Category Archives: Gene Medicine

Text Size:A- A+

When some people become infected with the coronavirus, they only develop mild or undetectable cases of COVID-19. Others suffer severe symptoms, fighting to breathe on a ventilator for weeks, if they survive at all.

Despite a concerted global scientific effort, doctors still lack a clear picture of why this is.

Could genetic differences explain the differences we see in symptoms and severity of COVID-19?

To test this, we used computer models to analyze known genetic variation within the human immune system. The results of our modeling suggest that there are in fact differences in peoples DNA that could influence their ability to respond to a SARS-CoV-2 infection.

When a virus infects human cells, the body reacts by turning on what are essentially anti-virus alarm systems. These alarms identify viral invaders and tell the immune system to send cytotoxic T cells a type of white blood cell to destroy the infected cells and hopefully slow the infection.

But not all alarm systems are created equal. People have different versions of the same genes called alleles and some of these alleles are more sensitive to certain viruses or pathogens than others.

To test whether different alleles of this alarm system could explain some of the range in immune responses to SARS-CoV-2, we first retrieved a list of all the proteins that make up the coronavirus from an online database.

We then took that list and used existing computer algorithms to predict how well different versions of the anti-viral alarm system detected these coronavirus proteins.

Also read: Worlds most accurate antibody test has arrived. Or has it?

The part of the alarm system that we tested is called the human leukocyte antigen system, or HLA. Each person has multiple alleles of the genes that make up their HLA type. Each allele codes for a different HLA protein. These proteins are the sensors of the alarm system and find intruders by binding to various peptides chains of amino acids that make up parts of the coronavirus that are foreign to the body.

Once an HLA protein binds to a virus or piece of a virus, it transports the intruder to the cell surface. This marks the cell as infected and from there the immune system will kill the cell.

In general, the more peptides of a virus that a persons HLAs can detect, the stronger the immune response. Think of it like a more sensitive sensor of the alarm system.

The results of our modeling predict that some HLA types bind to a large number of the SARS-CoV-2 peptides while others bind to very few. That is to say, some sensors may be better tailored to SARS-CoV-2 than others. If true, the specific HLA alleles a person has would likely be a factor in how effective their immune response is to COVID-19.

Because our study only used a computer model to make these predictions, we decided to test the results using clinical information from the 2002-2004 SARS outbreak.

Whats next?

We found similarities in how effective alleles were at identifying SARS and SARS-CoV-2. If an HLA allele appeared to be bad at recognizing SARS-CoV-2, it was also bad at recognizing SARS. Our analysis predicted that one allele, called B46:01, is particularly bad with regards to both SARS-CoV-2 and SARS-CoV. Sure enough, previous studies showed that people with this allele tended to have more severe SARS infections and higher viral loads than people with other versions of the HLA gene.

Based on our study, we think variation in HLA genes is part of the explanation for the huge differences in infection severity in many COVID-19 patients. These differences in the HLA genes are probably not the only genetic factor that affects severity of COVID-19, but they may be a significant piece of the puzzle. It is important to further study how HLA types can clinically affect COVID-19 severity and to test these predictions using real cases. Understanding how variation in HLA types may affect the clinical course of COVID-19 could help identify individuals at higher risk from the disease.

To the best of our knowledge, this is the first study to evaluate the relationship between viral proteins across a wide range of HLA alleles. Currently, we know very little about the relationship between many other viruses and HLA type. In theory, we could repeat this analysis to better understand the genetic risks of many viruses that currently or could potentially infect humans.

Austin Nguyen, PhD Candidate in Computational Biology and Biomedical Engineering, Oregon Health & Science University; Abhinav Nellore, Assistant Professor of Biomedical Engineering & Surgery, Oregon Health & Science University, and Reid Thompson, Assistant Professor of Radiation Medicine, Oregon Health & Science University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Also read: After HCQ, its time for azithromycin and pneumonia drug combo to go under clinical trial

ThePrint is now on Telegram. For the best reports & opinion on politics, governance and more, subscribe to ThePrint on Telegram.

Subscribe to our YouTube channel.

Continue reading here:
Its in your genes Whether Covid lands you in hospital or not depends on your body - ThePrint

The COVID-19 pandemic has wrecked havoc on several major industries this year. However, the healthcare sector has been one of the few bright spots in this rather ugly market. A wide swath of the healthcare space, in fact, is in positive territory for the year right now.

Generally speaking, investors have flocked to these companies because of their somewhat unique ability to continue to operate during this ongoing pandemic. Not many businesses outside of healthcare and technology can make that claim.

Which healthcare stocks have the best chance of pushing even higher over the course of May?AbbVie (NYSE:ABBV),Adverum Biotechnologies (NASDAQ:ADVM), andHeron Therapeutics (NASDAQ:HRTX) are three names healthcare investors will definitely want to keep their eyes on this month. Here's why.

Image source: Getty Images.

AbbVie is a large-cap biopharma company. The company's shares are worth checking out this month for two core reasons. First and foremost, AbbVie is slated to close on its $63 billion acquisition of Allerganbefore the end of May. This mega-merger will greatly diversify AbbVie's product portfolio, lowering the risk associated with the eventual decline of the company's anti-inflammatory medicine, Humira.

Secondly, AbbVie's brand-new immunology medicines Skyrizi and Rinvoq, and its blood cancer franchise consisting of Imbruvica andVenclexta, are all exceeding expectations at the moment. These four key products, in fact, helped AbbVie to handily beat Wall Street's first-quarter revenue estimate earlier this month.

AbbVie's shares have yet to truly benefit from these positive tailwinds, though. As proof, the company's stock is presently trading at less than nine times forward-looking earnings. That's a dirt-cheap valuation for a blue-chip biopharma stock, especially for one that pays a sky-high annualized yield of 5.53% at current levels. So, if you're on the hunt for a grossly undervalued growth and income vehicle, AbbVie should definitely be at the top of your list this month.

Adverum is a clinical-stage gene therapy company. The biotech's shares have gained 71% so far this year due to an encouraging clinical update for itswet age-related macular degeneration (wet AMD) candidate ADVM-022. ADVM-022 is designed to be a one-and-done gene therapy for wet AMD. Currently, patients with this serious eye disorder have to receivefrequent anti-VEGF injections simply to slow the progression the disease. Adverum's therapy could thus prove to be a game-changer for this condition.

What's the opportunity? Theanti-VEGF injection market for wet AMD is a multibillion-dollar space. Adverum's experimental therapy thus has the real potential to morph into a megablockbuster product by the end of the decade. The drawback with this small-cap biotech stock is that ADVM-022 is still in the early stages of development, meaning it could take several more years before Adverum books any sales for this high-value product candidate.

That being said, Adverum might have a big target on its back on the heels of this data release. Gene therapies are highly sought-after products, and ADVM-022 is targeting an enormous market in wet AMD. Adverum, in turn, may already be fielding buyout or partnering offers. Regardless, this small-cap biotech stock comes across as woefully undervalued based on ADVM-022's commercial opportunity.

Heron is an early commercial stage biopharma. The company currently markets two drugs indicated for chemotherapy-induced nausea and vomiting. But the real star of the show is the experimental postoperative pain medication HTX-011. Wall Street's peak sales for this pain drug presently range from a low of $545 million to a high of $1 billion. To put these revenue projections into context, Heron's market cap presently stands at a mere $1.33 billion.

What's the lowdown? The FDA's target review date for HTX-011 is set forJune 26, 2020. The agency could still delay a final decision due to the COVID-19 pandemic, but Heron seems to think the FDA will ultimately stick by this goal date.

The big picture is that HTX-011 -- if approved in a timely manner -- should super-charge Heron's top line over the next 10 years. This small-cap biotech stock, in turn, could be on the cusp of a major growth spurt in the second half of 2020.

What's the risk? Regulatory decisions are impossible to handicap. So, while Heron's stock does sport a juicy upside potential, investors probably shouldn't go hog-wild with this name ahead of this risky binary event. A smallish position, though, may be worth the risk.

The rest is here:
3 Best Healthcare Stocks to Buy in May - The Motley Fool

CRANBURY, N.J., May 06, 2020 (GLOBE NEWSWIRE) -- Amicus Therapeutics (Nasdaq: FOLD) a global, patient-dedicated biotechnology company focused on discovering, developing and delivering novel medicines for rare diseases today announced the acceptance of several abstracts for presentation at the American Society of Gene & Cell Therapy 23rd Annual Meeting being held virtually on May 12 15. Preclinical data from its Pompe gene therapy program, which Amicus is developing with the Gene Therapy Program of the Perelman School of Medicine at the University of Pennsylvania, will be presented as an oral presentation. Preclinical data related to the CLN6 and CLN8 Batten disease programs, with our partners at Sanford Research and Nationwide Childrens Hospital, will be presented in respective posters.

Oral Platform Presentation: Thursday, May 14, 2020,4:45-5:00p.m. ET

Pompe Disease:

Poster Session: Tuesday, May 12, 2020, 5:30-6:30 p.m. ET

CLN6 Batten Disease:

Poster Session: Wednesday, May 13, 2020, 5:30-6:30 p.m. ET

CLN8 Batten Disease:

All abstracts for the American Society of Gene & Cell Therapy 23rd Annual Meeting are now available online.

About Pompe DiseasePompe disease is an inherited lysosomal disorder caused by deficiency of the enzyme acid alpha-glucosidase (GAA). Reduced or absent levels of GAA leads to accumulation of glycogen in cells, which results in the clinical manifestations of Pompe disease. The disease can be debilitating and is characterized by severe muscle weakness that worsens over time. Pompe disease ranges from a rapidly fatal infantile form with significant impacts to heart function to a more slowly progressive, late-onset form primarily affecting skeletal muscle. It is estimated that Pompe disease affects approximately 5,000 to 10,000 people worldwide.

About Batten DiseaseBatten disease is the common name for a broad class of rare, fatal, inherited disorders of the nervous system also known as neuronal ceroid lipofuscinoses, or NCLs. In these diseases, a defect in a specific gene triggers a cascade of problems that interferes with a cells ability to recycle certain molecules. Each gene is called CLN (ceroid lipofuscinosis, neuronal) and given a different number designation as its subtype. There are 13 known forms of Batten disease often referred to as CLN1-8; 10-14. The various types of Batten disease have similar features and symptoms but vary in severity and age of onset.

Most forms of Batten disease/NCLs usually begin during childhood. The clinical course often involves progressive loss of independent adaptive skills such as mobility, feeding, and communication. Patients may also experience vision loss, personality changes, behavioral problems, learning impairment, and seizures. Patients typically experience progressive loss of motor function and eventually become wheelchair-bound, are then bedridden, and die prematurely.

About Amicus Therapeutics Amicus Therapeutics (Nasdaq: FOLD) is a global, patient-dedicated biotechnology company focused on discovering, developing and delivering novel high-quality medicines for people living with rare metabolic diseases. With extraordinary patient focus, Amicus Therapeutics is committed to advancing and expanding a robust pipeline of cutting-edge, first- or best-in-class medicines for rare metabolic diseases. For more information please visit the companys website at http://www.amicusrx.com, and follow us on Twitter and LinkedIn.

Forward-Looking StatementsThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 relating to preclinical and clinical development of our product candidates. The inclusion of forward-looking statements should not be regarded as a representation by us that any of our plans or projections will be achieved. Any or all of the forward-looking statements in this press release may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. For example, with respect to statements regarding results of preclinical studies and clinical trials, actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in our business, including, without limitation: the potential that results of clinical or preclinical studies indicate that the product candidates are unsafe or ineffective; the potential that preclinical and clinical studies could be delayed because we identify serious side effects or other safety issues; the potential that we may not be able to manufacture or supply sufficient clinical products; and the potential that we will need additional funding to complete all of our studies and manufacturing. Further, the results of earlier preclinical studies and/or clinical trials may not be predictive of future results. In addition, all forward-looking statements are subject to other risks detailed in our Annual Report on Form 10-K for the year ended December 31, 2019. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, and we undertake no obligation to revise or update this press release to reflect events or circumstances after the date hereof.

CONTACTS:

Investors/Media:Amicus TherapeuticsAndrew FaughnanDirector, Investor Relationsafaughnan@amicusrx.com(609) 662-3809

FOLDG

Read the rest here:
UPDATE Amicus Therapeutics Announces Upcoming Presentations at the American Society of Gene & Cell Therapy 23rd Annual Meeting - GlobeNewswire

For people with rare diseases, a single gene therapy treatment could restore normal function and alleviate the burden of ongoing care, as Dr Ian Winburn tells Kennas Fitzsimons

Dr Ian Winburn

Gene therapy is the next generation of medicine that targets the underlying cause of genetic diseases. It has the potential to offer patients a really transformational clinical benefit and improve quality of life.

Thats according to Dr Ian Winburn, Global Medical Lead, Haemophilia, Endocrine and Inborn Errors of Metabolism (IEM), Rare Diseases, Pfizer Biopharmaceuticals Group. Dr Ian Winburn, Global Medical Lead, Haemophilia, Endocrine and IEM, Pfizer Biopharmaceuticals Group, pictured right during his presentation on gene therapy at BioPharma Ambition held in Dublin Castle on March 4. Pic: Conor McCabe Photography.

Formerly a clinician in the UK National Health Service (NHS), Dr Winburn trained in general surgery and completed a PhD on novel drug discovery in renal transplantation before moving into industry 10 years ago, where he worked in the area of inflammation and immunology before leading the European haemophilia team.

Dr Winburn is now working to develop innovative gene therapies with the potential to restore normal function to patients with rare diseases, possibly with just a single treatment, changing the way people manage their disease.

Gene therapy: What is it?Gene therapy uses genes as medicine. It works by introducing functioning copies of missing or defective genes into the body and can target the underlying cause of a disease at the cellular level.

There are various types of gene therapies, such as the gene editing technique, CRISPR (clustered regularly interspaced short palindromic repeats), as well as epigenetic approaches that look at ways in which genes may be turned on or turned off.

Pfizer Rare Disease is focusing on an in-vivo approach that utilises a recombinant adeno-associated virus (AAV) to deliver the gene therapy.

This approach works by targeting the missing or non-functional gene in an individuals DNA and adding a copy of it with a functioning gene that, in turn, produces a functioning protein.

The functioning gene serves as a blueprint for the tissue to create the missing or non-functioning protein that is causing a disease.

Dr Winburn said: Gene therapy is in the branch of genetic medicine, where you can think about approaches that look to add a gene to a host cell, and that gene goes on and codes for a protein. That protein its coding for can replace a missing protein. So, in the example of haemophilia, where theres a missing factor VIII or factor IX clotting factor, that protein that is either missing or is faulty could be essentially administered through a gene therapy. A gene is added to a host cell that codes for the factor VIII or factor IX and therefore replaces that protein.

The functioning gene is delivered directly to the targeted cells by means of a highly specialised viral vector. This vector, effectively, is the package that contains the gene. In simple terms, it can be likened to the cardboard boxes that online retailers use to ship products.

The manufactured vectors are protein shells modelled after viruses in which all infectious viral components have been removed, and a functioning gene is added. Different viral vectors are used to reach specific tissues in the body, such as the liver or muscle.

VectorVector is a great word because vector describes a direction, by definition, and the other way we can think about vector is a vector often carries something. There are a few approaches you can use to develop a vector. We have embraced an AAV vector that has the capacity to deliver the transgene, the gene that is going to be added to the host somatic cell. In the case of haemophilia, it is targeted at the liver, Dr Winburn says.

Rare diseases focusAbout 280 million people worldwide live with a genetic disease, and more than 80 per cent of rare diseases are genetic in origin, according to Pfizer. For people born with rare diseases, the burden of disease management can be huge. Treatment is often ongoing and may be lifelong. Gene therapy could enable patients to live without the need for ongoing treatment. This raises the prospect of relief not only from symptoms but also from the burden of disease management.

Dr Winburn elaborates on the reasons why gene therapy approaches are currently focused specifically on rare diseases that have single-gene alterations.

It tends to be rare genetic diseases that are monogenic in nature Some of the more common diseases are very much multifactorial in origin: there may be a genetic component but there are other aspects to their aetiology rather than these single, monogenic conditions that gene therapy really lends itself to.

The other aspect is that these are areas of huge unmet medical need. Often, there isnt a high standard of care with either medicines or clinical interventions that are ultimately influencing the progression and the symptoms of the disease, he says.

A lot of rare diseases often affect children by the very nature of their being of genetic origin. In some cases, children dont get the opportunity to grow up into adulthood because of these rare diseases. Having the opportunity to develop medicines where there is such a high level of unmet need and, ultimately, impact in a positive way the lives of families and their carers is a huge motivation.

Dr Winburn adds that rare diseases, collectively, are common. There are approximately 7,000 rare diseases, and the majority of these are of genetic origin. Gene therapy offers a groundbreaking technology to address these genetic diseases that have historically not had particularly strong standards of care or clinical treatment paradigms offered to them.

Gene therapy for haemophiliaPeople with the genetic disorder of haemophilia have insufficient levels of a clotting factor that helps to stop bleeding. Consequently, they bleed for longer than other people. The disease is typically treated through infusions of the missing clotting factor, with patients undergoing regular replacement therapy. Gene therapy could revolutionise this treatment model.

Its really important to put yourself in the position of a parent who has a young child who has haemophilia, Dr Winburn says.

Often, this disorder of coagulation that results in spontaneous bleeding due to the lack of functioning clotting factor first presents as early as the age of two, classically when children are becoming toddlers, when they start bumping into things and they develop bruising and the likes.

That alerts their parents attention to the possibility that there is something wrong with their clotting system and they [undergo] clinical tests and a diagnosis is made. Or, because its a genetic condition, it may run in families and parents are aware of the possibility of their newborn having haemophilia.

But if you are diagnosed, for example, at the age of two, it means that the mainstay of treatment is factor replacement. So, that commonly is an intravenous infusion possibly two to three times a week, possibly once a week, or once every other week, depending on whether its haemophilia A or B and what type of medicine is being prescribed. But its certainly frequent treatments. Again, if you put that back to a parent wholl be doing those infusions from the age of two or three that lifelong need and burden is huge.

While factor replacement enables children to live a full and active life to a degree, children with haemophilia may not necessarily get the opportunity to engage in all the activities children typically partake in as they are growing up, such as contact sports, Dr Winburn says.

There is this ongoing, lifelong burden of treatment. As those boys transition into adulthood, they often take responsibility for that and if they dont get their treatment then they will bleed spontaneously into their joints, they get problems with haemarthropathy, causing damage.

Ultimately, the incidence of joint damage and joint replacement surgeries is incredibly significant in the haemophilia population. And that is often despite optimal prophylaxis, where its being prescribed.

So, when you think about gene therapy, this is a single, one-off treatment with the potential to alleviate the need for regular infusion for a patient.

Not all patients will be eligible for a gene therapy or are being studied in gene therapy trials. This is not going to be something thats available for everybody. But for those that are eligible, and ultimately in disease where a gene therapy has been licensed by the regulator, this really does have the potential to massively impact their lives and give them a sense of normality that they havent necessarily had up until that point in time.

Future expectationsWhile gene therapy holds promise for many people with genetic diseases, it will not be an appropriate solution for every patient. The potential risks and benefits of gene therapy will be fully established through clinical trial programmes and with continued research and evaluation.

Patient safety and suitability are always primary considerations in the development of new treatments as they progress from preclinical and clinical testing through regulatory approval to potential commercial distribution. Dr Winburn stresses that, as regards the development of new gene therapies, patient safety is paramount.

Safety is always at the forefront of our thinking, it is the heart of our clinical trial programmes, it is the heart of all our regulatory work.

It is an ongoing process around evaluating safety, and particularly long-term safety, and there is a critical importance for all patients that ultimately receive a gene therapy to be followed up long-term within registries, within clinical databases, so that we can monitor and evaluate long-term safety. All our trials are designed so that safety outcomes are critically part of it and its something that we are ever watchful of.

For some patients, gene therapy is already a reality. There are currently a few rare diseases for which gene therapies are available as therapeutic options in Europe, and Dr Winburn anticipates that there may be up to 30 approved by 2023.

There is a rare congenital cause of blindness that currently has a gene therapy available and similarly a rare neurological condition that affects children also has a gene therapy available, thats spinal muscular atrophy (SMA). There is also a gene therapy for beta thalassaemia that has recently been approved and is available within Europe. In terms of haemophilia, the first gene therapy is currently under review in Europe.

It may be premature to imagine a scenario whereby gene therapy is used to treat chronic diseases more generally, but in terms of future applications for these emerging technologies it is a case of watch this space.

This is an area where we are definitely in breakthrough technology. At this moment in time, our focus has been on rare diseases. There is, of course, an interest in understanding what is possible with gene therapy in terms of where it could be utilised, Dr Winburn says.

I dont want to provide any false hopes, but I think aspirationally, there is a hope that this could certainly impact many patients and their families in a positive way.

In association with Pfizer Biopharmaceuticals Group.

Continued here:
Gene therapy: The 'next generation' of medicine - Irish Medical Times

Press Release

6 May 2020

Immunicum AB (publ) Receives Regenerative Medicine Advanced Therapy Designation from FDA for Ilixadencel in Kidney Cancer

Immunicum AB (publ; IMMU.ST) announced today that it has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA) for the Companys lead candidate, ilixadencel, a cell-based, off-the-shelf immune primer for the treatment of metastatic Renal Cell Carcinoma (mRCC). The FDAs decision was made based on the previously communicated results from the Phase II MERECA clinical trial that evaluated the safety and efficacy of ilixadencel in combination with Sutent (sunitinib) in patients with newly diagnosed mRCC. Advantages of the RMAT designation include all the benefits of the Fast Track and Breakthrough Therapy Designation programs including guidance and early interactions with the FDA to discuss potential surrogate or intermediate endpoints to support accelerated approval as well as potential ways to satisfy post-approval requirements.

We are very excited to have received the RMAT designation for ilixadencel in kidney cancer as it recognizes both the potential of our novel therapeutic approach as well as the clear need for viable therapies to address this difficult-to treat disease. As a designation similar to the FDAs Breakthrough Therapy Designation, we will now also have the opportunity to receive direct guidance from the FDA which will inform key development decisions and ultimately bring us closer to delivering ilixadencel to patients in need, commented Alex Karlsson-Parra, CEO of Immunicum.

Established in 2017 under the 21st Century Cures Act in the United States, RMAT designation is an expedited program designed to facilitate the development and review of regenerative medicine therapies intended to address an unmet medical need in patients with serious conditions. An investigational regenerative medicine therapy (e.g. cell or gene therapy) is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious condition and preliminary clinical evidence indicates that the drug or therapy has the potential to address unmet medical needs for such a disease or condition. As a cell therapy medicinal product, ilixadencel falls within the definition of a regenerative medicine therapy.

The latest results of the Phase II MERECA trial were presented in February at the ASCO-SITC Clinical Immuno-Oncology Symposium 2020 in Orlando, Florida. As of December 2019, the patient follow up data indicates a separation in Kaplan-Meier survival curves in favor of the ilixadencel treatment group in line with the projected separation based on the data from July 2019. The median OS value could not be calculated yet in either group as the data is not mature. The confirmed ORR for the ilixadencel treatment group was 42.2% (19/45) versus 24.0% (6/25) for the sunitinib control group.

Refer to the following link for more information on Regenerative Medicine Advanced Therapy Designation: https://bit.ly/3c7bFah

About MERECAMERECA is an exploratory, international, randomized, controlled and open-label Phase II clinical trial in which a total of 88 newly diagnosed, intermediate and poor-prognosis metastatic renal cancer patients were enrolled. Based on a 2-to-1 randomization, patients received either two intratumoral doses of ilixadencel before nephrectomy (surgical removal of the tumor-affected kidney) and subsequent treatment with sunitinib or sunitinib therapy alone post-nephrectomy. The primary objectives of the study are to evaluate median OS and 18-month survival rates. Secondary objectives include evaluation of safety and tolerability, tumor response and immunological profiling including T cell infiltration.

About renal cell cancer / carcinomaThere are approximately 273,000 new cases of Renal Cell Cancer diagnosed worldwide each year, representing approximately two percent of all cancers. The therapeutic effect of existing treatments, called targeted therapies, is often of short duration, with limited survival gain. With no alternatives to these therapies, there exists a relatively large unsatisfied medical need for new treatments that are effective, more cost-efficient and have less unwanted side effects.

About ilixadencelIlixadencel is an off-the-shelf cell-based cancer immunotherapy developed for the treatment of solid tumors. Its active ingredient is activated allogeneic dendritic cells, derived from healthy blood donors. Injection of these cells in the patients tumor generates an inflammatory response which in turns leads to tumor-specific activation of the patients cytotoxic T cells. To-date ilixadencel has been tested in a range of clinical trials in various solid tumor indications including metastatic Renal Cell Carcinoma (mRCC), hepatocellular carcinoma (HCC) and gastrointestinal stromal tumors (GIST) and in combination with several standard-of-care cancer therapies such as the tyrosine kinase inhibitors Sutent (sunitinib) and Stivarga (regorafenib), and the checkpoint inhibitor Keytruda (pembrolizumab). Ilixadencel has consistently maintained a positive safety and tolerability profile and demonstrated initial signs of efficacy as seen in the randomized Phase II MERECA trial. Ilixadencel is currently moving towards late-stage clinical development.

The information is such information that Immunicum is obliged to make public pursuant to EU Market Abuse Regulation. The information was released for public disclosure through the contact persons detailed below on 6 May 2020 at 8:00 am CET.

For more information, please contact:

Alex Karlsson-Parra, CSO and Interim CEO, ImmunicumTelephone: +46 8 732 8400E-mail: info@immunicum.com

Sijme Zeilemaker, COO, ImmunicumTelephone: +46 8 732 8400E-mail: info@immunicum.com

Continued here:
Immunicum AB (publ) Receives Regenerative Medicine Advanced Therapy Designation from FDA for Ilixadencel in Kidney Cancer - GlobeNewswire

Health care professionals can help adolescents prevent obesity from becoming an unwanted side effect of the unique growth period they undergo on their way to adulthood.

As a nurse, family nurse practitioner, and investigative researcher for the National Institutes of Health, Dr. Paule V. Joseph has worked extensively with individuals with diabetes and obesity. Here she talks about the rise of obesity in adolescents, the diabetes-related health implications, and what we can do to reduce young peoples risk for obesity.

Q: How critical is the issue of adolescent obesity?

A: Based on the current data, almost 21 percent (PDF, 588.88 KB) of adolescents ages 1219 are affected by obesity. The obesity rate among all populations has increased steadily, although there is some evidence, at least with childhood obesity, that its starting to level off. But theres a lot that needs to be done to decrease the amount of childhood and adolescent obesity.

Q: For adolescents, what risk does obesity pose for acquiring type 2 diabetes?

A: There's plenty of evidence that has linked obesity to type 2 diabetes. Teens and even younger children who have obesity are at a higher risk. They develop insulin sensitivity and you start to see changes in their hemoglobin A1C. When you see this, its important to intervene with nutrition information, because there might still be time to prevent type 2 from developing. This is very important, because the consequences of type 2 diabetes and the comorbidities associated with it are so detrimental to health.

Q: Is the prevalence of adolescent obesity the same across races and ethnicities?

A: Prevalence is highest among non-Hispanic black and Hispanic youth. This, of course, puts them at higher risk for comorbidities such as type 2 diabetes, cardiovascular disease, early cancer, and other disorders that have been associated with obesity.

Q: What is it about adolescents that makes them different from adults in terms of obesity risk?

A: We have all been adolescents, so we know about the changes that happen to our bodies during that time. Adolescents are growing, so they need more calories. However, its the source of those extra calories that can be the problem. We are seeing that consuming excess sugar and fat is putting adolescents at higher risk of developing obesity.

Besides the rapid growth that they are experiencing, adolescents are also undergoing changes in brain development. They are starting to make their own choices about whether to eat foods that are good or bad, and theyre experiencing a lot of peer pressure with those decisions. Theyre also experiencing hormonal changes that might give them stronger cravings for certain foods.

During adolescence, you would expect there to be increased physical activity, but in the era in which we are living, a lot of adolescents are actually quite sedentary. For example, many are spending a lot of time playing sedentary video games instead of being active.

These are all reasons why we need prevention efforts and new interventions that can decrease the risk for adolescent obesity. But one of the big gaps in the literature is studies focused on adolescents; a lot of obesity studies lump them together with younger children. Adolescents are not children and theyre not adultsthey are a unique group, and therefore, we should study them separately.

Q: What are some of the environmental factors affecting adolescent obesity?

A: Socioeconomic status is definitely one of the predictors of obesity. It's interesting because in the United States, we see that adolescents with lower socioeconomic status are more likely to develop obesity while if you look at adolescents in low-resource countries outside the United States, its the total oppositethe kids with higher socioeconomic status are more affected by obesity. That could be because in those low-resource countries, money may give access to fast foods. But here, sometimes its cheaper to buy fast foods compared to healthy foods.

Another environmental factor, which I alluded to earlier, is the influence of friends. Its like, My friend is drinking a soda. Why cant I drink one? Even when adolescents know they have diabetes and are not supposed to drink a soda, sometimes peer pressure affects them.

Having healthy foods available is another environmental factor. Some neighborhoods are food desertsthe availability and accessibility of healthy foods is limited. Also, if you go to the supermarket, all the tempting snacks are placed right at the checkout line. We are visual individuals, so even if youre not hungry, sometimes you just become hungry when you see these things. Furthermore, we have to look at the food being served in school cafeterias and vending machines.

Environmental factors create incentives and disincentives to get the physical activity that can help manage obesity. The American way of life is less set up for walkingsuch as to a school, for errands, or to get to a jobthan ever before. Urban planners are trying to create more walkable environments, but as a country were not there yet. Young people today also may get less physical activity if their environment does not provide them access to gyms, parks, playgrounds, and other safe places to move around, or if they cannot afford recreational activities or equipment.

And, of course, there are cultural differences. We have adolescents who are fourth and fifth generation Americans, but we also have those who have just arrived in the country. In groups new to the country, you can see changing trends in their eating habits as they adapt to this culture, which parallels trends in weight gain. This ties back to those pressures we just discussed.

Recently, there have been several studies on sleep. An adolescents chronotypetheir innate preferences for waking and sleepinginfluences not only their sleep patterns, but also the way their body processes foods. So, their sleep schedule, and how well it fits with their chronotype, may affect weight. Furthermore, an adolescents school and activity schedule may not provide time for physical activity and can cause stress, which is linked with obesity.

Q: What is known about genetic influences on obesity?

A: Several genes have been associated with higher risk for obesity. Genetic variables have been associated with body size, body mass index, waist circumference, appetite, and more.

We used to be taught that the genes that you were born with are the genes that you are stuck with. However, now we know that the environment influences the genome, creating epigenetic changes that affect obesity. Therefore, its very important to study the adolescent group separately from children or adults. We know that you are born with certain genes, but we also understand that the environment affects and interacts with our genes. So ultimately, it is the combination of our genes and our environment that determine our health. For example, eating healthy foods may reduce our genetic risk for disease.

Q: What further research do you think needs to be pursued on the topic of adolescents and obesity?

A: We need to learn more about applying precision medicine to obesity. How can we use zip code data, other data from patients medical records, gene sequencing, and so forth, to create a more personalized model of treatment? Preventing and treating obesity is not one-size-fits-all. We need more studies separating younger children from adolescents, so that we can really understand this unique population.

Q: What can health care professionals do to prevent and treat obesity in their adolescent patients?

A: It's very important to be aware of the evidence that is emerging about obesity, despite the gap between the research and application of this knowledge in clinical practice.

You can get families involved in various ways. For example, you can have nutrition talks while you're doing your physical assessmentstaking time to ask, What it is that youre eating? We clinicians do a lot of assessments, such as well-child checks, but we need to screen not only for obesity, but also for what they are eating. That way, we can actually intervene earlier before the adolescent develops type 2 diabetes.

Also, motivational interviewing can help. Provide examples of people who were on a weight-gain trajectory before and how they have taken control of their health. You also can provide visual examples, such as a model of fat, which is easily obtained on the Internet, to show your patients what it looks like and to say, This is being stored in your body. This can be influential in terms of a young patients decision making. Sometimes theyll say, I don't want that to happen to me.

As another example, a randomized control trial conducted by NIDDK researcher Dr. Kevin D. Hall studied the impact of eating unprocessed versus ultra-processed foods, and the published study results includes pictures of menus. I have clinician friends who have taken those pictures and put them up in their waiting rooms, so by the time patients go into an exam room, theyre already saying, I'm not supposed to have chips, because thats a processed food.

You can encourage your young patients to incorporate more physical activity into things they already like to do. If they like video games, for example, they can be encouraged to try active video games, or exergames. The National Institutes of Health has sponsored some promising research into the health benefits of this activity. As another idea, some teens may be motivated by competing with themselves or their friends on how many steps they can take in a day, using step-counting devices. This is an exciting area of current research.

I do think its important to know the population that youre taking care of, know what has worked, and try some of those things. For example, my colleagues and I wrote a paper, Adolescent Obesity in the Past Decade: A Systematic Review of Genetics and Determinants of Food Choice, that reviewed a total of 41 full-text articles that contained studies limited exclusively to adolescents. Its generated a lot of discussion and I encourage health care professionals to read it.

Editors Note: Health care professionals are encouraged to share with adolescent patients and their families these two resources:

More here:
Teens, Genes, and Food Choices: What Contributes to Adolescent Obesity? - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)