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Category: biotech/medical – Page 82

Frontline Osimertinib Combo Prolongs Survival in Advanced EGFR+ NSCLC

Among patients with central nervous system (CNS) metastases at baseline, the 36-month OS rate was 57% (95% CI, 48%-66%) with osimertinib/chemotherapy and 40% (95% CI, 31%-49%) with osimertinib alone. The 36-month OS rates among patients without CNS metastases were 67% (95% CI, 59%-74%) vs 58% (95% CI, 50%-65%) in each respective arm. Additionally, the 36-month rates were 54% (95% CI, 44%-63%) vs 42% (95% CI, 32%-51%) among patients with EGFR L858R mutations and 69% (95% CI, 61%-75%) vs 57% (95% CI, 49%-64%) among those with EGFR exon 19 deletions.

When considering patients who discontinued frontline osimertinib following disease progression, 69% (n = 88/127) of patients in the combination therapy arm and 77% (n = 143/185) in the monotherapy arm received subsequent therapy. The most common types of first subsequent therapy in the combination arm included platinum-based chemotherapy (44%) and non–platinum-based chemotherapy (30%). Among patients who received osimertinib monotherapy, the most common kind of subsequent treatment was platinum-containing chemotherapy (72%).

“The combination therapy used in this trial was associated with a higher incidence of grade 3 or higher adverse events and of [AEs] leading to the discontinuation of treatment than osimertinib monotherapy. Most high-grade toxic effects associated with the combination therapy were related to myelosuppressive effects, which are generally dose-related and reversible, with supportive interventions available to ameliorate such effects,” lead study author Pasi A. Jänne, MD, PhD, senior vice president of Translational Medicine and professor in the Department of Medical Oncology at Lowe Center for Thoracic Oncology of Dana–Farber Cancer Institute, wrote with coauthors in the publication.1 “Results from this trial provide evidence that first-line treatment with osimertinib plus platinum/pemetrexed led to significantly longer [OS] than osimertinib monotherapy among patients with EGFR-mutated advanced NSCLC.”

Metformin hijacks AMPK-ERK1/2 signaling to trigger a pathogenic “selection trap” and thymic atrophy

Qin et al. reveal that the diabetes drug metformin sets a “selection trap” in the thymus. It pushes developing immune cells toward maturation while simultaneously triggering their apoptosis via a metabolic stress-induced pathway, challenging the drug’s safety in non-diabetic contexts.

Dual therapy shows promise for childhood brain cancer

Researchers at the Children’s Cancer Institute and UNSW Sydney have tested a new way of treating childhood brain cancer by combining two medicines in lab studies. They found using the two treatments together may work better than using either on its own. The research is published in the journal Science Translational Medicine.

In the new study, Children’s Cancer Institute and UNSW Sydney researchers lab-tested a combined therapy approach on a group of difficult-to-treat brain tumors: diffuse midline gliomas (DMG). This group includes diffuse intrinsic pontine glioma (DIPG), a rare but fatal childhood brain cancer. Children diagnosed with DIPG usually survive for about 12 months.

UNSW Conjoint Professor David Ziegler and UNSW Conjoint Associate Professor Maria Tsoli led the study. They have been working for many years to find better treatments for DIPG.

Clinical features, pedigrees, MRI, and liver pathology of patients carrying heterozygous p.Glu230Lys

This Research Letter describes a new molecular basis for lipodystrophy syndromes.

Abhimanyu Garg & team report on a variant in ACAA2 that causes hepatitis and hypoglycemia during infancy and lipodystrophy during adulthood accompanied by elevated plasma long chain acylcarnitines.

Address correspondence to: Abhimanyu Garg, 5,323 Harry Hines Boulevard, Dallas, Texas 75,390, USA. Phone: 214.648.2895; Email: [email protected].

Find articles by Simha, V. in: | Google Scholar

1Mayo Clinic, Rochester, Minnesota, USA.

Abstract: Fanning the flames: IFN-γ fuels CAR-T inflammation and cytopenia:

A Commentary by Stefanie R. Bailey & Marcela V. Maus on Payal Goala et al.: https://doi.org/10.1172/JCI194631

1Division of Pediatric Hematology/Oncology, Department of Pediatrics, Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.

2Cellular Immunotherapy Program, Mass General Cancer Center, Krantz Family Center for Cancer Research, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, Masschusetts, USA.

Address correspondence to: Marcela V. Maus, 149 13th Street, Room 3.216, Charlestown, Massachusetts, 2,129, USA. Email: [email protected].

A Hidden Brain Signal Can Predict Alzheimer’s Years Before Diagnosis

A subtle change in brain wave activity could predict Alzheimer’s disease more than two years before diagnosis, according to a new study.

The signal could prove to be a sensitive biomarker of cognitive decline.

Using a noninvasive imaging technique called magnetoencephalography (MEG), neuroscientists at Brown University in the US and Spain’s Complutense University of Madrid and University of La Laguna analyzed the resting brain wave activity of 85 patients diagnosed with mild cognitive impairment.

Intervene Immune puts thymus regeneration back in the spotlight

This would be my first funding target if I had the money.

Beyond science, Brooke sees three main hurdles: regulation, manufacturing and physician usability. Public acceptance, he says, already appears strong. Regulatory pathways may be comparatively favorable, given the long histories of the cocktail’s components and existing approvals for immune deficiency states. Manufacturing is always a challenge for biologics at scale, but protein production is mature and scalable, and the company is building internal capacity.

The immediate obstacle, Brooke argues, is complexity. Intervene Immune is developing a dosing system designed to be relatively foolproof for doctors, and expects to build an AI assistant to support implementation as sufficient data accumulates.

Intervene Immune’s closing sentiment is less biotech slogan and more biological provocation. “No matter how old you may be, your body still remembers how to be young,” Brooke says.

Demographics, Services, and Practices in ADHD Coaching in the US

Survey: Online ADHD coaching has increased substantially since the pandemic, mostly by lay adults reporting lived experience with ADHD, as a rising alternative to formal ADHD care.

This survey study found that most ADHD coaches primarily operated outside the US health care system and reported workforce entry after the COVID-19 pandemic’s onset. Our findings suggest ADHD coaching is usually delivered through a 1:1 virtual format using a traditional outpatient psychotherapy model (weekly 1-hour sessions) and reached prospective clients through a combination of online marketing and health care referrals. ADHD coaches tended to be individuals without formal mental health training who self-identified as having ADHD (or a loved one with ADHD), may have received ADHD coaching themselves, and based practices on lived experiences. Unlike most licensed mental health clinicians, ADHD coaches practiced across state and international borders.

As expected, we detected a spike in ADHD coaching workforce entry at the COVID-19 pandemic’s outset that mirrored similar ADHD medication prescribing patterns.6 Herein, we reveal that intervention content self-reported by ADHD coaches is similar to those manualized in evidence-based CBTs for ADHD.37 The potential redundancy in content between ADHD coaching and CBT for ADHD could make it difficult for prospective clients and some medical clinicians to differentiate between these approaches. However, the aforementioned aspects of ADHD coaching are different than traditional CBTs in that ADHD coaching appears longer term, involves sharing lived experiences with ADHD, and offers support between sessions (Table 2).38-40 These features may make ADHD coaching especially palatable to adults with ADHD, who reportedly criticize routine care CBT as being too rigid, generic, and short term, with therapists who are stigmatizing, negativistic about ADHD, and unempathetic.

High-dose birth control pills linked to elevated fear in safe contexts

A new study published in Neuropsychopharmacology suggests that the use of oral contraceptives may influence how the brain regulates fear responses in safe environments. The research indicates that women who use birth control pills, particularly those with higher doses of synthetic estrogen, may experience elevated fear in safe contexts compared to women who have never used hormonal contraception. The findings also imply that these alterations in fear processing could persist for a significant period after an individual stops taking the medication.

Anxiety disorders and post-traumatic stress disorder are nearly twice as prevalent in women as they are in men. Biological factors likely contribute to this disparity, with sex hormones acting as potential mediators. Specifically, the hormone estradiol plays a significant role in how the brain manages fear and memory.

Effective fear regulation requires the ability to distinguish between a threat and a safety signal based on the surrounding environment. For example, seeing a snake in a forest might require a fear response, while seeing a snake in a zoo enclosure should not. This process is known as contextual fear regulation.

Neuroscientists link a common inflammatory molecule to the dopaminergic mechanisms of addiction

Treatments for autoimmune disorders might offer hope for methamphetamine addiction. Research published in Science Signaling indicates that blocking a specific immune protein dampens the drug’s effect on the brain’s reward centers.

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