Category Archives: Molecular Medicine

Mingjian Du, Ph.D., (left) and Zhijian James Chen, Ph.D.

DALLAS June 02, 2022 Protein complexes that play a critical role in launching an immune response assemble in droplets that form within the liquid environment in cells much like oil droplets in water, UTSouthwestern scientists report in a new study. The findings, published in Molecular Cell, could lead to new interventions to regulate immunity in individuals with overactive or underactive immune responses.

These droplets basically function as microreactors that concentrate proteins and their substrates within. Its like forming compartments without needing membranes to surround them, said study leader Zhijian James Chen, Ph.D., Professor of Molecular Biology and Director of the Center for Inflammation Research at UTSW, a Howard Hughes Medical Institute Investigator, and winner of the 2019 Breakthrough Prize in Life Sciences.

More than two decades ago, the Chen lab discovered that a protein called ubiquitin assembles into chains inside cells when the cells are exposed to inflammatory molecules, such as interleukin-1 (IL-1) or tumor necrosis factor (TNF). Dr. Chen and his colleagues showed that the chains are key for promoting an immune response and can activate a group of proteins known as the IB complex (IKK), which includes a component known as NEMO. This complex in turn triggers a protein called NF-B to move to the nucleus and turn on hundreds of immune-related genes. But how the polyubiquitin chains, NEMO, and IKK come together has been unclear.

NEMO proteins are condensed in liquid droplets (red puncta) in the cytoplasm of a human cell in response to stimulation by a cytokine (interleukin-1). Blue shows the nucleus of the cell.

To answer this question, Dr. Chens team mixed ubiquitin and NEMO in test tubes with a protein called TRAF6, which promotes ubiquitin to assemble into chains. They saw that NEMO and the polyubiquitin chains assembled into liquid droplets that stayed separate from the liquid medium in the test tubes. Experiments in human cells showed that NEMO and the polyubiquitin chains displayed the same phase separation behavior after the cells were exposed to IL-1 or TNF. When IKK entered these droplets, it became activated and triggered NF-B to move to the nucleus. The longer the polyubiquitin chains, the larger the droplets they formed with NEMO and the stronger the immune response they triggered, Dr. Chen explained.

The team further studied this process using NEMO that was altered by mutations associated with a rare disease known as NEMO deficiency syndrome, which severely blunts immune response to bacterial infections. NEMO that carried these mutations could not effectively condense into droplets with polyubiquitin chains, preventing the cascade of events that triggers an immune response.

Dr. Chen noted that better understanding of this liquid phase separation phenomenon could eventually lead to treatments for NEMO deficiency syndrome and interventions to counteract overactive or underactive immunity, the root cause of autoimmune disorders and increased susceptibility to infection, respectively.

Dr. Chen is a George L. MacGregor Distinguished Chair in Biomedical Science and a member of the National Academy of Sciences.

Mingjian Du, Ph.D., a postdoctoral fellow in the Chen lab, is lead author of this study. Other UTSW researchers who contributed to this study include Chee-Kwee Ea and Yan Fang.

This research was supported by grants from the Cancer Prevention and Research Institute of Texas (RP180725, RP210041) and The Welch Foundation (I-1389).

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in more than 80 specialties to more than 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.

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Phase separation found in immune response within cells - UT Southwestern

According to a new report published by Grand View Research, the future market potential of genomics in newborn screening programs, emerging companies like Counsyl and Natera have launched various genetic tests to maintain their competitive edge in the market.

Genomics Industry Overview

The global genomics market size was valued at USD 20.1 billion in 2020 andis expected to reach USD 62.9 billion by 2028, expecting to expand at a CAGR of 15.35%during forecast period.

The scientific community has tried to address genetic susceptibility and severity to SARS-CoV-2 infection by combining research efforts using existing genetic databases. Multiomic-based approaches and genome-wide association studies (GWAS) have been employed to uncover biological networks and common variants underlying host-pathogen interactions. Similarly, data derived from genomes, such as polygenic risk scores (PRS), ABO blood groups, and HLA haplotypes, can be potentially used to decipher COVID-19 complications, resistance, and susceptibility. Moreover, biobanks that link electronic health records (EHRs) to genomic data can be leveraged to study the impact of genomic factors on the clinical course of patients infected with SARS-CoV-2.

Gather more insights about the market drivers, restrains and growth of the Global Genomics Market

The COVID-19 Host Genetics Initiative launched by researchers from the Finnish Institute for Molecular Medicine (FIMM) aims to inspire the human genetics community to analyze, share, and generate data to interpret determinants of COVID-19 outcomes, severity, and susceptibility. deCODE genetics, a genomics solutions provider in Iceland, has used SARS-CoV-2 genomic analysis to monitor the viral spread.

In addition, the company has partnered with the Government of Iceland to conduct genome sequencing of viral hosts. Similarly, the government of Greece funded the COVID-19-GR initiative to genotype 3,500 COVID-19 patients, conduct WGS on the SARS-CoV-2 genome obtained from these patients, and conduct immunogenomic analyses. The complete set of this data along with detailed clinical information is available and can be retrieved from the Greek COVID-19 registry.

In the near future, prenatal genetic screening programs are likely to grow at a significant pace. This is because these programs help expectant mothers identify chromosomal anomalies in their offspring. Moreover, it is anticipated that in the next 10 years, every newborns genome would be sequenced and stored in the electronic medical record. Gauging the future market potential of genomics in newborn screening programs, emerging companies like Counsyl and Natera have launched various genetic tests to maintain their competitive edge in the market.

Genomics Market Segmentation

Based on the Deliverable Insights, the market is segmented into product ad services

Based on the Application and Technology Insights, the market is segmented into functional genomics, pathway analysis, biomarker discovery, epigenetics and others

Based on End-use Insights, the market is segmented into pharmaceutical and biotechnology companies, hospitals and clinics, academic and government institutes, clinical research and other end users

Based on the Regional Insights, the market is segmented into North America, Europe, Asia Pacific, Latin America, and Middle East & Africa

Market Share Insights:

Key Companies Profile:

Companies are increasingly focusing on the development and launch of new products and collaboration with other entities to increase their market share.

Some prominent players in the global genomics market include:

Order a free sample PDF of the GenomicsMarket Intelligence Study, published by Grand View Research.

About Grand View Research

Grand View Research is a full-time market research and consulting company registered in San Francisco, California. The company fully offers market reports, both customized and syndicates, based on intense data analysis. It also offers consulting services to business communities and academic institutions and helps them understand the global and business scenario to a significant extent. The company operates across multitude of domains such as Chemicals, Materials, Food and Beverages, Consumer Goods, Healthcare, and Information Technology to offer consulting services.

Web: https://www.grandviewresearch.com

Media ContactCompany Name: Grand View Research, Inc.Contact Person: Sherry James, Corporate Sales Specialist U.S.A.Email: Send EmailPhone: 1888202951Address:Grand View Research, Inc. 201 Spear Street 1100 San Francisco, CA 94105, United StatesCity: San FranciscoState: CaliforniaCountry: United StatesWebsite: https://www.grandviewresearch.com/industry-analysis/genomics-market

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Genomics Market Size Is Expected To Reach $62.9 Billion By 2028, Based on High Demand For Advanced Gene-Editing Tools From Biotechnology Companies |...

How might waning immunity and reinfection affect our nextwave of COVID-19? Researchers have modelled differentscenarios to predict what the coming months might looklike.

The researchers found that a second COVID wavearose in the latter half of 2022 in all their scenarios,smaller than our first wave and set to peak in August toNovember depending on how fast immunity drops. However, ahigher peak of hospitalisations may occur if more olderpeople get infected. Under a faster-waning immunity scenariowith older ages more infected, this modelling estimates thatas many as 46% of cases could be reinfections.

The SMCasked experts to comment.

Dr Dianne Sika-Paotonu,Immunologist, Associate Dean (Pacific), Head of Universityof Otago Wellington Pacific Office, and Senior Lecturer,Pathology & Molecular Medicine, University of OtagoWellington, comments:

Waning immunity andreinfection

Many whove recovered from Covid-19will have developed immunity at least for the initial monthsfollowing infection, however reinfection risk with theSARS-CoV-2 virus remains. Although previous infection withthe virus does offer some immune protection, this does waneover time. More people have now been exposed to theSARS-CoV-2 virus, and with the emergence of the Omicronvariant, reinfections have been increasing in a way not seenwith earlier variants. Omicrons higher transmissibilityand ability to evade immune protection are likelycontributing factors.

Whats known from overseasstudies on reinfection risk

Towards the end of 2021as Omicron was spreading, data from South Africa was showinghigher reinfection rates when compared with previousinfection waves this pattern was also seen in othercountries. In the UK, the reinfection risk was found to be16 times greater when Omicron was the dominant variant,compared to when Delta dominated about seven months prior.This survey work was undertaken using random sampling ofhouseholds by the UK Office for NationalStatistics.

Data from England has also demonstrateda reinfection increase, where the rate of reinfections ofreported cases in February 2022 was about 10%, jumping fromjust 1% prior to mid-November 2021. One study from Qatar,which looked at the reinfection severity after initialinfection with the Alpha and Beta variants, indicated thatoverall, SARS-CoV-2 re-infections where anotherinfection occurred at least 90 days after the firstinfection tended to be less severe when compared withthe first infection.

Ongoing work will be needed tounderstand more about whether reinfections for Omicron andall its sub-variants are more or less severe, when comparedto the primary infection. It is still important that thosewho may have already had a Covid-19 infection furtherstrengthen their immunity withvaccination.

Overall, current evidence isindicating that reinfections have been increasing with theOmicron variant, and the risk of reinfection with theSARS-CoV-2 virus remains, especially for vulnerablecommunities.

Reinfection risk in NewZealand

Right now the daily reported COVID-19figures are still very high, and continue to place addedstrain and pressure on our health and other support systemsin Aotearoa New Zealand. The actual COVID-19 community casefigures are likely higher than those being reportedcurrently resulting from asymptomatic infection, and themajority of new community cases being detected by rapidantigen testing (RAT) with reliance on self-reporting ofresults. Reinfections in Aotearoa New Zealand will need tobe monitored carefully.

Impact of healthinequities

The COVID-19 pandemic has exacerbatedpre-existing inequities in health for vulnerablecommunities, and this includes for Mori and Pacificpeoples. It was known from the outset that Mori andPacific peoples were vulnerable to being disproportionatelyimpacted and affected by COVID-19 and therefore requiredprioritisation with respect to COVID-19 vaccination,prevention, and testing efforts. Inequities remain evidentwith vaccination and booster levels, and need to beaddressed with equity approaches that build trust and reducebarriers for people. Pacific peoples currently make up 11%of Covid-19 cases and more than double that 27% ofall hospitalisations.

Significant immunity gaps inAotearoa New Zealand exist right now as we move into winter.Children, tamariki and tamaiki aged 5-11 years still need tobe vaccinated against COVID-19 and many people are still toget COVID-19 boosters, with booster doses for the COVID-19vaccine now readily available for 16-17 year olds inAotearoa New Zealand.

Vaccination against otherillnesses

During the COVD-19 pandemic, there hasbeen limited exposure to other viruses such as the influenzavirus here in Aotearoa New Zealand, and there is potentialrisk of upcoming influenza outbreaks moving into winter. Wenow have more of the Influenza vaccines here being madeavailable for people these areimportant.

Lastly, although COVID-19 has been a keyfocus over the past two years, it is important to rememberthat all childhood vaccinations remain important. Regularchildhood vaccine schedules (non-COVID-19) for children,tamariki and tamaiki in Aotearoa New Zealand have beensignificantly affected by the Covid-19 pandemic. As aresult, there is potential risk of outbreaks for whoopingcough, measles and other illnesses that could be prevented.A resurgence of influenza and the respiratory syncytialvirus (RSV) could also possibly occur.

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Our aim is to promote accurate, evidence-based reporting on science and technology by helping the media work more closely with the scientific community.

The Science Media Centre is New Zealand's only trusted, independent source of information for the media on all issues related to science. Thousands of news stories providing context from and quoting New Zealand researchers have been published as a direct result of our work.

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Before coming down with COVID-19, Marjorie Roberts was known by friends and family as someone who always smiled.

On the morning of March 26, 2020, she was walking to her mailbox when she suddenly lost her balance and stumbled. At the moment, she didnt think much of it, but later that day, she describes feeling as though someone had [taken] a vacuum cleaner and sucked the life out of [her]. At 61 years old, she had never felt more sick in her lifeshe couldnt eat or sleep, suffered severe diarrhea and nightmares, and struggled to breathe. From that point on, she says, her life has not been the same.

Now, in 2022, her situation is only grimmer. She has developed spots on her liver, sarcoidosis in her lungs, and swollen lymph nodes. She also developed dry mouth so intense that it felt like someone was stuffing cotton in my mouth, as well as horrible bad breath. By the time she got to the dentist, seven teeth needed to come out. I always was the person who smiled, but now when I smile, the whole bottom of my mouth is gone, she says. Even if I wanted to take my mask off, I wont take it off, because COVID took my smile.

Pamela Bishop was a healthy, active, career-oriented professor at the University of Tennessee who had just launched her own research center before coming down with COVID-19 in December 2020. For the next three weeks, she says, she thought [she] was going to die every day. She suffered hallucinations, severe insomnia, and debilitating pain.

Bishop eventually recovered and returned to work in January 2021, but soon, she began having episodes of fatigue, brain fog, and nausea that forced her to lie down between meetings. The episodes increased in frequency until she realized she was horizontal more than she was up. I was sitting down to dinner with my husband [in March 2021] when I told him I didnt think I was getting better. I was damagedsomething was wrong with me, she says. This started the quest for figuring out what to do next.

Frank Ziegler used to go on long walks several times per week before January 14, 2021, when he thought he had developed a sinus infection. With a long history of these, he recognized the familiar pressure, stuffed ears, and drainage. But when he lost his sense of smell and received a positive result on his COVID-19 PCR test, he realized this wasnt a typical infection. Two months later, he began noticing hand tremors, cognitive issues, shortness of breath, and weight loss. Pre-COVID, I was very active and in good shape, he says. Now, just walking up the stairs puts me out of breath.

Millions of those who have recovered from COVID-19 are now experiencing a long string of often debilitating symptoms that persist weeks, months, or even two years or more following the original infection. As these long-haulers, most of whom are women, seek answers for their devastating and mysterious condition, many are also facing dismissal by their health care providers. Yale researchers Akiko Iwasaki, PhD, Sterling Professor of Immunobiology and Molecular, Cellular, Developmental Biology, professor of epidemiology (microbial diseases) and of dermatology, and investigator at the Howard Hughes Medical Institute (HHMI); and Harlan Krumholz, MD, Harold H. Hines, Jr. Professor of Medicine (Cardiology) and professor in the Institute for Social and Policy Studies, of investigative medicine, and of public health (health policy), are striving to solve the mysteries of long COVID, and to provide a compassionate voice for those feeling isolated and ignored by the medical community.

There are many people who have been infected with COVID who are suffering with an extraordinary set of symptoms, and yet, weve been unable to identify an approach which reflects their altered physiology, says Krumholz. However, their stories and experiences can help unlock what this is, and if we work together, we can make progress towards alleviating their suffering.

The Centers for Disease Control and Prevention (CDC) defines long COVID as having symptoms prolonging over four weeks after initial exposure to the virus, though according to Iwasaki, there is still no universal definition among scientists. The symptoms are highly variablelong-haulers have reported over 200 different symptoms. Common complaints include brain fog, shortness of breath, fatigue, difficulty concentrating, insomnia, tremors, gastrointestinal problems, palpitations, and both high and low blood pressure.

COVID-19 symptoms linger in approximately half to 75% of patients who suffered severe cases requiring hospitalization. But even among those who experienced mild or asymptomatic infections, many report developing persistent symptoms within the first two to three months after first being exposed. While there is not yet solid epidemiologic evidence on long COVID, Iwasaki estimates that between 10 and 30 percent of acute COVID-19 survivors develop the condition. Some people have mild cases of long COVID, but a significant number of people are disabled by this, says Iwasaki. Theyre suffering from financial difficulties because they cant work anymore, as well as the social and emotional impact of not being able to function in society.

One thing that is clear when I hear patients stories is that many people who were formerly extremely active and healthy have been relegated to a life where theyre able to do very little, says Krumholz. Someone just wrote to me today, saying that many of us [long-haulers] wish COVID had killed us because their lives have been so devastatingly affected.

Causes of long COVID are still unknown, but Iwasaki has several hypotheses. First, lingering viral remnants could be stimulating chronic inflammation. SARS-CoV-2 infection may also be triggering an autoimmune response within the body that leads to persistent symptoms. Long COVID could be the result of a latent virus like the Epstein-Barr virusthe pathogen that causes mononucleosisbecoming reactivated after COVID-19 infection. Tissue damage induced by infection that the body fails to repair properly could also be the culprit. These hypotheses, says Iwasaki, are not mutually exclusive, and many long-haulers may be suffering from a combination of these outcomes.

When Frank Ziegler began experiencing mysterious symptoms two months after coming down with COVID-19, he called his primary care provider (PCP). At the time, long COVID was just becoming a term, and he didnt yet know what it was. He wondered if he was the only person in the world to whom this was happening. My PCP basically patted me on my head and told me to go on my way, he says. I had only seen him for sinus infections through the yearshe knew Im not a hypochondriac.

Many long COVID patients, says Krumholz, are finding themselves in a similar position to Zieglers. There are no textbooks, no experts, no testing, and no treatments, says Krumholz. It makes it very difficult for patients, and they are often dismissed.

In her lab, Iwasaki is studying sex differences in the immune responses of people who develop long COVID. Of those who initially had a mild or asymptomatic infection that later developed into long COVID, she is finding, the majority are women between the ages of 20 and 60. Historically, medical conditions that predominantly impact women tend to be under-researched and ignored by the medical community, and this bias, she believes, may still affect attitudes when it comes to long COVID research and treatment.

It took a long time for medical researchers to recognize that this was a real disease, Iwasaki says. In the early days of the pandemic, womenas well as some menwere pretty much dismissed by their physicians, and some believed that it was all psychosomatic. And there are still physicians who believe this.

Marjorie Roberts and Pamela Bishop recall the frustration they felt when their health care providers wrote off their disabling symptoms as simply anxiety. My doctor told me that I was just mimicking what I saw on television, and that if I wanted to get better, I should watch Lifetime movies and do puzzles, says Roberts.

Bishop says she was also offered an antidepressant as the only option for treating the range of symptoms she was experiencing. When she later asked her provider for a referral to a specialist to treat her tinnitus, muscle cramps, fatigue, nausea, and other symptoms, she was again pushed to take the antidepressant. She was not offered any other options.

The fatigue you get from long COVID is not normal, and I knew this wasnt just anxiety, she says. She now attends a support group for long-haulers at Vanderbilt University, led by Vanderbilt professor and long Covid researcher James Jackson, PsyD, where 95 percent of the members are women. Bishop says many of the women also share similar stories of gaslighting or lack of awareness by medical professionals. When doctors tell you that nothing is wrong with you, you lose hope. Its dangerous.

Frank Ziegler first came across Krumholz after a friend had sent him an article from the Washington Post about long COVID. He was struck by the words of the Yale cardiologist, one of the doctors interviewed for the story, who called for providers to not dismiss the condition. I thought, 'there is a doctor that gets this! He understands, hes listening to his patients,' says Ziegler. Its a miracleI believe that. I dont believe in coincidences.

He decided to reach out via email on a Friday night, expressing his appreciation and sharing his own story. He didnt expect to get a reply, but to his surprise, Krumholz responded just two days later. Im not his patient, Im just someone from Nashville sending an email, says Ziegler. But he said he was really sorry for what I was going through, and he said that he would like to be able to talk to me more about this.

Ziegler told Krumholz about the Vanderbilt support group and expressed the groups desire to participate in research. Krumholz has teamed up with Iwasaki to launch the Yale LISTEN Study, or Listen to Immune, Symptom, and Treatment Experiences Now. More information can be found on Iwasaki and Krumholzs research on the Yale LISTEN study webpage.

The HHMI-funded project, part of the institutes broad support of COVID-related research at Yale, has two goals. First, its leaders plan to better understand the various patterns presented by long COVID by correlating specific biological signals with manifestations of the disease. They hope this will reveal underlying mechanisms that will help scientists develop appropriate, evidence-based therapeutics. Second, they hope the study will empower patients as they work together to find answers for their condition.

We want to do this study in a collaborative waythrough working in partnership with people and learning together, says Krumholz. We want to give patients agency over the data and enable them to make choices about the research they are a part of.

For many patients in the Vanderbilt support group, say Bishop and Ziegler, this is an exciting opportunity to take charge of their health. Many members of the group have been eager to enroll in medical studies, but finding a study to enroll in so far has been nearly impossible due to strict eligibility requirements of the limited number of trials available. Im looking forward to the LISTEN study. I am 100% on board, Bishop says. I have a lot to say, so a trial called LISTEN is perfect.

Indeed, both Iwasaki and Krumholz are dedicated to providing a compassionate ear to those in need. We see you, we recognize you, and we are doing everything we can to try and understand how this disease is mediated, says Iwasaki. We cant accept that this is going to be what it is and all these lives are going to unravel, says Krumholz. We have to do our best to move forward as teammates trying to push back the wave of ignorance and seeing if we can find things that work.

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Study Empowers Long COVID Patients as They Struggle to Find Relief - Yale School of Medicine

NEW YORK, June 03, 2022 (GLOBE NEWSWIRE) -- Applied Therapeutics, Inc. (Nasdaq: APLT), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, today announced designation of AT-007 (gavorestat) as an orphan medicinal product by the European Medicines Agency (EMA) for treatment of Galactosemia (Galactosaemia).

We are pleased that the EMA has recognized the high unmet medical need in Galactosemia, the role of galactitol as the toxic metabolite responsible for long-term complications in Galactosemia, and the potential benefit of AT-007 treatment in reducing toxic galactitol levels, said Shoshana Shendelman, PhD, Founder and CEO of Applied Therapeutics. Orphan designation for AT-007 marks an important step towards advancing our regulatory initiatives in Europe. We plan to meet with the EMA in the third quarter to discuss a potential MAA submission in Europe for conditional approval based on available biomarker data or for full approval based on expected clinical outcomes data.

Orphan medicinal product designation provides certain benefits and incentives in the EU, including protocol assistance, fee reductions, and ten years of market exclusivity once the medicine is on the market.

About Galactosemia

Galactosemia is a rare genetic metabolic disease resulting in an inability to metabolize the simple sugar galactose. Galactose is found in foods but is also produced endogenously by the body. When not metabolized properly, galactose is converted to the toxic metabolite, galactitol, which causes neurological complications, including deficiencies in speech, cognition, behavior, and motor skills, and also results in juvenile cataracts and ovarian insufficiency (in women). There are approximately 4,000 patients with Galactosemia in the EU and 120 new births per year.

About AT-007

AT-007 is a central nervous system (CNS) penetrant Aldose Reductase inhibitor (ARI) in development for the treatment of several rare neurological diseases, including Galactosemia, SORD Deficiency, and PMM2-CDG. In clinical trials, AT-007 significantly reduced plasma galactitol levels vs. placebo in adults and children with Galactosemia. AT-007 is currently being studied in a Phase 3 clinical outcomes trial (ACTION-Galactosemia Kids) in children ages 2-17 with Galactosemia, as well as a long-term open-label study in adults with Galactosemia. In a pilot study, AT-007 significantly reduced blood sorbitol levels in adults with SORD Deficiency. AT-007 is currently being studied in a Phase 3 trial (INSPIRE) investigating biomarker efficacy, clinical outcomes, and significantly reduced blood sorbitol levels in adults with SORD Deficiency. AT-007 has received both Orphan Drug and Pediatric Rare Disease designations from the U.S. Food and Drug Administration (FDA) for the treatment of Galactosemia and PMM2-CDG, and Fast Track designation for Galactosemia.

About Applied Therapeutics

Applied Therapeutics is a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need. The Companys lead drug candidate, AT-007, is a novel central nervous system penetrant Aldose Reductase Inhibitor (ARI) for the treatment of CNS rare metabolic diseases, including Galactosemia, SORD Deficiency, and PMM2-CDG. The Company is also developing AT-001, a novel potent ARI, for the treatment of Diabetic Cardiomyopathy, or DbCM, a fatal fibrosis of the heart. The preclinical pipeline also includes AT-003, an ARI designed to cross through the back of the eye when dosed orally, for the treatment of Diabetic retinopathy, as well as novel dual PI3k inhibitors in preclinical development for orphan oncology indications.

To learn more, please visit http://www.appliedtherapeutics.com and follow the company on Twitter @Applied_Tx.

Forward-Looking Statements

This press release contains forward-looking statements that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Any statements, other than statements of historical fact, included in this press release regarding strategy, future operations, prospects, plans and objectives of management, including words such as may, will, expect, anticipate, plan, intend, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are forward-looking statements. Forward-looking statements in this release involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we, therefore cannot assure you that our plans, intentions, expectations, or strategies will be attained or achieved.

Such risks and uncertainties include, without limitation, factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in our filings with the U.S. Securities and Exchange Commission, including the Risk Factors contained therein. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise.

Contacts

Investors:

Maghan Meyers(212) 600-1902 appliedtherapeutics@argotpartners.com

Media:

media@appliedtherapeutics.com

Applied Therapeutics, Inc.

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Applied Therapeutics Receives Orphan Medicinal Product Designation from the EMA for AT-007 for Treatment of Galactosemia - GlobeNewswire

In a bit of reverse engineering research using brain tissues from five people who died with Alzheimers disease, Johns Hopkins Medicine researchers say they discovered that a special sugar molecule could play a key role in the development of Alzheimers disease. If further research confirms the finding, the molecule, known as a glycan, could serve as a new target for early diagnostic tests, treatments and perhaps prevention of Alzheimers disease, say the researchers.

The study was published in theJournal of Biological Chemistry.

Alzheimers disease is the most common form of dementia in the United States. Affecting an estimated 5.8 million Americans, the progressive disorder occurs when nerve cells in the brain die due to the buildup of harmful forms of proteins called amyloid and tau.

Cleaning up the disease-causing forms of amyloid and tau is the job of the brains immune cells, called microglia. Earlier studies found that when cleanup is impaired, Alzheimers disease is more likely to occur. In some people, this is caused by an overabundance of a receptor on the microglia cells, called CD33.

Microglia cells function as macrophages in the central nervous system. They are the first immune cells to show up on the scene when something goes wrong in the brain and phagocytize various brain products, such as dying or dead cells.

Receptors are not active on their own. Something needs to connect with them to block microglia from cleaning up these toxic proteins in the brain, says Ronald Schnaar, Ph.D., the John Jacob Abel Professor of Pharmacology at the Johns Hopkins University School of Medicine and director of the laboratory that led the study.

Past studies by the researchers showed that for CD33, these connector molecules are special sugars. Known to scientists as glycans, these molecules are ferried around the cell by specialized proteins that help them find their appropriate receptors. The protein-glycan combination is called a glycoprotein.

In a bid to find out which specific glycoprotein connects with CD33, Schnaars research team obtained brain tissue from five people who died of Alzheimers disease and from five people who died from other causes from the Johns Hopkins Alzheimers Disease Research Center. Among the many thousands of glycoproteins they gathered from the brain tissues, only one connected to CD33.

To identify this mystery glycoprotein, the researchers first needed to separate it from the other brain glycoproteins. Since it was the only one in the brain that attached itself to CD33, they used this feature to catch it and separate it.

Glycans are made up of various sugar building blocks that influence the molecules interactions. Such sugars can be identified by their component parts. The researchers used chemical tools to deconstruct the glycan step by step, laying out the identity and order of its building blocks. The researchers identified the glycan portion of the glycoprotein as sialylated keratan sulfate.

Then, the researchers determined the protein components identity by taking its fingerprint using mass spectroscopy, which identifies protein building blocks. By comparing the molecular makeup of the protein with a database of known protein structures, the research team was able to conclude the protein portion of the glycoprotein was receptor tyrosine phosphatase (RPTP) zeta.

The researchers named the combined glycoprotein structure RPTP zeta S3L.

The group had previously found the same glycan signature on a protein that controls allergic responses in the airway, and that disrupting the glycan dampened allergic responses in mice.

We suspect the glycan signature carried on RPTP zeta may have a similar role in deactivating microglia through CD33, says Anabel Gonzalez-Gil Alvarenga, Ph.D., postdoctoral fellow in the Schnaar laboratory and first author of the study.

Further experiments showed that the brain tissue of the five people who died with Alzheimers disease had more than twice as much RPTP zeta S3L as the donors who did not have the disease. This implies that this glycoprotein may be connecting with more CD33 receptors than a healthy brain, limiting the brains ability to clean up harmful proteins.

Identifying this unique glycoprotein provides a step toward finding new drug targets and potentially early diagnostics for Alzheimers disease, says Gonzalez-Gil.

Next, the researchers plan to further study RPTP zeta S3Ls structure to determine how its attached glycans give the glycoprotein its unique ability to interact with CD33.

This article was republished with permission from Johns Hopkins Medicine. Read the original.

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Researchers link sugar-studded protein to Alzheimer's - ASBMB Today

Psychology Professor and Graduate School Associate Dean Tammy Barry has been named vice provost for graduate and professional education at Washington State University. She will assume the new position, which was formerly titled Graduate School dean, effective July1.

Barry, who holds a doctorate in clinical psychology, also has served as the director of WSUs clinical psychology doctoral program. As associate dean, she oversaw the Graduate School function of program assessment and review, represented the Graduate School on the Committee on Institutional Accreditation and Program Assessment, and worked with the Provosts Office to meet the needs of institutional accreditation processes.

I am am thrilled to welcome Dr.Barry to the academic leadership team, and I know that she will bring a renewed energy to graduate and professional education across the WSUsystem, said Elizabeth Chilton, WSUprovost and executive vicepresident. Dr.Barrys commitment to collaboration and strong leadership was apparent throughout the interview process. It is clear that she has a firm understanding of graduate education at WSU and is well respected by the Graduate Schools staff and members of the University community.

In her new role, Barry will be charged with creating a vision for dynamic growth and excellence in WSUs graduate and professional education programs. This will include collaborating with academic leadership system-wide to conduct a careful assessment of WSUs current support for graduate and professional education. This assessment will include engagement with faculty and graduate student stakeholders, research into national best practices in the administration of graduate and professional education, and recommendations for changes to WSUs administrative and supportive services.

Barry earned her PhD from the University of Alabama. She completed her pre-doctoral clinical internship in the Department of Psychiatry and Behavioral Neurobiology at the University of Alabama at Birmingham School of Medicine, followed by an NIH-funded post-doctoral research position in the Department of Psychology at the University of Alabama. She was licensed as a psychologist in 2001. Before joining the faculty at WSU, Barry was an adjunct professor at the University of Alabama and interim director of its autism clinic. She has held positions as a visiting assistant professor at the University of Louisville, a tenure-track assistant professor at Texas A&M University, and a tenured associate professor at the University of Southern Mississippi, where she also served as the director of the clinical psychology doctoral program.

Barry is assuming the new role as Lisa Gloss, who holds a PhD in biochemistry, steps down as the Dean of the Graduate School and returns to her associate professor faculty position in the School of Molecular Biosciences. Gloss has served as the dean for more than three years and has been a committed leader of graduate education for WSU.

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Barry named vice provost for graduate and professional education WSU Insider - WSU News

Donata Vercelli, MD, has been appointed as a Regents Professor, a title awarded to full professors who have garnered the most distinguished accomplishments in research, teaching, scholarship or creative work. Dr. Vercelli, professor of cellular and molecular medicine, associate director of the University of Arizona Health Sciences Asthma and Airway Disease Research Center, and a member of the BIO5 Institute, came to the UArizona College of Medicine Tucson in 1999.

I am delighted to join the Arizona Board of Regents in recognizing Dr. Vercellis extraordinary research in the interaction of genetic and environmental factors in the development of asthma and allergic diseases, said Michael D. Dake, MD, senior vice president for Health Sciences. Her investigations, which integrate basic and molecular epidemiologic approaches, have had a profound impact on the publics understanding of the development of asthma and allergic diseases.

A landmark study Dr. Vercelli co-authored, published in theNew England Journal of Medicine, showed that children growing up on Amish farms who were exposed to higher levels of microbial products were better protected from asthma than children with similar genetic backgrounds who were growing up on Hutterite farms with less microbial exposure.

Becoming a Regents Professor is a truly great honor because so many stars need to be aligned you need to have the enthusiastic support your colleagues, willing to identify and verbalize that je ne sais quoi that is supposed to set Regents Professors apart within a faculty with many excellent members; then you need the support of several international and national authorities in your field; and finally, all this needs to convince a demanding, multidisciplinary group of professors who send their recommendations to our president, said Dr. Vercelli. How can younotfeel humbled andask yourself, Why me?

Her research has led to several major prizes, grant funding totaling more than $40 million and national and international accolades. In 2010, she was elected to the Association of American Physicians. In 2018, she was elected secretary general of the Collegium Internationale Allergologicum an international group that examines the scientific and clinical problems in allergy and related branches of medicine and immunology. In eight years she will become president of the Collegium.

I believe what is special about UArizona Health Sciences is that while pursuing our scientific dream to understand how the environment and microbes can protect from asthma and allergies we took the road less traveled and dared do experiments no one thought could work, said Dr. Vercelli. But they did work, and very, very well. I am convinced that being at UArizona Health Sciences has nurtured and strengthened my ability to think boldly and innovatively because at its best, this is what UArizona Health Sciences is about.

Dr. Vercelli received her medical degree from the University of Florence in 1978 and trained in immunology at Boston Childrens Hospital/Harvard Medical School, where she was assistant professor of pediatrics from 1991 to 1994. She followed that appointment at the San Raffaele Scientific Institute in Milan, where she spent four years as director of the Molecular Immunoregulation Unit.

The title of Regents Professor is reserved for full professors whose exceptional achievements merit national and international distinction. Regents Professor appointments are limited to no more than 3% of the total number of the university's tenured and tenure-track faculty members.

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Dr. Donata Vercelli Appointed as Regents Professor | UArizona Health Sciences - University of Arizona

When we eat and then digest a meal, the nutrients and other useful components in the food are broken downor metabolizedand ultimately make their way to cells throughout the body. Each cell has its own power plant, called the mitochondria, which produces energy for the cells various processes as well as other tasks that help keep a cell healthy. By the time metabolites reach the cell, they are completely broken down and segregated from one another, so that each can play a role in specific functions that the mitochondria perform.

The process goes far beyond fueling power generation in the cell, according to Hongying Shen, PhD, assistant professor of cellular & molecular physiology at Yale School of Medicine and a member of Yales Systems Biology Institute. Mitochondria also house many other biochemical processes that are critical for cellular and organismal physiology, and that require trafficking in and out of all kinds of metabolites, including nucleotides, amino acids for protein, and lipids, she says.

In a study published May 5 in Nature Communications, Shen and her lab have identified the molecular machinery through which many of the metabolites reach inside the mitochondria.

They focus on the human SLC25 carrier family, the largest protein family responsible for metabolite translocation across the mitochondrial membrane. Each of the 53 transporters has a distinct assignment. They are structurally, sequence-wise, very similar to each other, says Shen, but they have this amazing specificity. One is dedicated to a certain type of nutrients, the other dedicated to other metabolites or nutrients. So there seems to be a very tight regulation in terms of specificity to recognize metabolites being transported.

This new knowledge may open the door to potential regulation of what enters the cell, with the goal of preventing or mitigating disease.

We are particularly interested in human diseases affecting the brain that include psychiatric disorders and neurodegenerative disorders, Shen explains. In fact, there have been de novo mutations in the gene SLC25A39 that have been implicated in autism. And also, A39 has been recently implicated in Parkinsons disease where oxidative stress was proposed as a pathological mechanism. In addition, according to Shen, the antioxidant metabolite glutathione, whose delivery route her lab also identified, may be of great interest to scientists studying cancer.

One day in the future, it is conceivable that biomarkers could associate conditions such as neurodegeneration with the metabolic processes that Shens lab is studying. That, she says, could lead to new treatments for disease. Then we can perhaps change our metabolism by diet and by nutrition and all kinds of methods to intervene with that. If we were able to discover these processes and identify the metabolites, can we use dietary intervention to slow the disease onset or disease progression? There's a long way to go [before we might accomplish that], but it's something.

The new study appears to lay a sound foundation for future work. Shen is encouraged that a different research team, working independently and from a different direction, recently produced similar conclusions about the mitochondrial glutathione transporter.

Read more:
The Molecular Machinery That Delivers Metabolites to Mitochondria - Yale School of Medicine

What: Precision Health Care for All: The University of Arizona Health Sciences Center for Advanced Molecular and Immunological Therapies Lecture

When: Tuesday, May 17, 5:30 p.m.

Where: Health Sciences Education Building, 475 N. 5th Street, Phoenix

Register here: https://events.trellis.arizona.edu/en/f44lNu67/5a3U3nDxV11

Note: Media who wish to attend should contact Margarita Bauz at mbauza@arizona.edu.

The recently announced University of Arizona Health Sciences Center for Advanced Molecular and Immunological Therapies, known as CAMI, has garnered the support and involvement of more than 20 leaders in academic research, biomedical and health care industries, government organizations and corporations across the state.

The experts in their respective fields are members of the CAMI advisory committee, working in one of three targeted areas: Leadership and Organization; Program and Development; and Space, Design and Construction.

The University of Arizona Health Sciences has unique expertise in basic science, translational medicine and investigator-led clinical trials that will allow us to lead the nation in advanced immunotherapies research and the pursuit of innovative treatments, said Michael D. Dake, MD, senior vice president of the University of Arizona Health Sciences. Each of the advisory committee members are leaders in their respective fields, and their contributions will help ensure the success of the Center for Advanced Molecular and Immunological Therapies.

The CAMI advisory committee members are:

Dr. Dake will give a presentation about CAMI as part of UArizona Health Sciences Tomorrow is Here Lecture Series on Tuesday, May 17, at the Phoenix Bioscience Core campus.

The presentation, Precision Health Care for All: The University of Arizona Health Sciences Center for Advanced Molecular and Immunological Therapies, will begin at 5:30 p.m. in the Health Sciences Education Building, 475 N. 5th Street, Phoenix. Complimentary parking and refreshments will be provided, and online registration is required.

CAMI will serve as the anchor for an innovation district that aims to differentiate Phoenix from other emerging life sciences hubs, establishing the Phoenix Bioscience Core as a center of cell and gene therapy research, startup activity and corporate engagement. The centers location in Phoenix is expected to facilitate strong connections with partners such as Arizona State University, Northern Arizona University, the Mayo Clinic and the Translational Genomics Research Institute, while boosting the local economy in the process.

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New UArizona Health Sciences Center for Advanced Molecular and Immunological Therapies in Phoenix Guided by Diverse Group of Experts | UArizona Health...