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Immunology

Working Together To Drug the Undruggable – Technology Networks

PhoreMost, a UK-based biopharmaceutical company dedicated to drugging undruggable disease targets, has announced that it has entered into a multi-project drug discovery collaboration with Boehringer Ingelheim, a pharmaceutical company developing therapies for diseases with unsatisfactory treatments. Under the terms of the agreement, PhoreMost will receive an upfront payment and research funding together with downstream success-based milestones.

PhoreMost will deploy its next-generation phenotypic screening platform, SITESEEKER, towards disease-relevant pathways nominated by Boehringer Ingelheim. Novel targets identified will be further validated and characterized by Boehringer Ingelheim as part of its internal Discovery Research pipeline. Boehringer Ingelheims Research programme is active in the fields of immunology and respiratory diseases, cardiometabolic diseases, oncology research and immuno-oncology, as well as diseases of the central nervous system.

The SITESEEKER platform is based on PhoreMosts core proprietary protein interference, or PROTEINi, technology. Using SITESEEKER, PhoreMost probes the entire proteome in a live cell environment for novel druggable targets linked to any chosen disease, using the vast 3-D shape diversity of natural protein fragment (sub-domain) libraries. This enables the systematic unmasking of cryptic druggable sites, directly linking them to useful therapeutic functions.

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Working Together To Drug the Undruggable - Technology Networks

Immunology

RootPath Raises $11 Million Series A to Accelerate Clinical Translation of its Proprietary Synthetic Immunology Platform – PRNewswire

CAMBRIDGE, Mass., Jan. 6, 2020 /PRNewswire/ --RootPath, a preclinical-stage biotechnology company aiming to enable personalized, highly-potent T cell therapy powered by its proprietary Synthetic Immunology Platform, today announced a $11 million Series A funding round. New investors include Oriza Seed with participation from existing investors Sequoia Capital China, Volcanics Venture, BV (Baidu Ventures) and Nest.Bio Ventures. The company will use the Series A proceeds to validate its tumor-reactive T cell receptor (TCR) discovery workflow, select a lead therapeutic candidate, demonstrate its safety and efficacy in preclinical models and begin IND-enabling development activities.

Launched in 2017 by Nest.Bio Ventures, RootPath has developed a suite of proprietary technologies that comprise its Synthetic Immunology Platform to rapidly and inexpensively recreate T cell immune repertoires and to emulate their antigen-driven selection process in vitro. The Synthetic Immunology Platform centers on the rapid and ultrahigh-throughput generation and functional selection of TCRs, and forms the basis of the personalized T cell therapy that RootPath is advancing. The company had previously announced a $7 M seed round in 2018 led by Sequoia Capital China.

Cell therapies such as chimeric antigen receptor (CAR) therapies have delivered notable successes in hematological malignancies. "The hurdle to achieving effective cell therapies for solid tumors has been identifying safe and effective tumor-reactive agents for these T cells, either as CAR or TCR," said Xi Chen, Ph.D., co-founder and CEO. "Because of the way T cells recognize tumors, discovering tumor-reactive agents for each individual patient or each sub-population of patients has been economically infeasible using existing technologies. This is why we spent the past two years developing our proprietary Synthetic Immunology Platform, which takes advantage of many breakthroughs in synthetic biology and overcomes many intrinsic challenges in immunology-oriented research and drug discovery."

"We are excited to have the support from our new and existing investors to move from technology development to therapeutic translation of our platform," Chen continued.

"Solid tumors are substantially more challenging than hematological malignancies, but, at the same time, represent a more attractive and valuable market," said Grace Yang, Partner of Oriza Seed. "The unique approach RootPath takes effectively creates T cells armed with more targeted weapons, which should translate to increased efficacy and reduced toxicity to patients. We are confident in the Synthetic Immunology Platform, and look forward its clinical translation as well as synergy with potential product candidates from other companies in our existing immuno-oncology portfolio."

About RootPathRootPath is a preclinical-stage biotechnology company pioneering personalized immunotherapy and cell therapy for solid tumors using its proprietary Synthetic Immunology Platform. RootPath was launched by Nest.Bio Ventures in 2017 and has raised $18M in seed and Series A financing. RootPath is located in Cambridge, MA with additional research activities at two sites in China.

SOURCE RootPath

https://www.rootpath.com

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RootPath Raises $11 Million Series A to Accelerate Clinical Translation of its Proprietary Synthetic Immunology Platform - PRNewswire

Immunology

Molecular mechanism suggests new ways to bolster immunity to deadly rotavirus: U of T researchers – News@UofT

Researchers at the University of Toronto have discovered how a brief disruption to a molecular pathway in the guts of mice before they are born can compromise immunity in adulthood to a common and often deadly intestinal virus.

The researchers found that in utero inhibition of molecular signalling in the lymphotoxin pathway, long known as important in the development of the immune system, prevented a robust antibody response in adult mice to rotavirus. In humans, rotavirus causes an estimated 215,000 deaths annually, mostly in the developing world.

That early disruption limits the ability of the immune system to later trigger and generate production of Immunoglobulin A (IgA) antibodies, the researchers showed. It also interferes with the nature and function of cells in the gut that support the antibody response, called mesenteric lymph node stromal cells.The research was recently published in the journal Science Immunology.

It was surprising that these non-immune stromal cells were so important to the immune response, saysJennifer Gommerman, a professor ofimmunologyin U of Ts Faculty of Medicine and principal investigator on the study.

It turns out that stromal cells affect the ability of immune B cells to produce IgA that neutralizes rotavirus. Were just beginning to understand the influence these stromal cells can have.

Gommerman says the findings highlight the growing importance of research on the environment in which immune cells function. We typically think of a lymph node as just a bag of lymphocytes, but there is also this supporting structure that clearly has an active role in shaping immunity.

The studys first author, post-doctoral researcherConglei Li, identified a broad subset of stromal cells that affect the immune response to rotavirus. But the key players are likely a subset of that subset, Gommerman says. New technology known as single-cell RNA sequencing should soon enable researchers to identify many more of those cells, she adds.

That work could, in turn, lead to a better understanding of the genetic and environmental factors that may undermine immunity to rotavirus in the developing world, where rotavirus vaccines are much less effective than in high-resource settings.

Gommerman says that while several dysfunctions in the immune system likely contribute to reduced immunity to rotavirus in low-income countries, the current study offers a hint that prevention may be possible.

The thinking would be that if youre pregnant in a resource-depleted area, you may take a dietary supplement at a specific point to ensure proper development of tissues that support immunity, and which enable a vaccine to be more effective, she says.

That kind of intervention is likely a long way off, adds Gommerman, and replicating her results in human pregnancy presents obvious ethical problems. A more immediate next step for her lab is a collaborative study on IgA immune responses to other pathogens such as norovirus, another highly contagious disease.

A focus on single pathogens is useful in studies of IgA, according to Gommerman, because so many factors can influence IgA response. If you simplify the system of study, you get more predictable kinetics and can ask more discrete questions, she says. Weve made a contribution with that approachon a question that has been percolating in several labs for years. That feels good.

The research received support from the Canadian Institutes of Health Research, Princess Margaret Cancer Foundation and the Swiss National Science Foundation.

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Molecular mechanism suggests new ways to bolster immunity to deadly rotavirus: U of T researchers - News@UofT

Immunology

of T, international researchers focus on ‘surprisingly high’ incidence of chronic pain in adolescents – News@UofT

An international research collaboration has been awarded a $9-million research grant from the U.S. National Institutes of Health to tackle the complex problem of chronic musculoskeletal pain in adolescents.

The five-year research project, involving two distinct phases and an international team of researchers from the University of Toronto, the Hospital for Sick Children, Stanford University and Cincinnati Childrens Hospital, will work towards uncovering a biological signature for chronic pain, helping those for whom traditional therapies arent effective.

International in scope and global in its potential impact, the project represents an unprecedented opportunity to perform vital research on a largely unstudied population.

This is the first pediatric study of this magnitude, says project co-investigator Jennifer Stinson, professor in U of Ts Lawrence S. Bloomberg Faculty of Nursing and a nurse practitioner at the chronic pain clinic at the Hospital for Sick Children.

The study will shed light on a phenomenon not well understood. Up to five per cent of adolescents thats 3.5 million in the U.S. alone suffer from chronic musculoskeletal pain. The pain can stem from anything from injuries to juvenile fibromyalgia and Ehlers-Danlos Syndrome, a condition affecting connective tissues in the body.

Childrens chronic pain is really, really underappreciatedin that the incidence of it is surprisingly high, but the awareness of it is surprisingly low, says co-investigator Robert Coghill, director of the Center for Understanding Pediatric Pain and professor of pediatrics at Cincinnati Childrens Hospital Medical Center.

Not all pain is the same, though: A staggering 40 to 60 per cent of sufferers will be considered treatment-resistant. Those adolescents quickly grow into adults with chronic, untreatable pain. But by looking at chronic pain through an array of angles brain imaging, quantitative sensory testing, immunology and psychology the researchers hope to pinpoint which adolescents will or wont respond to treatments, and what underlying factors may be at work in those outcomes.

The first phase of the project will gather these types of data from 250 adolescents aged 14 to 18 who suffer from chronic musculoskeletal pain.

if we are able to capture enough measures across a whole slew of domains, we can then use unbiased machine learning and [big data] algorithms to predict whether patients will respond to treatment or not, explains Massieh Moayedi, assistant professor at U of Ts Faculty of Dentistry, a co-investigator who brings expertise in pain and brain imaging to the project.

A multimodal biomarker will allow us to classify those who are at high risk for pain persistence.

If successful at pinpointing a chronic pain signature, a second phase of the study will commencein which data from a second cohort of 125 adolescent recruits will help validate the pain signature.

This project is really unique, says Stinson, who also leads the iOuch lab at Sick Kids. If we can actually find this biological signature, we have a chance to do more precision medicine based on the phenotype of that child. Well be able to better tailor treatment.

Laura Simons, a psychologist and associate professor at Stanford University with expertise in psychological factors influencing childrens pain, will lead the study.

Im very excited about the immune profiling, says Simons, pointing to a burgeoning field of study that looks at the behaviour of immune cells after trauma or medical interventions such as surgery.

Equally, Simons is curious to see whether some of our pen and pencil measures [of psychology] will rise to the top, to see whether they are as informative as more invasive measures.

While each of the teams will perform their series of tests on their adolescent recruits, Stanford University and the Stanford University Medical Centre will additionally collate data and perform data analysis on the results. The data will remain at Stanford, where the researchers will begin collating one of the worlds largest biobanks of multimodal paediatric pain data for future studies.

Patient recruitment for phase one of the study begins as early as this month.

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of T, international researchers focus on 'surprisingly high' incidence of chronic pain in adolescents - News@UofT

Immunology

30 babies in Bracknell have missed their vital ‘six in one jabs’ – Bracknell News

DOZENS of Bracknell Forest babies have missed out on important jabs which protect them from potentially deadly illnesses, figures reveal.

The British Society for Immunology has urged the new government to deliver on its promise to develop the UKs first vaccine strategy to protect communities against nasty diseases.

READ THIS: Bad parking - Bracknell News readers send in pictures

Young children should get the so-called six-in-one jab, which protects against six serious infections including polio, whooping cough and diphtheria, in the first few months of their lives.

Public Health England data shows that 30 children in Bracknell Forest who had their first birthday in the six months to September missed out on the vaccination.

But 95.9 per cent of one year olds did have it, meaning the area was above the 95 per cent rate recommended by the World Health Organisation to prevent outbreaks.

The uptake rate for the South East over the period was 93.2 per cent, while the figure across England stood at 92.1 per cent.

The British Society for Immunology said the uptake rate across England for the six-in-one vaccine among one year olds has averaged around 92 per cent over the past year.

ALSO READ: Girls born in Bracknell Forest face more than a dozen years of poor health in old age

Dr Doug Brown, the groups chief executive, said: Low levels of vaccination coverage matter as it means these diseases have the potential to spread within our communities, infecting unvaccinated people, with young babies and people with compromised immune systems particularly at risk.

We urge the new government to deliver on its promise to develop the UKs first vaccine strategy and to fully fund immunisation services to ensure our communities are protected against these preventable diseases.

But he also urged parents to make sure their children get the jabs.

He added: If you are worried your child hasnt received all the doses of the six-in-one vaccine, do make an appointment at your GP surgery.Its much better to get your child vaccinated than risk them catching one of these nasty diseases.

Babies should have three rounds of the six-in-one vaccination at eight, 12 and 16 weeks of age.

READ MORE: Home in Binfield for sale over 1.5 MILLION

It helps them develop a strong immunity to diphtheria, hepatitis B, haemophilus influenza type b, polio, tetanus and whopping cough all described by the NHS as serious childhood diseases.

Nicola Blackwood, Health minister said: Every child must be vaccinated against dangerous and potentially fatal diseases. Vaccine uptake is very high, at around 90 per cent, for most childhood vaccines, but we are determined to drive rates up even further.

"Our new vaccination strategy, published in the new year, will consider a range of approaches to improve uptake.

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30 babies in Bracknell have missed their vital 'six in one jabs' - Bracknell News

Immunology

Single dose of antibody-based treatment can beat HIV in newborn babies – News-Medical.net

A single dose of an antibody-based treatment can prevent HIV transmission from mother to baby, new nonhuman primate research suggests for the first time. The findings are being published in the journal Nature Communications.

When that single dose is given is key, however. The study found rhesus macaque newborns did not develop the monkey form of HIV, called SHIV, when they received a combination of two antibodies 30 hours after being exposed to the virus.

Delaying treatment until 48 hours, on the other hand, resulted in half of the baby macaques developing SHIV when they were given four smaller doses of the same antibody cocktail. In comparison, the study found macaques that received the current standard HIV treatment - antiretroviral drugs - remained SHIV-free when they started a three-week regimen of that therapy 48 hours after exposure.

These promising findings could mean babies born to HIV-positive mothers can still beat HIV with less treatment."

Nancy Haigwood, Ph.D., study's corresponding's author, professor of pathobiology and immunology in the Oregon Health & Science University School of Medicine, as well as the director at the Oregon National Primate Research Center at OHSU

This is the first time a single dose of broadly neutralizing antibodies given after viral exposure has been found to prevent SHIV infection in nonhuman primate newborns. Previous research by Haigwood, Ann Hessell, Ph.D., and others showed four doses of antibodies started 24 hours after exposure prevented SHIV infection, with all 10 of the baby primates in that study not having any SHIV virus for six months. Both studies used a combination of two antibodies called PGT121 and VRC07-523.

The new study also suggests a much shorter course of antiretroviral therapy given after virus exposure could prevent HIV transmission to newborns. Human babies born from HIV-positive mothers typically take the drug cocktail - a personalized regimen of multiple drugs taken daily - for about six weeks before being re-tested. If the tests are then positive, they likely need to take HIV drugs for the rest of their lives. But this study showed nonhuman primate newborns didn't have SHIV after undergoing antiretroviral therapy for just three weeks starting 48 hours after exposure.

HIV-positive women typically take antiretroviral therapy drugs during pregnancy for their own health, as well as to prevent passing the virus onto their developing child. But mother-to-baby transmission sometimes still happens. Children born to HIV-positive mothers also are given antiretroviral therapy to further prevent infection. However, this drug cocktail can have many negative side effects, involves making special liquid formulations for newborns, and researchers worry about antiretroviral therapy's long-term consequences for development.

Antibodies, however, aren't toxic and can be modified to last a long time in the body, which reduces treatment frequency. This has led researchers to explore their potential to replace or supplement antiretroviral therapy for newborns with HIV-positive mothers as well as for HIV-positive adults.

Next, Haigwood and colleagues plan to see if different antibodies, or a combination of antibodies and antiretroviral therapy, could be even more effective. They also want to determine if the antibodies they evaluate actually eliminate HIV, or only prevent it from replicating.

The research team has regularly shared their primate research findings with the scientific community, including those involved in the International Maternal Pediatric Adolescent AIDS Clinical Trials Network, which is currently leading two trials evaluating a single antibody to treat HIV-exposed newborns.

Source:

Journal reference:

Shapiro, M.B., et al. (2020) Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity. Nature Communications. doi.org/10.1038/s41467-019-13972-y.

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Single dose of antibody-based treatment can beat HIV in newborn babies - News-Medical.net

Immunology

Invest With A Purpose: Own The Future With Megatrend ETFs – Forbes

We now drive electric cars, watch our favorite shows on mobile devices, attend concerts via virtual reality and control the temperature in our homes by giving instructions to a voice assistant.

Technological innovations like these underpin the transformative forces that are changing how we live and work.

You can harness the growth potential of these powerful forces by investing in megatrend ETFs.

An ETF (exchange-traded fund) is a diversified collection of securities (like a mutual fund) that trades on an exchange (like a stock). Megatrend ETFs capture targeted groups of stocks perceived to be well-positioned to benefit from shifts in technology, society, the environment and demographics over time.

Here's why megatrend ETFs are the next frontier of access and a glimpse at the five megatrends BlackRock sees at the forefront of our changing world.

With megatrend ETFs, iSharesBlackRock's ETF businessoffers individual investors access to opportunities that were once available primarily to institutional investors able to qualify for venture capital, private equity and other private market investments.

This is unlike sector indexes (like Technology or Communications) that more rigidly track companies within a single sector, or broad indexes (like the S&P 500) that track a universe of companies across many industries and are weighted heavily toward larger, more established companies rather than smaller, more disruptive players.

As an example, with megatrend ETFs, investment in the self-driving and electric vehicles trend would go beyond carmakers and also include hardware companies that make road-monitoring sensors, software companies that make the algorithmic "brains" required to guide vehicles as well as battery producers. By looking beyond sectors and regions and selecting companies that are leaders in a particular ecosystem, investors can access the full growth potential underpinning these trends.

Megatrend ETFs are also transparent and easy to own, removing the need to pick single-stock winners, which has proved difficult for investors to successfully do. With the potential to capture long-term growth opportunities, megatrend ETFs can be seen as complementary holdings to your core portfolio.

BlackRock has identified five megatrends shaping our future. Here's a look at each and how they can help position you for tomorrow.

Technology is such a prevalent force that the current era has been dubbed the Fourth Industrial Revolution. How you live and work is shaped by exponential technologies like artificial intelligence, 3D printing and synthetic biology, to name just a few. Technology is driving exponential progress in the tech sector and far beyond and underpins the other megatrends we'll mention shortly.

You can tap into the firms harnessing technology to solve privacy threats by investing in iShares Cybersecurity and Tech ETF.1 The fund seeks to track the investment results of an index composed of companies involved in cybersecurity and technology, including cybersecurity hardware, software, products and services.

Longer lifespans and modern lifestyles will change medicine and consumer habits. If you are fascinated by the possibilities of medical technology, consider ETFs that target companies at the forefront of medical progress. iShares Genomics Immunology and Healthcare ETF2 is one such option. This ETF seeks to track the investment results of an index composed of companies that could benefit from the long-term growth and innovation in personalized medicine: genomics, immunology and bioengineering.

It's expected that more than two-thirds of the world's population will reside in cities by 2050, double the percentage from 1950.3 This mass migration to cities will require new business models and infrastructure.

If you would like to invest in companies that may benefit from this megatrend, consider iShares U.S. Infrastructure ETF.4 The fund seeks to track the investment results of an index composed of equities of U.S. companies that have infrastructure exposure and could benefit from a potential increase in domestic infrastructure activities. This ETF offers access to two groups of infrastructure companies that are equally weighted: owners and operators, such as railroads and utilities, and enablers, such as materials and construction companies.

Demand for a clean, green tomorrow will advance energy and conservation. If you drive, or would like to drive, an electric car, you may be interested in putting your money in an ETF with an environmental focus. iShares Self-Driving EV and Tech ETF5 seeks to track the investment results of an index composed of companies that may benefit from growth and innovation in and around electric vehicles, battery technologies and autonomous driving technologies.

It's expected that the number of newly affluent consumers will expand in Asia and across emerging markets. For example, China now has 3.5 million millionaires and more residents with wealth above $50 million than any country except the United States.6 iShares MSCI China A ETF7 can provide access to the Chinese market as it tracks the investment results of an index composed of domestic Chinese equities that trade on the Shanghai or Shenzhen Stock Exchange and are not well-represented in broad benchmarks.

Every day, you witness how megatrend-driven innovations are transforming our world. With iShares megatrend ETFs, you can invest in the future today.

For more information on how ETFs can help you invest in our changing world, click here.

Carefully consider the Funds' investment objectives, risk factors, and charges and expenses before investing. This and other information can be found in the Funds' prospectuses or, if available, the summary prospectuses, which may be obtained by visiting http://www.iShares.com or http://www.blackrock.com. Read the prospectus carefully before investing.

Investing involves risk, including possible loss of principal.

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Invest With A Purpose: Own The Future With Megatrend ETFs - Forbes

Anatomy

Greys Anatomy Taps Shameless Alum Richard Flood as the New Karev – Sunriseread

RELATED STORIES

A Flood warning has gone into impact at Gray Sloan Memorial.

Shameless vet Richard Flood (get it?) is becoming a member of Grays Anatomy in the recurring function of Dr. Cormac Hayes, the new head of Pediatric Surgical procedure at Gray Sloan. Dr. Hayes is introduced in to fill the void left by Justin Chambers Karev.

As followers of the venerable ABC medical drama know, Karev was sacked in final seasons finale, and has since segued to Pacific Northwest Basic Hospital (the place hes working with Richard, who additionally received fired from Gray Sloan). Floods first episode is about to air later this season.

On Shameless, Flood performed the boyfriend of Emmy Rossums Fiona in Seasons eight and 9. Though present Grays showrunner Krista Vernoff beforehand served as an exec producer on Shameless, her stint didnt overlap with Floods.

Our sister web site Deadline broke the information of Floods casting.

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Greys Anatomy Taps Shameless Alum Richard Flood as the New Karev - Sunriseread

Anatomy

Should This Be ‘Grey’s Anatomy’s’ Last Season’? – The Blast

And there's also another theory that ties into whether or not the series should pull the plug and move onto the afterlife of reruns.

Over the years, the primary characters of Greys Anatomy learned surgical techniques and hospital protocol while enduring a countless array of calamities, including bomb threats, plane crashes, and hospital fires, explains PopSugar.Now that the lead characters have aged well beyond medical school, theres not nearly as much teaching going on as there was in the first three seasons. And that may be the key to saving the show.

Even lead actress Ellen Pompeo has admitted that it's time to shake things up on the show, but whether or not her suggestions are taken seriously is it already too late? Only time will tell.

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Should This Be 'Grey's Anatomy's' Last Season'? - The Blast

Anatomy

Actors who actually hate their own shows or have snubbed them – INSIDER

Katherine Heigl once took herself out of the running for an award for "Grey's Anatomy."

In a move that reportedly angered producers, ABC's "Grey's Anatomy" star Katherine Heigl voluntarily opted out of the 2008 Emmy race after winning the previous year's award for best supporting actress in a drama series.

"I did not feel that I was given the material this season to warrant an Emmy nomination and in an effort to maintain the integrity of the academy organization, I withdrew my name from contention," Heigl said in a statement that was first given to former Los Angeles Times blog, Gold Derby, according to The New York Times.

"In addition, I did not want to potentially take away an opportunity from an actress who was given such materials," Heigl added.She left the medical drama in 2010.

Chace Crawford once said he'd have to look for his dignity after leaving "Gossip Girl."

Chace Crawford starred on The CW hit "Gossip Girl" for years, but he's since implied that his role as Nate Archibald took away his dignity.

In a 2012 interview with Us Weekly, Crawford joked that leaving "Gossip Girl" would mean tracking down his lost dignity.

"I'm gonna look for my dignity," he said. "My dignity is somewhere on set. I think it happened around season two. Leading into season three, it was all out the window."

Penn Badgley has also seemingly dissed his time on "Gossip Girl."

In a 2013 interview with Salon, actor Penn Badley shared his excitement about his role in the drama film "Greetings from Tim Buckley" while seemingly snubbing his past work, which largely includes his break-out role The CW's "Gossip Girl."

"To be proud of something is a really nice feeling," he said, referring to his role in the 2013 film. "And it's a new feeling, and it's something that I wanna keep going with. I can walk a little taller feeling that I don't have to be constantly apologizing for the work that I've done in the past."

And, back in 2011, while at a Sundance Film Festival press event for his film "Margin Call," am New York reported that Badgley said his first response to landing a role in it was, "Are you sure you want me? Have you seen 'Gossip Girl?'"

Per the publication, he also said that the film is "hopefully the beginning of what I'm really aiming for, which is really, actually, acting."

The late Robert Reed has said he doesn't want to be remembered as the dad on "The Brady Bunch."

Actor Robert Reed famously played the patriarch of the Brady family on ABC's "The Brady Bunch," but he's said he doesn't want to be remembered for his role on the cult-classic sitcom.

In a 1992 interview with People before his death that same year, Reed spoke of how being "classically trained and well-educated" made it difficult for him to take the series seriously.

"It was just as inconsequential as can be," Reed said of the show. "To the degree that it serves as a babysitter, I'm glad we did it. But I do not want it on my tombstone."

Evangeline Lilly has said she was disappointed by the plot of "Lost" and her character's storyline.

In an interview with the "Lost Boys" podcast, Evangeline Lilly expressed disappointment in her time playing mysterious castaway Kate Austen on the ABC drama "Lost."

The actress said that she was disappointed with the show's plot and her own character's storyline, which she described as centering around her romantic relationships with other characters.

"There's nothing wrong with women's lives being characterized by relationships, and I think that happens to men and women," Lilly told the podcast. "But there was this eventual lack of dimension to what was going on with her."

"I did throw scripts across rooms when I would because I would get very frustrated by the diminishing amount of autonomy that she had and the diminishing amount of her own story there was to play," she added.

Lilly also said that she felt pressured into filming partially nude scenes on two separate occasions, with the scenes making her feel so uncomfortable that she trembled and cried.

The actress said she subsequently refused to participate in any other nude scenes during her time on "Lost."

Angus T. Jones of "Two and a Half Men" later said he thought the show was "filth."

The CBS sitcom "Two and a Half Men" featured child star Angus T. Jones as the young Jake Harper. Now, as an adult,Jones has been vocal about his dislike of the show's content and television in general.

"If you watch 'Two and a Half Men,' please stop watching 'Two and a Half Men.' I'm on 'Two and a Half Men,' and I don't want to be on it. Please stop watching it and filling your head with filth," Jones stated during a testimonial for the Forerunner Christian Church in 2012.

In the video interview, Jones goes on to explain that he also believes that, in general, watching television is unhealthy for one's brain.

Shannen Doherty reportedly called "Charmed" a "show for 12-year-olds."

After rocketing to fame through her work in the 1988 film "Heathers" and nabbing a breakout role as Brenda Walsh on the TV show "Beverly Hills, 90210," Shannen Doherty joined the cast of the 1998 hit WB series "Charmed" as witch Prue Halliwell.

However, co-star Alyssa Milano has said that Doherty was reportedly quick to clash with fellow cast members on the show.

As Milano told Entertainment Weekly in 2001, Doherty abruptly left "Charmed" at the end of its third season and subsequently dismissed the program as "a show for 12-year-olds."

Milano expressed frustration at the nature of Doherty's exit, telling the publication, "I think it's unfortunate that she left, and that she needed to bad-mouth everyone involved and the audience."

Jackie Gleason once delivered an on-air apology for his game show being a "flop."

Jackie Gleason was the host of "You're In the Picture," a game show that premiered in 1961 and continued in its original format for just a single episode.

Following the series' disastrous premiere, Gleason opened the second episode by directly apologizing to viewers.

"Last week, we did a show called 'You're in the Picture' that laid, without a doubt, the biggest bomb. I'm telling you friends that I've seen bombs in my day. This would make the H-bomb look like a two-inch salute," Gleason said on-air.

He went on to explain and examine the reasons the first episode was so bad, musing that he didn't understand "how it was possible for a group of trained people to put on so big a flop."

From the second episode onward, the show was reformatted as "The Jackie Gleason Show: The American Scene Magazine" and took on a talk-show format.

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Actors who actually hate their own shows or have snubbed them - INSIDER