's doing his rounds. By taking on "Cosmos" to explain, educate and entertain audiences with astrophysics, Tyson is making explicit what has been implicit for years: That he is the heir to the late Carl Sagan as America's most famous science "popularizer."

Yes, it's an odd term, awkward, a bit condescending. But it's an indication of how rarely scientists and mainstream audiences actually talk to each other that we haven't come up with a better term for what Tyson does.

So, why is Tyson reviving a documentary show from the 1980s? To me, that's not a very interesting question. The better question is: Why aren't there more like him?

We live in a culture that produces battalions of celebrities, platoons of movie stars, brigades of reality-TV narcissists, posturing hip-hoppers, barely dressed divas, snarky comics, political big-mouths and cable talking heads. That's what we do in America create and maintain fame.

Yet, when it comes to science the very stuff of human intellectual development and exploration Tyson stands pretty much alone on the mountain of celebrity.

How many famous scientists can you name other than Tyson and Sagan?

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Wallace Baine, Baine Street: Why the silence on science?

The Fifth Beatle: The Brian Epstein Story, a meticulously researched, masterfully written and gorgeously illustrated graphic novel by award-winning Broadway producer Vivek J. Tiwary and artist Andrew C. Robinson, was a labor of love. (Cover art by Andrew C. Robinson)

Somewhere, along the mad and transcendental road of rock and roll, the tale of one of its greatest architects, masters and casualties has been lost. Somewhere, between the gyrating hips and rebel snarl of Elvis and the shallow, uninspired gushiness of emo, music history has forgotten one of its first antiheroes. Somewhere, somehow, the man responsible for turning popular culture, music and several generations, worldwide, upside-downand influencing every band sincehas been left for dead and buried, destined for obscurity but for a growing legion of fans-turned-archeologists.

The Fifth Beatle: The Brian Epstein Story, by award-winning Broadway theater producer Vivek J. Tiwary (A Raisin in the Sun, American Idiot, The Addams Family) and artist Andrew C. Robinson, resurrects the seminal Beatles manager, breathing life, color, validity, and resounding beauty, into his short, intense, often-overlooked life and his contributions shaping and molding the four young lads from Liverpool. The Beatles immortality, as documented in this meticulously researched, masterfully written and gorgeously illustrated graphic novel, is Epsteins legacy, as are the boundless torrents of love, hope and optimism shared through their songs.

It was Epstein who shed their leather jackets for matching tailored suits. It was Epstein who got them a record contract. Epstein who landed them in America and on The Ed Sullivan Show. Epstein who invented their synchronized bow, comforted and cared for them, transported them from The Cavern Clubs basement to the center of the worlds stage.

Through The Fifth Beatle, we hear his thoughts, see his struggles, feel his jubilation and his painJewish and gay, yearning for acceptance and self-worth. Visionary, businessman, family man, son, friend, tortured soul, matadorwe see Epsteins genius, his passion, his struggles and his flaws.

This must-read work of arta labor of love for Tiwary, which took 20 years to realizeis a worthy tribute, historical account, comic, biography, love letter and song to a man who shaped and molded music, and life itself.

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REVIEW The Fifth Beatle: The Brian Epstein Story, By Vivek J. Tiwary And Brian C. Robinson

Community HealthNet Health Centers is committed to offering comprehensive healthcare to adults and children. CHN provides a range of acute, chronic and preventative care. In addition to traditional prenatal, pediatric and family medicine services, CHN offers routine check-ups, health and wellness assessments, immunizations, screenings and referral based personalized counseling to individuals of all ages. As a federally qualified health center it is their mission to provide quality and affordable medical services to all individuals in need of health care. CHN has five locations throughout Lake County: Gary (2), Merrillville, Hammond and the school-based clinic in Calumet High School. They employ a staff of licensed and professional physicians who are committed to the health and well-being of their patients.

Since opening its doors in 1998, CHN continues to expand the scope of services that we offer our patients. Partnering with state and local organizations CHN is able to offer more affordable access to preventative health services such as mammograms. These services are made possible through a partnership with the Indiana State Department of Health Breast Cervical Cancer Program (BCCP). Recently CHN opened doors to the first Centering Pregnancy Clinic in Lake County offering a program aimed to improve birth immortality rates and coach mothers through a successful pregnancy. Funded by the March of Dimes, the Centering Pregnancy Clinic is operated by an on-staff certified nurse mid-wife. Just recently CHN partnered with Geminus Corporation to conduct on-site Domestic Violence Prevention trainings helping its medical staff to identify child abuse.

In need of insurance? CHN's got you covered! How about dental services? CHN can brighten your smile. Community HealthNet is partnered with Covering Kids and Families Indiana, a grassroots statewide initiative aimed to enroll individuals, primarily youth in state provided medical plans. As a certified application and enrollment site CHN employs outreach specialists working to educate, enroll and meet the demands of the Affordable Care Act through Marketplace enrollments. At the main site in Gary, CHN is partnered with Kool Smiles to provide dental services to both youth and adults.

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Community HealthNet offers comprehensive healthcare for all

Purpose

To explore the issue of ethics in medical research and, in particular, the issue of informed consent, in the context of Henrietta Lacks and the HeLa cells.

This lesson uses the book, The Immortal Life of Henrietta Lacks, written by Rebecca Skloot, which is one of the winners of the 2011 SB&F Prize for Excellence in Science Books. SB&F, Science Books & Films, is a project of the American Association for the Advancement of Science.

The ubiquitous cell line HeLa (whose immortality provides the book title) has helped power the explosive growth of cell biology for more than 50 years. But for all that is known about the cells themselves, most people know little if anything about the history and the woman behind these cells. In her book, investigative reporter Skloot explores the mystery behind HeLa cells (pronounced hee la), her obsession with telling the real truth about Henrietta Lacks, and the scientists, doctors, and institutions involved in this fascinating story that revolves around Lacks cervical cancer cells.

Its a story the students wont soon forget, which is exactly what happened to Rebecca Skloot. She first heard about HeLa cells at age 16 while attending a community college biology class. Her professor told the class that HeLa cells were the most famous cells ever, and that they came from an African American woman who died of cervical cancer. That was all he knew, and Skloot immediately wanted to know who the donor was, where she came from, if her family knew her cells were still alive, and what her real name was. (Until Skloots book, Lacks was pretty much anonymous.)

Years went by before Skloot had the resources to pursue this mystery, but once she started uncovering the story, she didnt give up, and a decade of research resulted in this award-winning book.

In this lesson, students will read The Immortal Life of Henrietta Lacks and learn what bioethics is and how it has influenced cellular research from the 1950s until now. They will learn what informed consent is and its importance to researchers and patients. They will learn how a major piece of science history has impacted their lives on an individual level. And although they may have heard about the Tuskegee Syphilis Study (which took place at the same time and institution as Lacks story), they also will gain a better understanding of the history behind that medical experiment and its influence on current ethics.

Students should begin this lesson with a basic knowledge about what cells are and how they function. If you feel that your students need to review this knowledge, askthem to answer the questions on the Explaining DNA student sheet in the Extracting DNA science lesson. This student sheet also asks students to create a poster explaining DNA to someone unfamiliar with it.

Ideas in this lesson are also related to concepts found in these Common Core State Standards:

Using the HeLa student esheet, students should begin this lesson by reading Henrietta Lacks' Immortal Cells, which is an interview with the author that summarizes the book and the story behind HeLa cells.

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The Immortal Life of Henrietta Lacks - Science NetLinks