Join dozens ofStanford Medicine studentswho receive up to three years of funding and valuable leadership skills asKnight-Hennessy Scholars(KHS).

KHS admits up to 100 select applicants each year from across Stanfords seven graduate schools, and delivers engaging experiences that prepare them to be visionary, courageous, and collaborative leaders ready to address complex global challenges. As a scholar, you join a multidisciplinary and multicultural cohort, participate in up to three years of leadership programming, and receive full funding for up to three years of your graduate studies at Stanford.

Candidates of any country may apply. KHS applicants must have earned their first undergraduate degree within the last seven years, and must apply to both a Stanford graduate program and to KHS.

If you aspire to be a leader in your field, we invite you to apply. The KHS application deadline is October 12, 2022. Learn more aboutKHS admission.

Knight-Hennessy Scholars application deadline: 1:00pm pacific time, October 12, 2022

MS Human Genetics and Genetic Counseling application deadline: December 6, 2022

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Admissions | Master's Program in Human Genetics & Genetic Counseling ...

The Warren Alpert Foundation funding becomes the most significant award to support genetic counseling education nationwide

PHILADELPHIA Penn Medicine has been awarded a $9.5 million grant from the Warren Alpert Foundation to continue its efforts to increase diversity in genetic counseling, a field that, despite impressive leaps forward in genetic knowledge, lacks a diverse workforce. The Alliance to Increase Diversity in Genetic Counseling grant will support 40 underrepresented students in five genetic counseling programs in the Northeastern U.S. over five years to expand all dimensions of diversity. PI Kathleen Valverde, PhD, LCGC, the Director of the Master of Science in Genetic Counseling Program at the Perelman School of Medicine at the University of Pennsylvania, will lead this effort, joined by a consortium of participating Genetic Counseling masters programs from Boston University, Rutgers University, Sarah Lawrence College, and the University of Maryland School of Medicine. Ten students will be selected yearly, two from each program, to receive full tuition support and a cost of living stipend. Click here for more information on the Alliance to Increase Diversity Scholarships at the University of Pennsylvania.

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Masters Program in Genetic Counseling - Perelman School of Medicine at ...

Failed efforts do not overshadow fields progress, resolve.

The recent news of Biogen and Ionis Pharmaceuticals ending a clinical trial for their amyotrophic lateral sclerosis drug candidate and Roches failed Phase III study in Huntingtons disease (HD) are hard to bear for many families holding on to hope in the face of devastating diseases with limited options. Their drug development journeys underscore the highly challenging nature of tackling rare diseases. As a geneticist, Ive seen firsthand the difficulties these patients endure. But even in the face of what might seem like failure, there is great progress. New thinking, research, and discoveries are only made possible by those who bravely forge new paths to gain a better understanding of the human body, even when that risk entails failure. Success will come.

The silver lining? Our strategy is sound. There is no doubt that genetic medicines work at addressing root causality in monogenic rare diseases like HD.

Back in the mid-1980s, a group of scientists came together at Alta Ski Resort to investigate whether it was possible to detect increased mutations in the survivors of the Hiroshima and Nagasaki bombings. The conclusion was that current methods were insufficient, yet the meeting spurred an energized response around genetic sequencing that resulted in the federal government funding the multibillion-dollar, multinational, and multiyear project to sequence all six billion letters of the diploid human genome, which resulted in the publication of the draft sequence of the human genome in 2001, years earlier than expected.

In less than four decades since, we have unraveled the blueprint of human life, cataloged the vast majority of mutations in the genetic code, implemented global infrastructure to provide rapid and inexpensive genetic testing to patients and physicians, and have a first wave of genetic medicines saving human lives. This is breathtaking progress.

However, there is still much work to do, with numerous challenges centered on improving the delivery, selectivity, and tolerability of these genetic medicines. We know the medicines work; it is just a matter of getting the therapy to the tissue where the disease manifests, dialing in the selectivity for the gene of interest, and engineering out toxicities.

With HD, patients receive an injection into the spinal cord, but in order for enough of a relatively large genetic medicine to penetrate into the deep brain structures to be effective, the high concentrations of the drug injected at the surface of the brain may result in neurotoxicity.

Rapid advancements in the areas of delivery, selectivity, and tolerability are happening. For delivery, innovations are allowing us to deliver genetic medicines across the blood-brain barrier to allow uniform exposures across all brain regions and not setting up toxic gradientswhich has been difficult for large molecules. This method avoids the brain surface toxicity. Since HD is a disease that involves the whole body, delivering a solution systemically via the bloodstream may address the whole-body manifestations of the disease. These new delivery devices are also noninvasive, using either ultrasound or emerging tech, and allow effective administration in a previously impossible manner.

For selectivity, emerging technologies can identify and engage with only the targeted mutated gene. Weve essentially reverse engineered nature so that the genetic-medicine-to-gene-target interface wont tolerate any mismatches. The treatment is viewed by the body as a complementary sequence to the mutant gene, yet one that contains a biologically inert chemistry that ensures no off-target engagement. The end result will be clean, highly effective, and well-tolerated medicines.

Because many of these therapies are delivered systemically, they can trigger an immune reaction that renders the medicine intolerable, yet even on this front, we are seeing advancements. By using the bodys own intelligent design, scientists have copied the existing framework and then improved upon it using synthetic strategies that allow for greater tolerance, thereby preventing the normally useful immune response from derailing healing.

We are in the most exciting time in the history of medicine, bar none. The science is dazzling. Patients should feel very optimistic. Cures are coming not in decades, but in a matter of years. The innovation thats happening today will be the breakthrough therapies of tomorrow. If you are looking for a silver lining, here it is.

Dietrich Stephan, CEO, Chairman, and Founder, NeuBase Therapeutics

See the article here:
The Silver Lining Of Innovation in Genetic Medicine - Pharmaceutical Executive

Asher Gerlach, age 6, is a special kid. Not only because hes one of just 2030 children in the world with an exceptionally rare genetic disease, according to medical literature, but also because he has a refreshing take on life.

Asher is super-affectionate. He snuggles with everyone, says his mom, Jen Gerlach. He cant say snuggle, so he says guggle instead. And please comes out as leese. So when he wants a hug, he says, Guggle leese? And hes hilarious. Hes always making us laugh.

Asher lives with his mom and two siblings, Isaac, age 8, and Shiloh, age 3, in San Jose, California. They enjoy being outdoors, swimming, and riding bikes together. One of their favorite family activities is building Brio trains and setting up train tracks, which often travel down the stairs and all around the houseinspired by their beloved late father, Josh, a structural engineer.

Jen is the most wonderful mother and advocate for Asher. Shes extremely well educated about his genetic condition, and shes motivated to learn as much as possible so she can help Asher and teach others, says Jenny Kim, MS, LCGC, a genetic counselor at Stanford Medicine Childrens Health.

Ashers genetic condition is Yuan-Harel-Lupski (YUHAL) syndrome. Its associated with neurological symptoms, physical differences, and developmental delays.

Its a rarely seen chromosome abnormality, which involves the short arm of chromosome #17. Its a duplication of this region that includes a couple of important genes, says Melanie Manning, MD, a medical geneticist.

Making the hard decision to proceed with genetic testing for Asher

At first, Gerlach balked at the idea of genetic testing for Asher. As a high school science teacher, she helped with the Human Genome Project, and she doubted the ability to accurately pinpoint errant genes. Yet after receiving the recommendation from different caregivers, she acquiesced. Shes extremely glad that she did.

Its terrifying for parents to take that hard step with genetic testing, but it gave me so much. It gave me the ability to talk intelligently about what is happening with my child, Gerlach says. And it gave me access to services. Before, I fought tooth and nail for services. Today, Im empowered to help Asher, and I have the tools I need to take care of him.

Stanford Medicine Childrens Health Genetics Services include consultation with geneticists and genetic counselors. They specialize in providing and coordinating comprehensive care for children and adults with suspected or confirmed genetic conditions.

Genetics has been my go-to contact. There have been many times on my journey where I knew that I needed help with a particular issue that Asher and I were facing, but I didnt know which specialty to talk to about the issue, Gerlach says. The genetics team is so informed and incredibly helpful with problem-solving.

To diagnose Ashers genetic condition, the team ran a chromosomal microarray, which can detect extra or missing pieces of genetic information. Genetic information contained on the chromosomes is in a delicate balance, and any extra or missing information may cause differences in health, development, and growth.

Knowing their childs genetic makeup is helpful for families. It helps them understand what to expect for the future, Dr. Manning says.

When families read the report of genetic findings for the first time, they can feel overwhelmed. The genetics team breaks it down in terms that are easy to digest and highlights whats important.

Finding out that he had YUHAL syndrome was horribly hard but empowering, Gerlach says. As a scientist, I joke that if you are going to have something, it might as well be cool and super-rare, but as a parent its terrifying.

The genetics team created a personalized care plan for Asher for the coming years. They also stay on top of new, relevant information related to his genetic condition.

Having genetic testing opens up options for families, Kim says. For Ashers family, we set them up with specialists, connected them with other families of kids with rare genetic disorders, and helped them get involved in YUHAL syndrome research.

Asher qualifies for special education because of his multiple disabilities. Despite his challenges, hes a high achiever without any behavioral problems.

Hes the only full-inclusion special needs child in his kindergarten class, which means he participates in all subjects with the help of a one-on-one aide, Gerlach says.

She describes Asher as a contented child who loves to laugh and goof around. The other day when she asked what he wanted for dinner, he said, First Ill eat chocolate, then a cupcake, and then noodles! Special treat first, Mama!

Genetics as a gateway to personalized, multidisciplinary care

Genetics partners with a wide range of specialties and subspecialties at Stanford Medicine Childrens Health to provide personalized, multidisciplinary care for Asher. Theres power in having all providers on the same page, especially for kids with highly complex medical and developmental needs.

Because we are so connected throughout the world, and we have world leaders in different conditions, we are able to provide care for children with these extremely rare disorders, says Miguel Moreno, MD, Ashers neurologist. Other childrens hospitals across the nation often refer children with rare diseases to us.

Asher receives care from 16 specialty programs at Stanford Medicine Childrens Health: general pediatrics; genetics; ear, nose, and throat; neurology; neuromuscular; pulmonology; cardiology; nephrology; urology; ophthalmology; plastic surgery; developmental-behavioral; audiology; orthopedics; physical therapy; and occupational therapy.

Recently, Asher was having obstructive airway issues and difficulty breathing. He needed to be evaluated under anesthesia by an ear, nose, and throat (ENT) specialist to find out why.

This was one of eight procedures that he needed, so I asked if there was any way they could do everything at once during his ENT surgery, and they did it. They coordinated it all, Gerlach says.

Douglas Sidell, MD, FACS, took charge in coordinating the day, which included a sleep-state endoscopy, laryngoscopy, tonsillectomy, sedated echocardiogram, blood draw, and more.

This level of coordination is really quite common. We try to do everything at once for all children, but this becomes particularly important in children with multiple complex needs. It saved Asher additional anesthesia, and it saved Jen from having to run back and forth to eight separate appointments and time away from work, Dr. Sidell says. It reflects on the exceptional communication we have among providers, which is part of our culture.

Getting neurological care for hypotonia and developmental delays

A main player on Ashers extensive care team is neurology. When Dr. Moreno first met Asher, he suspected a genetic disorder.

Ashers constellation of findingsfrom his extra digits, urinary issues, developmental delays, and autism featuresall pointed to a possible genetic condition, he says.

Earlier on, Gerlach worried that Asher might have seizures, so Dr. Moreno ran tests, including an EEG brainwave, which can detect abnormal activity associated with seizures. Ashers testing did not reveal seizure activity, and he did not have signs of cerebral palsy, but he was diagnosed with hypotonia (low muscle tone).

We are watching Ashers hypotonia, and we are providing extra support as he needs it, such as bracing and special orthotics so he can have confidence with walking, Dr. Moreno says. We are also keeping an eye out for peripheral nerve damage, but hes currently doing pretty well. He has good strength, and he isnt experiencing tremors or shaking.

Asher receives regular care at the Pediatric Neuromuscular Diseases Clinic, led by John Day, MD, PhD, which combines innovative research with individualized care for children with neuromuscular diseases. Hes also receiving physical therapy, occupational therapy, and speech-language therapy on a regular basis.

Asher is full of energy, and he has a great personality. Hes very feisty, Dr. Moreno says.

The right place to care for children with multiple needs

Gerlach chose Stanford Medicine Childrens Health because, she says, it is a mecca for everything. She appreciates how Ashers many doctors and caregivers work together so intricately and how the hospital specializes in rare diseases. She says she has not had a bad experience at Stanford Medicine Childrens Health, despite coming here hundreds of times.

The care has been stellar, so why would I go anywhere else? They treat Asher like a human, not a specimen, despite his super-rare disorder, Gerlach says. I always feel affirmed as a parent.

Its a two-way street caring for children with extremely rare genetic disorders. Parents, like Gerlach, play a role in moving knowledge forward.

Its been incredibly valuable to learn from Jen, especially about this extremely rare disease, says Natalie Dykzeul, MS, LCGC, a Stanford Medicine Childrens Health genetic counselor also working with the Gerlachs. You can tell that she and Asher have a special, unique bond.

Gerlach soaks in every moment with Asher, appreciating him as the complex, beautiful child that he is, all while watching him for signs of health problems. Its simply the journey that we are on, she concludes.

Learn more about Genetics Services at Stanford Medicine Childrens Health >

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Genetics Team Serves as Go-to for Mom of Son With Extremely Rare Disorder - Stanford Medicine Children's Health Blog - Stanford Children's Health

A new study on Alzheimer's disease ties the brain's immune response to the condition, while scientists have identified a better antibody treatment for cancer and possible cell toxicity in CRISPR-Cas9 gene editing.

For that and more, continue reading.

New Insights into Predisposition for Alzheimer's Disease

Researchers withThe Mount Sinai Hospital/Mount Sinai School of Medicine, working with fresh human brain tissue harvested by way of biopsies or autopsies from 150 donors,identified21 genes that could elevate the risk Alzheimer's disease.

In particular, they point to SPI1, a possible key regulator of microglia, immune cells in the brain. Microglia are primarily responsible for the brain's immune response but play an important role in the development and maintenance of neurons.

This is not the first study to target microglia as playing a vital role in the genetic risk and development of Alzheimer's disease because of their involvement in maintaining brain cells and battling inflammation, both issues with Alzheimer's disease. The research waspublishedinNature Genetics.

"Our study is the largest human fresh-tissue microglia analysis to date of genetic risk factors that might predispose someone to Alzheimer's disease," senior author Panos Roussos, M.D., Ph.D., professor of psychiatry and genetic and genomic sciences at the Icahn School of Medicine at Mount Sinai and director of the Center for Disease Neurogenomics, said.

"By better understanding the molecular and genetic mechanisms involved in microglia function, we're in a much better position to unravel the regulatory landscape that controls that function and contributes to AD," Roussos added. That knowledge, he said, could pave the way for novel therapeutic interventions for AD.

Microglia are notoriously difficult to isolate and examine, but they managed to cull 150 high-quality microglia. They then compared epigenetic, gene expression, and genetic information from the samples in both Alzheimer's and healthy aged patients. In addition to expanding on previous DNA regulatory sequence data and genes whose dysregulation directly contributes to Alzheimer's, they described the cell-wide regulatory mechanisms that may help identify genetic regions implicated in specific aspects of microglial activity.

A New, Broader, Cheaper and Faster Checkpoint Inhibitor

Scientists atTel Aviv Universityand theUniversity of Lisbonhaveidentifiedand synthesized a small molecule they believe can be a better antibody to treat a variety of cancers. As is well known, T cells express a protein called PD-1 that disables their activity when it binds to the PD-L1 protein expressed in cancer cells, essentially allowing cancer cells to shut down the immune response against them.

This led to the development of checkpoint inhibitors, antibodies that block either PD-1 or PD-L1, allowing the T cells to attack the cancer cells. However, these antibodies are expensive and have been difficult to develop for solid tumors they're quite effective in blood cancers. Using bioinformatic and data analysis tools, the researchers identified a smaller molecule that appears to control tumor growth and the other antibodies by inhibiting PD-1/PD-L1 binding. It is biological rather than synthetic and is much simpler and inexpensive to create. They also think it should be able to be taken orally instead of intravenously.

What are Cell Antennae?

Almost every cell type in the human body has a rod-like projection called cilia. Researchers fromOhio State Universitylookedat cilia on neurons in the brain in a mouse model of a neurological disorder called Bardet-Biedl syndrome.

They were looking at dopamine receptor 1, one of five proteins that regulate dopamine signaling. In some parts of the brain, this receptor switches on motivated behavior. But their research found that if the receptor gets stuck on cilia or isn't given an opportunity to localize to the cilia, messages telling the body to move are decreased.

Dopamine receptor 1 appears to require getting to and from neuronal cilia for proper signaling. Bardet-Biedl syndrome is in a class of diseases called ciliopathies, where dysfunctional cilia on a range of cell types can cause multiple organ system defects, blindness, obesity and intellectual disabilities. In the mouse model, deletion of these Bardet-Biedl syndrome proteins hindered the movement of certain receptors to and from primary cilia.

CRISPR-Cas9 Gene Editing can Cause Cell Toxicity and Genome Instability

Researchers atIRB Barcelonahavereportedthat if gene editing occurs at certain spots of the human genome, it can cause cell toxicity and genomic instability.

CRISPR-Cas9 is a type of very precise gene editing, and since the beginning, there have been concerns over off-target edits. The effect is mediated by the linchpin tumor suppressor protein p53 and depends upon the DNA sequence near the editing point and various epigenetic factors in the surrounding location. The researchers analyzed the most popular CRISPR library designed for human cells and identified 3,300 targeted spots demonstrating strong toxic effects. They also reported that about 15% of human genes contain at least one toxic editing point.

Future-Proof COVID-19 Treatments?

A study by theUniversity of Kentin the U.K. andGoethe-Universityin Germany have found new therapies for COVID-19 that may offer better protection against future variants and outbreaks.

They tested the sensitivity of various SARS-CoV-2 Omicron and Delta viruses to combinations of four approved antiviral drugs with betaferon, another class of antiviral drug naturally produced in the body. They found that these new combinations were, at least in cell culture assays, highly effective. The addition of the interferon with molnupiravir (Merck's Lagevrio), nirmatrelvir (one of the antivirals in Pfizer's Paxlovid) and aprotinin (Bayer's Trasylol) was much more effective than interferon combinations with remdesivir (Gilead's Veklury).

"These are exciting findings that will hopefully help to improve the treatment of vulnerable COVID-19 patients and to avoid the formation of resistant viruses as much as possible," Martin Michaelis, Ph.D., the University of Kent, stated.

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Research Roundup: 21 Genes Linked to Increased Risk of Alzheimer's and More - BioSpace

A University of Iowa professor has received a grant for a project that looks at how scores measuring genetic influence on behaviors areutilized.

Anya Prince, a professor of law and faculty member of the UI Genetics Cluster Initiative, was awarded a four-year grantit totals $2.7 million, with more than $485,000 awarded to the UIfrom the National Human Genome Research Institute at the National Institutes of Health. The co-principal investigator is Jean Cadigan, associate professor of social medicine at the University of North Carolina, ChapelHill.

The project will focus on the increasing development of sociogenomic polygenic scores (PGS) that may predict complex behaviors and traits. The development of these scores has the promise to improve genetic and social science research, but it can also exacerbate social inequities and disparities if not implemented carefully. Prince, Cadigan, and a research team from across the country will examine how the scores are being utilized and ascertain the ethical, legal, and social effects of theiruse.

With an exploration of diverse viewpoints on the potential harms and benefits of sociogenomic PGS and assessment of the legal protections and barriers for implementation, this project seeks to better understand the ethical and social impacts of this new technology, Princesays.

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UI professor receives grant from National Institutes of Health - Iowa Now

Since the medicine's first approval in 2016, nearly 130,000 people in the U.S. have been treated with Taltz

INDIANAPOLIS, Aug. 8, 2022 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) announced today the availability of a new, citrate-free formulation of Taltz (ixekizumab) injection 80 mg/mL. The new formulation, which was recently approved by The U.S. Food and Drug Administration in May 2022, includes the same active ingredient as the original formulation. The new Taltz formulation significantly reduced injection site pain experienced by some people immediately following injection as shown by an 86% decrease in a visual analog scale (VAS) of pain versus the original formulation. Taltz is approved to treat adults and children six years and older with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, adults with active psoriatic arthritis, active ankylosing spondylitis (AS) and active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation.

"Taltz has long delivered effective treatment with a well-established safety profile that addresses symptoms for people living with plaque psoriasis, psoriatic arthritis, AS and nr-axSpA," said Ashley Diaz-Granados, vice president, U.S. Immunology at Lilly. "We're proud of our investment in research that keeps the patient experience at the center. This new formulation provides yet another reason to choose Taltz, and we look forward to introducing it to patients who have not yet tried Taltz and providing a seamless transition for those already enjoying the medicine's benefits."

Taltz citrate-free demonstrated a safety profile consistent with the original formulation. The safety information for Taltz can be found below.

Existing Taltz patients will not need a new prescription, nor should they experience a gap in their therapy. The new formulation is currently being shipped across the U.S. with anticipated broad availability for both new and existing Taltz patients by the end of the month. In the interim, the original formulation of Taltz continues to be available until it is replaced by the citrate-free formulation. The citrate-free formulation of Taltz was approved by the European Medicines Agency in December 2021 with several markets launching now and many more anticipated in the coming months.

"Today is an exciting milestone for the nearly 30 million people around the world who live with the challenging symptoms of these autoimmune diseases that affect the skin and joints," said April Armstrong, M.D., MPH, professor of dermatology and associate dean of clinical research, Keck School of Medicine at the University of Southern California. "In my six years of prescribing Taltz, I've seen firsthand the significant impact Taltz has had for patients across multiple indications. The availability of Taltz as a citrate-free formulation represents an important advance in patient care that will allow more patients to experience less injection-site pain."

Lilly is committed to improving experiences for people treated with Taltz, providing the same active ingredient in a new citrate-free formulation. Lilly's investment into patient-centric research is evident as Taltz has been studied in more than 10,000 people in clinical trials globally and has been available in most markets for more than five years.1 In the U.S., more people living with psoriasis are treated with Taltz compared to any other IL-17A antagonist, adding to the nearly 130,000 people in the U.S. who have been treated with the medicine.2

To learn more about real success stories with Taltz, please visit Taltz.com.

IMPORTANT SAFETY INFORMATION FOR TALTZ

CONTRAINDICATIONSTaltz is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients.

WARNINGS AND PRECAUTIONSInfectionsTaltz may increase the risk of infection. In clinical trials of adult patients with plaque psoriasis, the Taltz group had a higher rate of infections than the placebo group (27% vs 23%). A similar increase in risk of infection was seen in placebo-controlled trials of adult patients with psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, and pediatric patients with plaque psoriasis. Serious infections have occurred. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue Taltz until the infection resolves.

Pre-Treatment Evaluation for TuberculosisEvaluate patients for tuberculosis (TB) infection prior to initiating treatment with Taltz. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Taltz. Closely monitor patients receiving Taltz for signs and symptoms of active TB during and after treatment.

HypersensitivitySerious hypersensitivity reactions, including angioedema and urticaria (each 0.1%), occurred in the Taltz group in clinical trials. Anaphylaxis, including cases leading to hospitalization, has been reported in post-marketing use with Taltz. If a serious hypersensitivity reaction occurs, discontinue Taltz immediately and initiate appropriate therapy.

Inflammatory Bowel DiseasePatients treated with Taltz may be at an increased risk of inflammatory bowel disease. In clinical trials, Crohn's disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the Taltz group than the placebo group.During Taltz treatment, monitor patients for onset or exacerbations of inflammatory bowel disease and if IBD occurs, discontinue Taltz and initiate appropriate medical management.

ImmunizationsPrior to initiating therapy with Taltz, consider completion of all age-appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with Taltz.

ADVERSE REACTIONSMost common adverse reactions (1%) associated with Taltz treatment are injection site reactions, upper respiratory tract infections, nausea, and tinea infections. Overall, the safety profiles observed in adult patients with psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, and pediatric patients with plaque psoriasis were consistent with the safety profile in adult patients with plaque psoriasis, with the exception of influenza and conjunctivitis in psoriatic arthritis and conjunctivitis, influenza, and urticaria in pediatric psoriasis.

Please see fullPrescribing InformationandMedication Guidefor Taltz. SeeInstructions for Useincluded with the device.

IX HCP ISI 07MAY2020

About TaltzTaltz(ixekizumab) is a monoclonal antibody that selectively binds with interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor.IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Taltz inhibits the release of pro-inflammatory cytokines and chemokines.

About the Citrate-Free Injection Pain StudyThe citrate-free injection pain study (N=70) was a subject-blind, randomized, crossover study in healthy participants ages 18-75 years to determine injection site pain differences between Taltz citrate-free formulation compared to the original formulation of Taltz. The primary endpoint, pain intensity on injection, was measured by the Visual Analog Scale (VAS) of pain 0-100mm.3

About LillyLilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 47million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer's disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visitLilly.comandLilly.com/newsroomor follow us onFacebook, Instagram, Twitterand LinkedIn.

P-LLY

Cautionary Statement Regarding Forward-Looking StatementsThis press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Taltz as a treatment for people with moderate to severe plaque psoriasis, active psoriatic arthritis, active ankylosing spondylitis and active non-radiographic axial spondyloarthritis and other conditions and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that future study results will be consistent with study results to date. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

PP-IX-US-5653 08/2022 Lilly USA, LLC 2022. All rights reserved.

Taltz is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.

SOURCE Eli Lilly and Company

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Lilly's Taltz (ixekizumab) Now Available in New, Citrate-Free Formulation to Reduce Injection Site Pain for Improved Patient Experience - PR Newswire

Imagine a patient with a rare genetic disorder that makes their arms and legs have imprecise and slow movements. For years, the patient has faced serious restrictions in day-to-day life. They tried several treatments, but all have failed to ease the symptoms.

Now imagine a university team discovering a therapy that could tackle this condition, with a solution that lies in the patients own body. The patients blood would be collected, some key cells would be separated in a laboratory, gene-editing techniques would be applied, and personalised medicine, produced with specialised equipment, would be injected back into the patients body.

A biological process would then be triggered in which all faulty genes would be corrected, reducing the diseases severity, perhaps correcting it all together. The modification would be restricted to the patient and would not be passed on to their children, since it would not affect reproductive cells.

Our story has a catch, though: the blood cells needed for the personalised medicine are very fragile and do not live very long outside the human body. This means theres little time to take the blood to the specialised laboratory, transport the cells to the production facility, and take the medicine back to the hospital where the patient is.

But what if all these production steps were quickly performed in the same place that is, in the hospital?

Read more: The human body has 37 trillion cells. If we can work out what they all do, the results could revolutionise healthcare

Our story is ceasing to be just imagination because this way of producing medicines in the hospital is actually emerging. Its what specialists call point-of-care manufacture. And there are several notable examples of it already in use.

For instance, a medicine for multiple myeloma (a type of bone marrow cancer) is being produced in the Hospital Clinic in Barcelona, Spain. Products for severe burns are being manufactured in Lausanne University Hospital in Switzerland.

At the University of Colorado in the US, researchers are developing a therapy for hard-to-treat lymphoma, a type of blood cancer. In the UK, an NHS Blood and Transplant laboratory is investigating the manufacture of red blood cells which, if successful, could be carried out in hospitals and other clinical settings for the treatment of cardiac diseases.

These illnesses might not have been treated if the medicines had needed to be frozen and transported over long distances, instead of being made in the hospital.

Given that these therapies have such a short shelf life and will need to be produced at the patients bedside, there are many things we need to consider before we can deploy them on a wider scale. For example, what measures should hospitals, companies, and regulators take to adopt this model and make it work? This is what our research team has been investigating.

Its vital that the same safe and high-quality production methods are used in different hospitals so that all patients receive the best possible care. This is why regulatory agencies in the UK are already proposing new ways of managing this model.

For example, it has been suggested that to begin with, manufacturers could oversee the medicines production in several different hospitals from a central site. They could also be responsible for providing training and quality control in the hospitals that have rolled out point-of-care manufacture to ensure that the products are safe and high-quality.

But just because a new policy has been made, doesnt mean it will be successfully implemented. This will mean hospitals and companies will need to change how they operate for these new technologies to be implemented safely and efficiently.

Our research, in collaboration with the Medicines and Healthcare Products Regulatory Agency (MHRA) and several public and private sector organisations has also looked at what benefits and challenges there may be in implementing this innovative approach to the production of medicines.

In a recent publication, we put forward several steps that need to be taken by regulators, hospital staff, and companies to make the production of personalised therapies in hospitals a reality. First, trusts, clinical centres and hospital staff will need to investigate how best to make therapy production happen in medical wards. They will also need to identify any issues such as staff training and data management which may stop this from happening.

Companies already developing these advanced treatments can also supply hospitals with manufacturing equipment and production system know-how, making it easier to start developing personalised therapies in hospitals with as little disruption to day-to-day operations as possible. Regulators may need to provide guidance for different therapies to ensure quality control and patient safety.

Now, let us return to our patients story. After receiving the therapy produced in the hospital, the patient goes on to live a healthy life and have a child that is diagnosed with the same genetic condition. But now, the way to receive treatment is much clearer.

The child will be treated in a specialised hospital where certified equipment and trained staff are available for producing and delivering an enhanced version of the personalised therapy. With more experience and better infrastructure in place, the child will receive a treatment that yields faster outcomes with fewer side effects.

But this will only be possible if everyone including hospital staff, manufacturers, scientists and policymakers work together to ensure point-of-care manufacture is successfully rolled out.

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Personalised medicine made in hospitals can revolutionise the way diseases are treated the challenge now will be implementing it - The Conversation...

Antiviral drugs like remdesivir, molnupiravir and Paxlovid have undoubtedly saved lives and reduced the suffering wrought by covid-19 since they began rolling out in fall of 2020.

But theyre far from perfect, as President Joe Bidens recent experience shows. After treatment with Paxlovid, his covid infection rebounded, though his symptoms were mild.

With the pandemic showing no signs of slowing, the hunt for the next generation of covid treatments is speeding up. Pfizer and Merck the makers of Paxlovid and molnupiravir, respectively already have potential drug candidates that work better, or are easier to take, in their development pipelines. And many smaller biotech companies are also entering the race. They include Enanta Pharmaceuticals, which earlier this month reported a successful Phase I clinical trial of its experimental covid drug. Meanwhile, the Biden administration said in June that it planned to spend more than $3 billion to accelerate the search for better covid antiviral drugs.

I think the technical word to describe [the current covid] drugs would be suboptimal, said Luis Schang, a virologist at Cornell University. The drugs, all of which stem from antivirals developed before SARS-CoV-2 existed, have been a first good stab at beating back the virus in the body, he said, but they all have limitations.

But in the history of antiviral drugs, less-than-perfect initial stabs are the norm, experts said, drawing parallels with efforts to develop effective treatments for conditions like HIV and hepatitis C.

The first drug that we used against HIV, to be quite honest, was miserable, Schang said. AZT, first approved in 1987, caused serious side effects, and its effectiveness wore off quickly sometimes in just days as the virus evolved resistance. It took nearly a decade of research for scientists to develop a breakthrough triple-drug therapy in 1996 that combined several antiviral drugs to combat resistance. But the regimes involved complicated dosing and serious side effects that hampered their use. Now, there are more than 30 antiviral drugs for HIV, and its possible to treat the condition with just one pill a day.

Those first-generation drugs were better than nothing, but it took years of research to find better options. As the second-, third- and fourth-generation drugs were developed, the drugs got more potent, had less side effects and can be given less often, said Sara Cherry, an immunologist at the Perelman School of Medicine at the University of Pennsylvania. It really speaks to the fact that every development of a new drug can help mitigate all the things about the first generation that were imperfect.

From the earliest days of the pandemic, researchers and pharmaceutical companies have suspected that the first covid drugs to market wouldnt end up being the final word on treating the disease.

When clinical trial data showed remdesivir to be the first effective coronavirus drug, Anthony Fauci, Bidens medical adviser and leader of the National Institute of Allergy and Infectious Disease since 1984, cautioned that this was just the beginning, reflecting on his involvement in early HIV drug research. That was not the end game, because building on that every year after we did better and better, we had better drugs of the same type, and we had drugs against different targets, Fauci said.

The second-generation covid antivirals closest to approval will likely target similar aspects of the coronavirus as existing drugs, but better. Pfizer is reportedly working on an improved version of Paxlovid that would make it less problematic for people taking other medications, and the Japanese company Shionogi developed a once-a-day drug that works similarly to Paxlovid (which must be taken multiple times a day), that could be approved within months. An infusion of research money into a long-neglected field is fueling experimentation, with many labs developing new ways of stopping SARS-CoV-2, some of which might work against many other viruses.

In the future, I think that were going to have more drugs against similar targets, were going to have drugs against new targets. And hopefully, well have combinations in the future that will really slam the virus, Cherry said.

Viruses are little more than tangled strands of genetic material (RNA, in SARS-CoV-2s case) enclosed in a protein shell. They dont have the ability to reproduce on their own and instead hijack the machinery of their hosts to copy themselves.

Antiviral drugs are designed to gum up this process. Viruses that arent reproducing dont cause acute disease, typically, said Jeffrey Glenn, a gastroenterologist and molecular virologist at Stanford University. So, we want to interfere with their ability to reproduce themselves.

Most existing antiviral drugs, for any disease, aim to disrupt something about the virus itself. Many target viral polymerases, the proteins viruses use to make copies of their genetic material once they infect a host. Remdesivir, for instance, mimics the coronavirus genetic material, halting replication. Another common target is viral proteases, enzymes a virus needs to make proteins that make more viruses. The active ingredient in Paxlovid, which consists of two medications, inhibits a key enzyme needed to produce this replication machinery. The other ingredient slows the bodys metabolism of the active ingredient, helping it work longer.

In cell culture, these all work quite well to block viral infection, said Cherry. But when you move into an organism, theres a lot more complications, she said. Our bodies might break down a drug too quickly for it to clear enough virus, or the drug may not reach peak concentration in the lung or respiratory tract, where viral replication is happening. With potentially billions of viral particles to counter, getting this concentration right really matters, Cherry said, and can take time to perfect.

Imperfect single antivirals can also foster the evolution of drug-resistant strains of a virus. By knocking down susceptible strains in an infected individual, the antiviral can give resistant strains a leg up, allowing them to flourish within that individual and spread. The single drugs initially used for HIV evolved resistance generally quickly, said Matthew Frieman, a coronavirus researcher at the University of Maryland. It wasnt until they started combining two and three and four drugs together, these drug cocktails, that scientists learned this worked much more efficiently.

Combining multiple antiviral drugs makes it much harder for a virus to evolve resistance, since its being hit from many different angles at different stages of the replication cycle, Frieman said. The strategy is often simply more effective, too. By hitting it at multiple steps in life cycle, you can really enhance the effects of any one of these drugs individually, he said. You can also generally use less of each drug, which can reduce side effects.

Identifying drugs that might work together is one crucial step, and scientists have already begun testing different combinations in the lab. The other part is combining together drugs developed by different companies, Frieman said. It becomes an issue of money and patent rights, which can be difficult. Altogether, the process of developing combination therapy can take many years, he said.

There are currently no trials underway testing Paxlovid with other drugs, and some experts worry that combining molnupiravir, which works by introducing mutations into SARS-CoV-2s genetic material, could breed resistant strains. Consequently, more antiviral drugs may need to get developed before combination therapies come online. Thankfully, scientists are looking for new targets at an unprecedented scale in antiviral research.

Most antiviral drugs, for any condition, target two key factors of viral replication, polymerases and proteases. I expect the next generation [of covid antivirals] will come from optimized protease and polymerase inhibitors, said Schang. Some versions, which are easier to take and have fewer drug interactions, might be approved within months. But many scientists are starting to think beyond these targets.

Antiviral therapies are heavily biased toward protease inhibitors and polymerase inhibitors, said Schang, and thats resulted in a relative scarcity of chemical scaffolds that are known to have antiviral activity. Thats a major limitation moving forward. We have to have more chemical diversity.

There are many ways to throw a wrench in viral replication. For example, before a virus can replicate, its viral RNA must be unwound by enzymes called helicases. There are lots of programs trying to develop helicase inhibitors against SARS-CoV-2, Cherry said. Other scientists are working on ways of creating chinks into the coronavirus armor, designing antivirals that blow apart the protein shell that encases viral genetic material.

Other researchers are trying to design drugs that deprive viruses the opportunity to usurp our cells, by latching onto parts of human cells that the virus hijacks to invade or blocking access to human cellular components the virus needs to reproduce.

The approach is relatively new, and few drugs use it, but so-called host-directed antivirals could have advantages, said Glenn of Stanford. Since youre targeting something not under the virus control, we predict a high barrier to development of resistance, he said. Such drugs might work against other viruses too. If one virus has evolved to depend on a certain host function, its likely others have too, he said.

Finally, theres a third class of antivirals, called immune modulators, that seek to supercharge how our bodies naturally deal with infection. Interferons are proteins that whir into action at the first sign of an infection, kick-starting the immune response. Peginterferon lambda, a drug developed by Eiger Biopharmaceuticals, has shown exciting results in an early clinical trial. One shot of the drug cut risk of hospitalization by half when administered early in vaccinated patients and by 89 percent when administered early to unvaccinated patients. Glenn, who founded Eiger and sits on its board of directors, said the company plans to request emergency use authorization from the Food and Drug Administration.

Efficacy and ease of use arent the only factors that will shape the next iterations of covid antivirals. To be maximally effective, the drugs need to relatively inexpensive and easy to manufacture and distribute worldwide, Cherry said. Thats actually not so trivial, she said, but is key to ensuring the kind of equitable access that represents the worlds best bet toward controlling the pandemic.

But with unprecedented funding and interest in antivirals, many researchers are optimistic. Not only might the next generations of SARS-CoV-2 antivirals transform the nature of the pandemic, they might bolster our antiviral arsenal such that were better prepared for the next major infectious disease threat. Theres no limit to the creativity and novelty of all these new targets, Frieman said. Which ones work and which ones wont work, I dont know, but I think that the future is really bright for the number of antivirals that will be developed in the next decade.

An earlier version of this article misstated that Eiger Biopharmaceuticals had already requested emergency use authorization. This version has been corrected.

Thanks to Lillian Barkley for copy editing this article.

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Beyond Paxlovid for covid-19: The hunt for better covid medications - Grid