J&J Gets CDSCO Panel Nod to study anti-cancer drug Talquetamab

New Delhi: The drug major Johnson and Johnson has got approval from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) to conduct the phase III clinical study of the anti-cancer drug Talquetamab.

This came after the firm presented Phase III Clinical Study Protocol No. 64407564MMY3009.

Talquetamab is a bispecific antibody used to treat adults with relapsed or refractory multiple myeloma.

Talquetamab is an IgG4-PAA bispecific G protein-coupled receptor class C group 5 member D (GPRC5D)-directed CD3 T-cell engager. It consists of two arms – anti-GPRC5D and anti-CD3 arms – linked by two interchain disulfide bonds, each arm comprising a heavy and light chain. Talquetamab binds to GPRC5D, a cell surface receptor expressed predominantly on multiple myeloma cells, and CD3 on T cells. It works to recruit CD3-expressing T cells to GPRC5D-expressing multiple myeloma cells to induce T-cell–mediated cytotoxicity.

At the recent SEC meeting for Oncology and Hematology held on 29th and 30th November 2023, the expert panel reviewed the Phase III Clinical Study Protocol of the anti-cancer drug Talquetamab presented by drug major Johnson and Johnson.
After detailed deliberation, the committee recommended the grant of permission to conduct the trial as presented by the firm.

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Use of opioids in Surgery patients declining: JAMA

Post-surgery pain relief has shifted away from opioid-containing medications over the past seven years, but the downward trend has slowed since 2020, a new study shows.

Overall, the rate of surgery-related opioid prescriptions dropped by 36% from 2016 to the end of 2022, and the average amount of opioids in those prescriptions dropped by 46%, the study of pharmacy data finds.

That combination of declines means that the total amount of opioids dispensed to surgical patients in late 2022 was 66% lower compared with early 2016, according to the findings published in JAMA Network Open by a team from the University of Michigan.

But the rate of decline was much faster before the pandemic, the researchers report after comparing surgical opioid patterns before and after 2020. That’s even after they took into account the unusual circumstances of spring 2020, when most elective surgery temporarily stopped to free up hospital capacity for COVID-19 patients and reduce unnecessary exposure to the SARS-CoV-2 virus.

Even with the overall declines, American surgery patients in late 2022 still received the equivalent of 44 5-milligram pills of hydrocodone from pharmacies after their operations on average. That’s far higher than what patients need for most procedures.

“These data suggest surgical teams have substantially reduced opioid prescribing, but also suggest that efforts to right-size opioid prescriptions after surgery must continue,” said Kao-Ping Chua, M.D., Ph.D., the senior author of the new study and an assistant professor of pediatrics at U-M. He worked with first author and former U-M research assistant Jason Zhang, who is now in medical school at Northwestern University.

The researchers also find that some types of surgeons have reduced the amount of opioids dispensed to patients more than others. For instance, reductions were particularly large in cardiothoracic surgery and ophthalmology.

Orthopedic surgeons still account for more than half of all surgical opioids dispensed to American patients, even as the rate and size of prescriptions filled by their patients dropped.

Right-sizing prescribing

The authors note that surgeons should not strive to eliminate opioid prescribing altogether.

“The goal should be to ensure that opioids are only prescribed when necessary, and that the amount of opioids prescribed matches the amount that patients need,” said Zhang. “Achieving these goals could help reduce the risk of opioid misuse, persistent opioid use, and diversion of pills to other people besides the patient.”

The potential for accidental exposure to opioids by others in the household, and interactions between opioids and other substances including alcohol and prescription drugs, are other reasons to focus on non-opioid surgical pain care.

Chua and colleagues have studied procedure-related opioid prescribing multiple times, including a recent study showing that the reduction in the rate of dental opioid prescribing has similarly slowed in recent years.

They have worked with the Michigan Opioid Prescribing Engagement Network (OPEN) to develop prescribing guidelines for adult and pediatric surgical care available at https://michigan-open.org/prescribing-recommendations

Surgical organizations and the Centers for Disease Control and Prevention have advised surgeons to rely less on opioid-based acute pain relief for their patients since the mid-2010s. But no studies have examined surgical opioid prescribing trends using pandemic-era data.

The new study is based on data from a company called IQVIA that tracks prescriptions dispensed at 92% of U.S. pharmacies.

Reference:

Zhang J, Waljee JF, Nguyen TD, et al. Opioid Prescribing by US Surgeons, 2016-2022. JAMA Netw Open. 2023;6(12):e2346426. doi:10.1001/jamanetworkopen.2023.46426.

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PG Medico Suicide Case: Kerala HC grants bail to doctor accused of dowry demands

Thiruvananthapuram: In a significant development, the Kerala High Court on Friday, approved the bail application of a doctor who had faced suspension from the Indian Medical Association (IMA) following accusations of abetting the suicide of his girlfriend.

Medical Dialogues team had earlier reported that the victim, a second-year postgraduate surgery trainee at Government Medical College, Thiruvananthapuram, took her own life after the accused cancelled their wedding plans due to alleged dowry demands.
The allegations suggest that the family of the accused had sought 150 sovereigns of gold, 15 acres of land, and a BMW car from the family of the deceased. Unfortunately, her family was unable to fulfill these demands, leading to the tragic incident. Subsequently, the IMA suspended the accused doctor’s medical license for his alleged involvement in abetting the suicide.

The accused has been charged with offenses under Section 306 IPC (‘Abetment of Suicide’) and Section 4 of the Dowry Prohibition Act (‘Penalty for demanding dowry’). The bail plea was considered by Justice Gopinath P, who, taking into account the accused’s custody since December 7, 2023, concluded that further detention was unnecessary for investigative purposes and allowed for his release on bail, reports LiveLaw. 

“The allegations against the petitioner are no doubt serious. I had also observed while granting bail to the 2nd accused in the case (Ruvais’ father), that there are clear allegations against the petitioner in the suicide note recovered from the apartment where the deceased was staying. However, as rightly pointed out by the Senior Counsel appearing for the petitioner, a condition under Section 306 IPC can be sustained only if there are clear indications that the petitioner had the mens rea to drive the deceased to suicide, and the actions of the petitioner had left the deceased with no option but to commit suicide,” the Court observed.

The Court had previously granted anticipatory bail to Ruwais’s father, who was also named as the second accused in the case. In the bail application presented by Advocate Nireesh Mathew on behalf of the accused, it was asserted that there was no substantial evidence linking him to the alleged offense. He argued that the relationship between him and the victim had reached a stage where they started talking about a marriage proposal. However, his father had suggested delaying the marriage until the completion of education, a proposal that the victim found unacceptable. The petitioner contended that the victim was pressuring him to marry her against his father’s advice, a decision he chose not to follow. The doctor refused to accept that any conversation regarding any kind of dowry ever took place between the two families. 

Also Read:Kerala doctor involved in girlfriend suicide case over dowry demands suspended by IMA

The counsel for the accused further argued that the suicide did not result from immediate provocation or instigation, as required by Section 306 IPC. He asserted that he had no intention to harm the victim but had genuinely expressed his desire to marry her. During the hearing, the potential damage to his career and future and the seizure of his belongings, including a laptop and car has also been highlighted. To continue studying alone, he requested bail, even with strict terms attached, such as his inability to leave the College and hostel grounds, reports The Daily. The accused also stated that the doctor should not have taken such a cruel step thoughtlessly. 

The prosecution argued that decisions regarding the accused’s reinstatement in service should be made by the Disciplinary Committee in consultation with the Department of Health, Government of Kerala, and the Kerala University of Health Sciences. The prosecution stressed that the petitioner’s desire to continue his studies was insufficient grounds for bail, as the decision on his course continuation remained pending.

After careful consideration, the Court made it clear that the doctor’s request for bail could not be seen as an entitlement to reinstatement; rather, it should only be resolved in compliance with the relevant legislation, even though the Court granted him a request, it is subjected to certain conditions and regulation. 

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Conduct bioequivalence study: CDSCO Panel tells Zydus Healthcare on Glycopyrrolate, Indacaterol Metered dose inhalation

New Delhi: Rejecting the clinical trial waiver proposal, the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has opined the drug major Zydus Healthcare to conduct a bioequivalence study (BE) of Glycopyrrolate plus Indacaterol Maleate Metered dose inhalation.

This came after Zydus Healthcare presented a proposal along with BE protocol and justification for clinical trial waiver before the committee.

Glycopyrrolate is an anticholinergic agent used to treat hyperhidrosis, severe drooling, and COPD, used with other medications to treat ulcers, and used in anesthesia. Glycopyrrolate is a racemic mixture of two enantiomers. They are both quaternary ammonium compounds and long-acting muscarinic antagonists. It is one of the most commonly prescribed anticholinergic medications. Glycopyrronium is a muscarinic antagonist with the highest affinity for M1 receptors, followed by M3, M2/M4, and M5.

Indacaterol is an inhaled long-acting beta-2 adrenergic agonist used to relax bronchial smooth muscle and improve symptoms and airflow obstruction caused by Chronic Obstructive Pulmonary Disease (COPD) and moderate to severe asthma.

Indacaterol works by stimulating adrenergic beta-2 receptors in the smooth muscle of the airways. This causes relaxation of the muscle, thereby increasing the diameter of the airways, which become constricted in asthma and COPD.

At the recent SEC meeting for Pulmonary held on 5th December 2023, the expert panel reviewed the proposal along with the BE protocol and justification for CT waiver of the FDC Glycopyrrolate plus Indacaterol Maleate Metered dose inhalation presented by drug major Zydus Healthcare.

After detailed deliberation, the committee recommended that the firm should conduct a BE study.

In addition, the expert panel stated, “Clinical trial waiver was not considered at this stage.”

Following the above the committee suggested to the firm that the result of the BE study should be presented before the committee for review.

Also Read: Modify phase III clinical trial protocol: CDSCO panel tells Akum Pharma on antidiabetic FDC

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Merck gets European Commission nod for two new indications for Keytruda in gastrointestinal cancers

Rahway: Merck, known as MSD outside of the United States and Canada, has announced the European Commission (EC) has approved two new indications for KEYTRUDA, Merck’s anti-PD-1 therapy, in gastrointestinal cancers:

  • KEYTRUDA in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1 with a Combined Positive Score (CPS) ≥1;
  • KEYTRUDA in combination with gemcitabine and cisplatin for the first-line treatment of locally advanced unresectable or metastatic biliary tract carcinoma (BTC) in adults.

These approvals by the EC follow positive recommendations from the Committee for Medicinal Products for Human Use received in October 2023 and November 2023 and were based on overall survival (OS) results from the Phase 3 KEYNOTE-859 and KEYNOTE-966 trials, respectively.

In KEYNOTE-859, KEYTRUDA plus chemotherapy significantly improved OS in the overall patient population, reducing the risk of death by 22% (HR=0.78 [95% CI, 0.70-0.87]; p<0.0001) compared to chemotherapy alone at a median follow-up of 12.0 months (range, 0.1 to 45.9 months). In patients whose tumors expressed PD-L1 (CPS ≥1), KEYTRUDA plus chemotherapy reduced the risk of death by 26% (HR=0.74 [95% CI, 0.65-0.84]; p<0.0001). Median OS was 13.0 months (95% CI, 11.6-14.2) for patients treated with KEYTRUDA plus chemotherapy vs 11.4 months (95% CI, 10.5-12.0) for chemotherapy alone. In the study, approximately 80% of patients had tumors which expressed PD-L1 (CPS ≥1).

In KEYNOTE-966, KEYTRUDA plus chemotherapy demonstrated a statistically significant improvement in OS, reducing the risk of death by 17% (HR=0.83 [95% CI, 0.72-0.95]; one-sided p=0.0034) compared to chemotherapy alone at the trial’s pre-specified final analysis for OS. Median OS was 12.7 months (95% CI, 11.5-13.6) for KEYTRUDA plus chemotherapy versus 10.9 months (95% CI, 9.9-11.6) for chemotherapy alone.

“KEYTRUDA has shown its potential as an important treatment option in the EU across a number of gastrointestinal cancers, with seven indications based on data from our extensive clinical development program,” said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. “With these two new approvals of KEYTRUDA-based regimens in advanced HER2-negative gastric and gastroesophageal junction cancer and advanced biliary tract cancer, Merck continues to demonstrate progress in providing treatment options to patients in Europe.”

The safety of KEYTRUDA plus chemotherapy has been evaluated in 4,787 patients across tumor types. In KEYNOTE-859, the incidence of Grade 3-5 adverse reactions in patients with gastric cancer was 75% for KEYTRUDA plus chemotherapy and 70% for chemotherapy. In KEYNOTE-966, the incidence of Grade 3-5 adverse reactions in patients with BTC was 85% for KEYTRUDA plus chemotherapy and 84% for chemotherapy alone.

These approvals allow marketing of these KEYTRUDA regimens for these indications in all 27 EU member states, as well as Iceland, Liechtenstein, Norway and Northern Ireland. With these decisions, KEYTRUDA is now approved for 26 indications in the EU, including seven in gastrointestinal cancers.

Merck has an extensive clinical development program evaluating KEYTRUDA in gastrointestinal cancers and is continuing to study KEYTRUDA for multiple uses in gastric, hepatobiliary, esophageal and colorectal cancers.

Read also: USFDA grants priority review to Merck investigational 21-valent Pneumococcal Conjugate Vaccine specifically designed to protect adults

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JIPMER General Surgery faculty, residents excel at ASICON 2023

Visakhapatnam: In a resounding display of excellence, the faculty and residents of the Department of Surgery of Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) garnered accolades at the 82nd Annual Conference of the Association of Surgeons of India (ASICON 2023), held in Visakhapatnam from 13th-16th December 2023.

The prestigious ASICON event served as a platform for showcasing cutting-edge advancements and fostering collaboration within the surgical community. The Department of Surgery’s representatives not only participated actively but also secured awards that underscore their commitment to innovation and skill in the field.
Also Read:UCMS Professor Dr Satendra Singh conferred National Annual Award for Medical Humanities 2023

Dr Vijaykumar C, Associate Professor received the Best Faculty Paper award (Second Prize) for the paper entitled “Telescopic dissection vs. Balloon dissection during laparoscopic TEP inguinal hernia repair- A double-blinded Randomized Control Trail”. The paper was co-authored by Varun R, Balasubramanian G, Uday Shamrao Kumbhar.

Dr Likhita Subhash Singh, Senior resident received the Best Paper award (First Prize) in the free paper category for the paper titled ” Comparison of Adapted Enhanced Recovery After Surgery (ERAS) Pathway versus standard care in patients undergoing emergency abdominal surgery- A Randomized Controlled Trial”. The paper was co-authored by Gurushankari B, Sureshkumar S, Anandhi A, Mahalakshmy T, Pankaj Kundra, and Vikram Kate. 

Dr Debolina Pal, Junior resident, received the Dr C Palanivelu Best Postgraduate Paper Award (First Prize) for the paper titled “Assessment of behavioural preparation for surgery in patients undergoing emergency abdominal surgeries and its effect on recovery outcome”. The paper was co-authored by Ashita Geli, Vishwanath, Mahalakshmy T, Vikram Kate.

Dr Bhanu Prakash, Junior resident, received the Dr. C Palanivelu Best Postgraduate Paper award (Second Prize) for the paper titled “Prognostic nutritional index as a predictor of postoperative outcome in gastrointestinal malignancies”. The paper was co-authored by Udayanilandan, Suresh C, Reddy Abhinaya, Ankit Jain, Uday Shamrao Kumbhar, and Rajeswari M.

Dr Dripta Ramya Sahoo, Junior resident, received the Best State Chapter award (Second Prize) for the paper titled “Effectiveness of low molecular weight heparin in reduction of severity of inflammation in patients with acute pancreatitis – a randomised control trial”. The paper was co-authored by Vedaprakash, Elamurugan TP, Nanda Kishore Maroju, and Ramkumar G. 

Also Read: Surgeons Raghu Ram, Dr K Pattabhiramaiah get ASI lifetime achievement awards

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Pradhan Mantri Bhartiya Janaushadhi Pariyojana achieves target of Rs 1000 crore in sales in FY 2023-24

New Delhi: Pradhan Mantri Bhartiya Janaushadhi Pariyojana (PMBJP) has created another landmark in the history of generic medicines in the country by selling medicines worth Rs. 1000 Crore this year. This achievement was made possible only by the people of the country, who have saved approximately 5000 crores by purchasing medicines from Jan Aushadhi Kendras which is present in more than 785 districts of the country. This substantial growth is a testament to PMBI’s commitment to serving more communities and reaching a broader audience.

In last 9 years, there has been more than 100 times growth in number of Kendras which were only 80 in 2014 and have now grown to almost 10000 Kendras covering almost all the districts of the country. Hon’ble Prime Minister in his Independence Day speech, 2023 has announced for opening of 25,000 Pradhan Mantri Bhartiya Janaushadhi Kendras (PMBJKs) across the country.

The Prime Minister virtually launched the 10,000th Janaushadhi Kendra at AIIMS, Deoghar, Jharkhand on 30th November, 2023 and further paved the way for expanding the number of Kendras to 25,000 for wider outreach and easy accessibility of medicines to the people of the country.

Accordingly, the Government has set a target to open 25,000 Janaushadhi Kendras across the country by March, 2026. Keeping up the promise, online applications have been called for opening of new Janaushadhi Kendras across all districts of the nation through the official website of PMBI.

Under this scheme, there are more than 10,000 functional Janaushadhi Kendras across the country. The product basket of PMBJP comprises 1963 medicines and 293 surgical devices covering all major therapeutic groups such as Cardiovascular, Anti-cancers, Anit-diabetics, Anti-infectives, Anti-allergic, Gastro-intestinal medicines, Nutraceuticals, etc. There are five warehouses at Gurugram, Bengaluru, Chennai, Guwahati and Surat. These are backed by SAP based inventory management system. Further, 36 distributors are functional across the country to support the supply of medicines to remote and rural areas. PMBJP has further added number of Ayurvedic products in its product basket for immunity boosting and it is easily available at affordable prices for people.

Read also: Jan Aushadhi scheme has led to savings of Rs 7416 cr for citizens this fiscal: Govt

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Use of Eplerenone potential strategy to reduce arterial inflammation among persons with HIV: JAMA

USA: Eplerenone was shown to significantly reduce arterial inflammation in a 12-month, placebo-controlled, randomized clinical trial of 26 well-treated persons with HIV (PWH) without known cardiovascular diseases (CVD). The researchers observed an even greater effect in the most diseased segment of the index vessel.

“Mineralocorticoid receptor antagonism by Eplerenone may be a potential strategy to reduce arterial inflammation in HIV patients,” the researchers wrote in their study published in JAMA Cardiology.

People with HIV are 1.5 to 2 times more likely to be affected by cardiovascular disease. This increased burden of heart disease may be driven by Chronic systemic and local inflammation that persists among PWH taking antiretroviral therapy (ART).

Previous studies have shown increased renin-angiotensin-aldosterone system (RAAS) activation among HIV patients in association with increased markers of arterial inflammation. Therefore, RAAS activation may be a potential novel target for CVD prevention in HIV.

In the MIRACLE HIV trial, Eplerenone improved myocardial perfusion indices. In the MIRABELLA HIV substudy of MIRACLE HIV, Suman Srinivasa, Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues hypothesized that RAAS blockade using mineralocorticoid receptor antagonism would reduce arterial inflammation among HIV patients assessed by 18F-fludeoxyglucose–positron emission tomography/computed tomography (18F-FDG PET/CT).

They aimed to investigate the effects of eplerenone on arterial inflammation among well-treated PWH without known CVD. Participants were enrolled in the MIRABELLA study and underwent additional 18F-FDG PET/CT imaging of the aorta and carotid arteries to assess arterial inflammation over 12 months of treatment with eplerenone vs placebo.

The study’s main outcome was a change in the target-to-background ratio (TBR), a measure of arterial wall inflammation, following 12 months of treatment. The index vessel was defined as the vessel (left carotid artery, aorta, or right carotid artery) with the highest TBR at baseline in each participant.

Twenty-six participants (mean age, 54 years; 69% males) were randomized to Eplerenone, 50 mg, twice a day (n=13) versus identical placebo (n=13). Treatment groups were of similar age, body mass index, and sex.

The study led to the following findings:

  • Eplerenone was associated with a reduction in TBR of the primary endpoint, the index vessel (eplerenone vs placebo: model treatment effect, −0.31; percentage change, −12.4% versus 5.1%).
  • There was a significant reduction of the TBR of the index vessel’s most diseased segment (MDS) (eplerenone vs placebo: −19.1% versus 6.8%).
  • A similar result was seen assessing the index vessel of the carotids (eplerenone vs placebo: −10.0% versus 9.7%).
  • Reduction in the TBR of MDS of the index vessel on 18F-FDG PET/CT correlated with improvement in the stress myocardial blood flow on cardiac magnetic resonance imaging (Spearman ρ = −0.67).

“The findings showed that eplerenone was associated with reduced arterial inflammation among well-treated PWH without known CVD,” the researchers wrote. They added, “Reductions in arterial inflammation as measured by 18F-FDG PET/CT were related to improvements in stress myocardial perfusion.”

‘Further larger studies should explore whether eplerenone is a potential treatment strategy for inflammatory-mediated CVD in persons with HIV,” they concluded.

Reference:

Srinivasa S, Abohashem S, Walpert AR, et al. Mineralocorticoid Receptor Antagonism by Eplerenone and Arterial Inflammation in HIV: The MIRABELLA HIV Study. JAMA Cardiol. Published online December 13, 2023. doi:10.1001/jamacardio.2023.4578

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Gluconolactone with multiple skin benefits ideal for use in cosmetic and dermatologic procedures

Poland: A recent study published in the Journal of Cosmetic Dermatology has shown a significant impact of gluconolactone (GLA) chemical peel treatment on lowering skin pH and transepidermal water loss (TEWL). GLA was also observed to have seboregulatory properties.

“GLA chemical peel treatment significantly lowered skin pH at all measurement points. Also, there was a significant reduction in TEWL around eyes, right cheek, and left forehead after GLA treatment,” the researchers reported. “No significant differences were observed between different GLA concentrations.”

The skin is a barrier to potentially harmful external factors, with a particular focus on protection against infection and water loss. The barrier’s quality can be assessed using objective instrumental measurements that determine skin parameters such as pH, transepidermal water loss, sebum level, and hydration. Barrier disorders are affected by the use of irritants, chemicals, excessive degreasing (which can affect TEWL increase), internal factors, hormonal disorders, allergies, dermatological diseases, and dietary deficiencies.

Gluconolactone is an oxidized glucose lactone derivative. In nature, GLA is found in cheese, honey, wine, tofu, and fruit juices. GLA exhibits moisturizing and antioxidant effects. It also presents soothing effects, improves the function of the skin barrier, and protects elastin fibres from UV-induced degradation.

Sylwia Jarząbek-Perz, Medical University of Lódź, Lódź, Poland, and colleagues, therefore, aimed to evaluate skin parameters such as transepidermal water loss, pH, sebum levels before, during, and after a series of applications of 10% and 30% GLA chemical peel in a split-face model.

The study included 15 female subjects. Three split-face procedures were conducted using two GLA solution concentrations applied on two sides of the face. The skin parameters were measured before treatments and 7 days after the last procedure at four measurement sites on either side of the face, that is, on the forehead, on the cheek, around the eye, and on the nose wing.

The study led to the following findings:

  • Measurement of sebum demonstrated some statistically significant changes between sebum levels in the cheeks after a series of treatments.
  • The pH measurement showed a reduction in pH value after each treatment at all measurement points.
  • The level of TEWL after treatments was significantly lower around the eyes, on the left forehead, and on the right cheek.
  • There were no significant differences between the use of different concentrations of the GLA solution.

“The findings reveal the multiple skin benefits of gluconolactone, making it an ideal ingredient for use in cosmetology, cosmetic, and dermatologic procedures,” the researchers concluded.

Reference:

Jarząbek-Perz, S., Dziedzic, M., Rotsztejn, H., & Kołodziejczak, A. (2023). Evaluation of the effects of 10% and 30% gluconolactone chemical peel on sebum, pH, and TEWL. Journal of Cosmetic Dermatology, 22(12), 3305-3312. https://doi.org/10.1111/jocd.15864

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Benidipine calcium channel blocker may reduce cigarette smoke-induced senescent cells and improves emphysema

France: In a recent study published in Aging, the researchers performed a chemical screen, using an FDA-approved drug library, to identify compounds selectively promoting the death of CS-induced senescent lung cells. 

In the study, researchers Alberta Palazzo, and colleagues from France revealed that benidipine calcium channel blocker promotes the death of cigarette smoke-induced senescent cells and improves lung emphysema.

Smoking is the main risk factor for many lung diseases including chronic obstructive pulmonary disease. Cigarette smoke (CS) contains carcinogenic and reactive oxygen species that favor DNA mutations and perturb the homeostasis and environment of cells. CS induces lung cell senescence resulting in a stable proliferation arrest and a senescence-associated secretory phenotype. It was recently reported that senescent cell accumulation promotes several lung diseases.

“Here, our aim was to identify senolytic compounds in the context of CS-induced senescence and to assess whether they improved lung emphysema.”

Aside from the well-known senolytic, ABT-263, the researchers identified other potentially new senescence-eliminating compounds, including a new class of molecules, the dihydropyridine family of calcium voltage-gated channel (CaV) blockers. Among these blockers, Benidipine decreased senescent lung cells and ameliorates lung emphysema in a mouse model. The dihydropyridine family of CaV blockers thus constitutes a new class of senolytics that could improve lung diseases.

“Hence, our work paves the way for further studies on the senolytic activity of CaV blockers in different senescence contexts and age-related diseases.”

Reference:

Palazzo A, Makulyte G, Goerhig D, Médard J, Gros V, Trottein F, Adnot S, Vindrieux D, Flaman J, Bernard D. Benidipine calcium channel blocker promotes the death of cigarette smoke-induced senescent cells and improves lung emphysema. Aging (Albany NY). 2023 Dec 12; 15:13581-13592 . https://doi.org/10.18632/aging.205259

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