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Can new emerging treatments cure pulmonary hypertension? – Labiotech.eu

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Pulmonary hypertension is a complex cardiovascular disorder characterized by high blood pressure in the pulmonary arteries, the vessels that carry blood from the heart to the lungs. This condition can lead to severe health complications, including heart failure, if not managed effectively. Historically, it has been about managing pulmonary hypertension’s symptoms but the industry is working on new treatments for this condition.

Recent advancements in biotechnology have marked a new era for pulmonary hypertension patients, transforming a once grim prognosis into a more manageable condition. Yet, despite these advances, pulmonary hypertension remains a challenging disease to treat. The disease’s heterogeneity means that effective treatment requires precise tailoring. In this article, we delve into the new treatment advances in pulmonary hypertension.

Table of contents

    Understanding pulmonary hypertension

    Pulmonary hypertension is broadly classified into five groups based on its cause and mechanism. Each type has unique pathophysiological features and treatment approaches, highlighting the complexity of diagnosing and managing pulmonary hypertension​.

    Symptoms of pulmonary hypertension can be non-specific and worsen over time. Common symptoms include shortness of breath during routine activities, fatigue, chest pain, and a racing heartbeat. As the condition progresses, symptoms can become more severe, even appearing at rest.

    Pulmonary hypertension is a relatively rare condition but can be devastating to those affected. The prevalence varies depending on the type of pulmonary hypertension, with Pulmonary arterial hypertension (PAH) affecting approximately 500 to 1,000 new individuals each year in the U.S. alone. The disease significantly impacts quality of life, limiting physical activities and leading to severe complications if untreated. Advanced pulmonary hypertension can lead to right heart failure due to the increased workload on the right ventricle, which must pump blood against the high pressure in the pulmonary arteries​​.

    Evolution of pulmonary hypertension treatment: from symptom management to targeted therapies

    Approaches to treating pulmonary hypertension have evolved significantly over the decades. Initially, treatment options were scarce and primarily focused on symptom management rather than addressing the underlying pathology of the disease. Early interventions included the use of conventional therapies such as anticoagulants and diuretics to manage associated conditions like edema and prevent thrombosis, which were often inadequate in altering the disease progression.

    The introduction of epoprostenol in the 1990s marked the first disease-specific treatment for PAH. As a synthetic analog of prostacyclin, epoprostenol helped to reduce pulmonary vascular resistance and improve survival rates, although its use was limited by the need for continuous intravenous administration and its short half-life, requiring complex management strategies​.

    Current standard therapies for pulmonary hypertension

    Modern treatment strategies for pulmonary hypertension have expanded to include a variety of targeted pharmacological interventions that more effectively manage the disease:

    • Vasodilators: These are crucial in the management of pulmonary hypertension, particularly PAH, and include agents such as prostacyclins, which directly dilate the pulmonary arteries and reduce arterial pressure.
    • Endothelin Receptor Antagonists (ERAs): These drugs, such as bosentan, ambrisentan, and macitentan, inhibit endothelin, a potent vasoconstrictor, thereby improving symptoms and exercise capacity.
    • Phosphodiesterase-5 Inhibitors: Sildenafil and tadalafil are examples that help relax the pulmonary arteries and increase blood flow.
    • Soluble Guanylate Cyclase (sGC) Stimulators: For example, riociguat can help relax and widen the blood vessels in the lungs​​.

    These treatments are supplemented by supportive measures such as oxygen therapy, diuretics, and anticoagulants, which help manage symptoms and improve quality of life but do not halt disease progression.

    Recent FDA approvals in the treatment of pulmonary hypertension

    FDA approval of Merck’s activin signalling inhibitor sotatercept

    Merck’s WINREVAIR (sotatercept-csrk) has marked a significant advancement in the treatment of pulmonary arterial hypertension. As the first FDA-approved activin signaling inhibitor therapy for PAH, WINREVAIR works by modulating the balance between pro-proliferative and anti-proliferative signaling pathways, which are crucial in vascular cell proliferation – a fundamental process in the pathophysiology of PAH.

    Clinical benefits highlighted in the STELLAR study include significant improvements in exercise capacity and pulmonary vascular resistance. Specifically, WINREVAIR demonstrated an 84% reduction in the risk of death or clinical worsening of PAH compared to placebo, and significant reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, a marker for heart stress. Moreover, the treatment has shown improvements in patients’ functional abilities and quality of life​​.

    FDA approval of J&J’s Opsynvi

    The FDA has recently approved other treatments that bring new hope to PAH patients. For instance, J&J’s Opsynvi, a once-daily, fixed-dose tablet combining macitentan and tadalafil, has been approved. This combination leverages the benefits of both an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor, simplifying treatment regimens for patients by reducing the number of medications they need to manage their condition daily​​.

    Current research and clinical trials in pulmonary hypertension treatment

    Highlighting research on restoring the TSC2 growth suppressor

    Research at UC Davis Health has uncovered promising results regarding the restoration of the tuberous sclerosis complex 2 (TSC2) growth suppressor, which may lead to reversing pulmonary vascular remodeling in PAH. This novel approach aims to target and potentially reverse the pathological changes in the pulmonary arteries that contribute to the high blood pressure observed in PAH patients. By restoring the function of TSC2, it might be possible to reduce the thickening of the pulmonary artery walls, thereby alleviating the high blood pressure in the lungs and improving overall heart function​​.

    Potential of tyrosine kinase pathway inhibitors

    Tyrosine kinase inhibitors, such as Imatinib, have shown promise in treating PAH by targeting the PDGF (platelet-derived growth factor) pathways, which are involved in the disease’s vascular remodeling processes. The IMPRES trial sponsored by Novartis indicated that Imatinib could improve pulmonary vascular resistance and overall cardiac output in patients with advanced symptoms, highlighting its potential as a supplementary therapy for those not adequately managed by conventional treatments. However, the drug’s side effects such as subdural hematomas, and dropouts due to intolerance, have tempered enthusiasm for its broad use, underscoring the need for careful patient selection and management​​.

    SPHK2/S1P axis and its role in epigenetic mechanisms

    The SPHK2 (sphingosine kinase 2)/S1P (sphingosine-1-phosphate) signaling pathway is another area of intense research focus. This pathway has been identified for its role in the epigenetic regulation of pulmonary vascular remodeling in pulmonary hypertension. By influencing histone acetylation processes, SPHK2 alters gene expression in vascular smooth muscle cells, potentially reversing harmful vascular changes. Initial studies suggest that targeting this axis could provide a new therapeutic approach to treat or even reverse aspects of pulmonary hypertension, although further research is needed to fully understand its efficacy and safety​​.

    Exploring stem cell therapies for pulmonary hypertension

    Stem cell therapies, including induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs), present promising approaches for treating pulmonary hypertension. These cells can differentiate into various cell types needed to repair damaged tissues, potentially reversing the effects of diseases like pulmonary hypertension. In particular, iPSCs, derived from adult cells, can be programmed to act similarly to embryonic stem cells, offering a versatile tool for regenerating diseased lung tissue. MSCs, on the other hand, have shown capabilities in modulating immune responses and ameliorating inflammatory conditions within the pulmonary vasculature, which are crucial aspects of pulmonary hypertension pathology​.

    One notable trial in this is the ALPHA phase 1a/b study,  investigating the safety and efficacy of a novel cell therapy developped by Capricor Therapeutics, CAP-1002. This therapy uses cardiosphere-derived cells (CDCs), which are progenitor heart cells capable of releasing signaling molecules that promote heart health. Unlike fully differentiated heart cells, progenitor cells have the potential to become various types of cells within the heart. This makes them an important focus for regenerative medicine, particularly in treating heart diseases. The trial primarily assesses the safety of CAP-1002 infusions in patients with pulmonary arterial hypertension who are already on PAH-specific medication. 

    Looking to the future of pulmonary hypertension treatment

    The next decade in pulmonary hypertension treatment is poised to witness significant advancements, driven by rapid developments in biotechnology and a deeper understanding of the disease’s molecular underpinnings. We can expect further refinement and expansion of targeted therapies such as those modulating the activin signaling pathways, as well as the introduction of new classes of drugs that could more effectively halt or even reverse disease progression. Additionally, advancements in drug delivery systems, such as nanoparticle technologies, may enhance the efficacy and reduce the side effects of existing treatments.

    Personalized medicine is set to play a pivotal role in transforming the treatment landscape for pulmonary hypertension. As genetic profiling becomes more sophisticated and accessible, it will allow for more precise identification of the forms of pulmonary hypertension at a molecular level, leading to more customized treatment plans. This approach will not only improve the efficacy of treatments but also minimize adverse effects by tailoring therapies based on individual genetic backgrounds and disease phenotypes. The integration of genomic data with clinical practice could lead to the development of predictive models to guide therapy choices and improve outcomes for patients with pulmonary hypertension​.

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    Health Canada approves updated Moderna COVID-19 vaccine

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    TORONTO – Health Canada has authorized Moderna’s updated COVID-19 vaccine that protects against currently circulating variants of the virus.

    The mRNA vaccine, called Spikevax, has been reformulated to target the KP.2 subvariant of Omicron.

    It will replace the previous version of the vaccine that was released a year ago, which targeted the XBB.1.5 subvariant of Omicron.

    Health Canada recently asked provinces and territories to get rid of their older COVID-19 vaccines to ensure the most current vaccine will be used during this fall’s respiratory virus season.

    Health Canada is also reviewing two other updated COVID-19 vaccines but has not yet authorized them.

    They are Pfizer’s Comirnaty, which is also an mRNA vaccine, as well as Novavax’s protein-based vaccine.

    This report by The Canadian Press was first published Sept. 17, 2024.

    Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

    The Canadian Press. All rights reserved.

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    These people say they got listeria after drinking recalled plant-based milks

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    TORONTO – Sanniah Jabeen holds a sonogram of the unborn baby she lost after contracting listeria last December. Beneath, it says “love at first sight.”

    Jabeen says she believes she and her baby were poisoned by a listeria outbreak linked to some plant-based milks and wants answers. An investigation continues into the recall declared July 8 of several Silk and Great Value plant-based beverages.

    “I don’t even have the words. I’m still processing that,” Jabeen says of her loss. She was 18 weeks pregnant when she went into preterm labour.

    The first infection linked to the recall was traced back to August 2023. One year later on Aug. 12, 2024, the Public Health Agency of Canada said three people had died and 20 were infected.

    The number of cases is likely much higher, says Lawrence Goodridge, Canada Research Chair in foodborne pathogen dynamics at the University of Guelph: “For every person known, generally speaking, there’s typically 20 to 25 or maybe 30 people that are unknown.”

    The case count has remained unchanged over the last month, but the Public Health Agency of Canada says it won’t declare the outbreak over until early October because of listeria’s 70-day incubation period and the reporting delays that accompany it.

    Danone Canada’s head of communications said in an email Wednesday that the company is still investigating the “root cause” of the outbreak, which has been linked to a production line at a Pickering, Ont., packaging facility.

    Pregnant people, adults over 60, and those with weakened immune systems are most at risk of becoming sick with severe listeriosis. If the infection spreads to an unborn baby, Health Canada says it can cause miscarriage, stillbirth, premature birth or life-threatening illness in a newborn.

    The Canadian Press spoke to 10 people, from the parents of a toddler to an 89-year-old senior, who say they became sick with listeria after drinking from cartons of plant-based milk stamped with the recalled product code. Here’s a look at some of their experiences.

    Sanniah Jabeen, 32, Toronto

    Jabeen says she regularly drank Silk oat and almond milk in smoothies while pregnant, and began vomiting seven times a day and shivering at night in December 2023. She had “the worst headache of (her) life” when she went to the emergency room on Dec. 15.

    “I just wasn’t functioning like a normal human being,” Jabeen says.

    Told she was dehydrated, Jabeen was given fluids and a blood test and sent home. Four days later, she returned to hospital.

    “They told me that since you’re 18 weeks, there’s nothing you can do to save your baby,” says Jabeen, who moved to Toronto from Pakistan five years ago.

    Jabeen later learned she had listeriosis and an autopsy revealed her baby was infected, too.

    “It broke my heart to read that report because I was just imagining my baby drinking poisoned amniotic fluid inside of me. The womb is a place where your baby is supposed to be the safest,” Jabeen said.

    Jabeen’s case is likely not included in PHAC’s count. Jabeen says she was called by Health Canada and asked what dairy and fresh produce she ate – foods more commonly associated with listeria – but not asked about plant-based beverages.

    She’s pregnant again, and is due in several months. At first, she was scared to eat, not knowing what caused the infection during her last pregnancy.

    “Ever since I learned about the almond, oat milk situation, I’ve been feeling a bit better knowing that it wasn’t something that I did. It was something else that caused it. It wasn’t my fault,” Jabeen said.

    She’s since joined a proposed class action lawsuit launched by LPC Avocates against the manufacturers and sellers of Silk and Great Value plant-based beverages. The lawsuit has not yet been certified by a judge.

    Natalie Grant and her seven year-old daughter, Bowmanville, Ont.

    Natalie Grant says she was in a hospital waiting room when she saw a television news report about the recall. She wondered if the dark chocolate almond milk her daughter drank daily was contaminated.

    She had brought the girl to hospital because she was vomiting every half hour, constantly on the toilet with diarrhea, and had severe pain in her abdomen.

    “I’m definitely thinking that this is a pretty solid chance that she’s got listeria at this point because I knew she had all the symptoms,” Grant says of seeing the news report.

    Once her daughter could hold fluids, they went home and Grant cross-checked the recalled product code – 7825 – with the one on her carton. They matched.

    “I called the emerg and I said I’m pretty confident she’s been exposed,” Grant said. She was told to return to the hospital if her daughter’s symptoms worsened. An hour and a half later, her fever spiked, the vomiting returned, her face flushed and her energy plummeted.

    Grant says they were sent to a hospital in Ajax, Ont. and stayed two weeks while her daughter received antibiotics four times a day until she was discharged July 23.

    “Knowing that my little one was just so affected and how it affected us as a family alone, there’s a bitterness left behind,” Grant said. She’s also joined the proposed class action.

    Thelma Feldman, 89, Toronto

    Thelma Feldman says she regularly taught yoga to friends in her condo building before getting sickened by listeria on July 2. Now, she has a walker and her body aches. She has headaches and digestive problems.

    “I’m kind of depressed,” she says.

    “It’s caused me a lot of physical and emotional pain.”

    Much of the early days of her illness are a blur. She knows she boarded an ambulance with profuse diarrhea on July 2 and spent five days at North York General Hospital. Afterwards, she remembers Health Canada officials entering her apartment and removing Silk almond milk from her fridge, and volunteers from a community organization giving her sponge baths.

    “At my age, 89, I’m not a kid anymore and healing takes longer,” Feldman says.

    “I don’t even feel like being with people. I just sit at home.”

    Jasmine Jiles and three-year-old Max, Kahnawake Mohawk Territory, Que.

    Jasmine Jiles says her three-year-old son Max came down with flu-like symptoms and cradled his ears in what she interpreted as a sign of pain, like the one pounding in her own head, around early July.

    When Jiles heard about the recall soon after, she called Danone Canada, the plant-based milk manufacturer, to find out if their Silk coconut milk was in the contaminated batch. It was, she says.

    “My son is very small, he’s very young, so I asked what we do in terms of overall monitoring and she said someone from the company would get in touch within 24 to 48 hours,” Jiles says from a First Nations reserve near Montreal.

    “I never got a call back. I never got an email”

    At home, her son’s fever broke after three days, but gas pains stuck with him, she says. It took a couple weeks for him to get back to normal.

    “In hindsight, I should have taken him (to the hospital) but we just tried to see if we could nurse him at home because wait times are pretty extreme,” Jiles says, “and I don’t have child care at the moment.”

    Joseph Desmond, 50, Sydney, N.S.

    Joseph Desmond says he suffered a seizure and fell off his sofa on July 9. He went to the emergency room, where they ran an electroencephalogram (EEG) test, and then returned home. Within hours, he had a second seizure and went back to hospital.

    His third seizure happened the next morning while walking to the nurse’s station.

    In severe cases of listeriosis, bacteria can spread to the central nervous system and cause seizures, according to Health Canada.

    “The last two months have really been a nightmare,” says Desmond, who has joined the proposed lawsuit.

    When he returned home from the hospital, his daughter took a carton of Silk dark chocolate almond milk out of the fridge and asked if he had heard about the recall. By that point, Desmond says he was on his second two-litre carton after finishing the first in June.

    “It was pretty scary. Terrifying. I honestly thought I was going to die.”

    Cheryl McCombe, 63, Haliburton, Ont.

    The morning after suffering a second episode of vomiting, feverish sweats and diarrhea in the middle of the night in early July, Cheryl McCombe scrolled through the news on her phone and came across the recall.

    A few years earlier, McCombe says she started drinking plant-based milks because it seemed like a healthier choice to splash in her morning coffee. On June 30, she bought two cartons of Silk cashew almond milk.

    “It was on the (recall) list. I thought, ‘Oh my God, I got listeria,’” McCombe says. She called her doctor’s office and visited an urgent care clinic hoping to get tested and confirm her suspicion, but she says, “I was basically shut down at the door.”

    Public Health Ontario does not recommend listeria testing for infected individuals with mild symptoms unless they are at risk of developing severe illness, such as people who are immunocompromised, elderly, pregnant or newborn.

    “No wonder they couldn’t connect the dots,” she adds, referencing that it took close to a year for public health officials to find the source of the outbreak.

    “I am a woman in my 60s and sometimes these signs are of, you know, when you’re vomiting and things like that, it can be a sign in women of a bigger issue,” McCombe says. She was seeking confirmation that wasn’t the case.

    Disappointed, with her stomach still feeling off, she says she decided to boost her gut health with probiotics. After a couple weeks she started to feel like herself.

    But since then, McCombe says, “I’m back on Kawartha Dairy cream in my coffee.”

    This report by The Canadian Press was first published Sept. 16, 2024.

    Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

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    B.C. mayors seek ‘immediate action’ from federal government on mental health crisis

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    VANCOUVER – Mayors and other leaders from several British Columbia communities say the provincial and federal governments need to take “immediate action” to tackle mental health and public safety issues that have reached crisis levels.

    Vancouver Mayor Ken Sim says it’s become “abundantly clear” that mental health and addiction issues and public safety have caused crises that are “gripping” Vancouver, and he and other politicians, First Nations leaders and law enforcement officials are pleading for federal and provincial help.

    In a letter to Prime Minister Justin Trudeau and Premier David Eby, mayors say there are “three critical fronts” that require action including “mandatory care” for people with severe mental health and addiction issues.

    The letter says senior governments also need to bring in “meaningful bail reform” for repeat offenders, and the federal government must improve policing at Metro Vancouver ports to stop illicit drugs from coming in and stolen vehicles from being exported.

    Sim says the “current system” has failed British Columbians, and the number of people dealing with severe mental health and addiction issues due to lack of proper care has “reached a critical point.”

    Vancouver Police Chief Adam Palmer says repeat violent offenders are too often released on bail due to a “revolving door of justice,” and a new approach is needed to deal with mentally ill people who “pose a serious and immediate danger to themselves and others.”

    This report by The Canadian Press was first published Sept. 16, 2024

    The Canadian Press. All rights reserved.

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