Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech Health El Paso.

Elizabeth: Rick, here we are in the fall. We’re just post-Labor Day, so I’d like to turn first to JAMA because it’s getting to be that vaccine season. I, at least, am thinking pretty hard about the flu vaccine and the new COVID vaccine.

The AMA [American Medical Association] has stepped into this space because there’s been so much tumult surrounding the long-standing CDC’s Advisory Committee on Immunization Practices (ACIP) that they have established something else that’s called the Vaccine Integrity Project. And that’s based at the University of Minnesota’s Center for Infectious Disease Research and Policy. They feel that it’s necessary for medical societies at large to step into this space and to help to provide a trusted voice when it comes to what you really need to be doing about vaccines.

What this group did was take a look at the information that’s out there right now relative to COVID vaccines, flu vaccines, and RSV vaccines. How efficacious are they? Who are the groups that benefit? What’s the constellation of side effects that we’ve seen in various groups? And what are the recommendations relative to receiving vaccines?

So let’s take a look first at the COVID information. They surveyed 155 publications and demonstrated that, sure enough, getting the vaccine is associated with reduced risk of severe disease, medical encounters, and death among multiple age and risk groups. The vaccine efficacy, or VE, for the COVID-19 vaccine, based just on last year’s data, ranged from just about 20% to 55% against COVID-related hospitalization for all adults 18 years and older compared with unvaccinated individuals or those without a current season vaccine. Maternal vaccination, 60% reduction in COVID-related medical encounters during pregnancy, and also a reduction of those hospital encounters for infants throughout their first year of life. Adverse events of special interest: They have consistent safety profiles that are observed and are in favor, of course, of COVID vaccine receipt.

The influenza vaccine, 69 publications, once again a vaccine efficacy of 19% to 43%, reducing mortality by 30% to almost 66%. Reduction in hospitalizations across all age groups. Interestingly, one study reporting that vaccination during pregnancy reduced the risk of symptomatic disease among infants by over 44%.

And then the RSV data, once again, showing that people at both ends of the age spectrum — older people whose immunity is declining and very young infants — benefit from that. And this maternal vaccination reduced infant RSV-related hospitalization with efficacy from 51% to 70%. And also they noted that there’s an antibody that can be administered to children who are exposed. Applause then for the AMA, for the establishment of this committee, and for attempting to step into this space where there’s trusted information that can get out there.

Rick: Yeah. The Vaccine Integrity Project is fairly recent. I mean, it was just established in 2025 in response to concerns about the integrity of the U.S. vaccine policy. They focus on three prime areas of work. First, to respond to inaccurate or misleading information relating to vaccines. Secondly, to develop and disseminate evidence. Then thirdly, it’s fostered collaborations among different medical societies and public health organizations and other stakeholders because they realized it was important to develop that collaboration. Kudos to the American Medical Association for providing trustworthy, evidence-based data regarding vaccines and their use in the population.

Elizabeth: So, get vaccinated.

Rick: Great advice.

Elizabeth: Which would you like to turn to of yours?

Rick: Let’s talk about the gene-silencing therapy for a specific cardiomyopathy, what’s called transthyretin amyloid cardiomyopathy. It’s clear that there’s an increasing cause of damage to heart muscle not due to coronary artery disease. There are misfolded proteins that accumulate in the heart — these are amyloid proteins — that cause heart failure. And it’s particularly in older individuals. We have very good ways of diagnosing it now with specific imaging.

What therapies are available? Stabilizing therapy, and that is, it takes the protein and it stabilizes it so it doesn’t misform and deposit in the heart. The second is gene silencing, and let’s prevent production of the protein altogether. And this article is an analysis of gene-silencing therapy. And then also, what do we know about combining the two together?

These investigators looked at two specific studies that included over 2,000 patients that had the transthyretin amyloid cardiomyopathy. The gene-silencing therapy reduced the primary endpoint, all-cause mortality and recurrent cardiovascular events, a decrease of them by about 20%. It also improved symptoms and the 6-minute walk distance. There was no significant incremental benefit when people were taking this protein-stabilizing therapy. Adding gene-silencing therapy didn’t appear to be beneficial. The recommendation is to try either one of the two, but there doesn’t appear to be any benefit in combining them. Now, having said that, Elizabeth, there’s an ongoing trial to specifically test that hypothesis.

Elizabeth: So if we have identified this putative gene, why is it that silencing it only results in a 20% reduction in the complications of this condition?

Rick: Well, that’s a great question. I suspect a lot of it is because we don’t discover it until it’s in its more advanced forms. It’s already deposited in the heart, and it doesn’t remove that.

Elizabeth: And so does this suggest then that we ought to be screening people for this? This is pretty rare. I mean, I think I’ve only seen one case.

Rick: Well, it’s interesting, Elizabeth. Because when I was training, I would have said it’s rare as well, and I had a handful of patients. What happens is we didn’t do a very good job of looking for it because we didn’t have the best diagnostic tools, and those have both improved. As a result, it’s now a major cause of morbidity and mortality in cardiomyopathy in older individuals.

Elizabeth: OK. And that begs the question of screening then.

Rick: There is no good screening available and the incidence is fairly rare in the overall population. I do agree with you that we need the earlier detection or earlier suspicion to lead to earlier therapy.

Elizabeth: Moving target, it sounds like.

Let’s turn from here to Nature Medicine, something that could end up being really good news. It’s the identification of a protein that may be a first-trimester predictor of preeclampsia and fetal growth restriction.

This study takes a look at this really big group of women who agreed to be a part of a study to screen for proteins that might be involved with both of these conditions. This is the Pregnancy Outcome Prediction Study. They screened blood samples from thousands of women. Also, they looked at thousands of proteins. They identified this thing that’s called isthmin 2. Out of 2,904 proteins that they screened, they found it in the first trimester of pregnancy as the predictor, this low level of this for preeclampsia or fetal growth restriction. They validated that association in two independent cohorts, and those are the Pregnancy Outcome Prediction Study 2 and Improving Maternal Pregnancy And Child ouTcomes study. They find that we are seeing that there’s low levels. They find that this protein and mRNA, because they’re almost exclusively produced in the placenta and within the placenta, then they’re both associated with what’s called impaired invasion of the uterus by extravillous trophoblasts.

I learned something interesting in this paper, which is that humans have the deepest trophoblast invasion of any placental mammal. It’s so fascinating to me that humans… we’re not the biggest mammals out there, so why is it that we have this deepest invasion? This protein is involved in that whole process. If you’re able to identify this in the first trimester, that suggests that there might be some interventions that would be possible.

Rick: For our listeners that may not be aware, the trophoblast is the outer layer cells in the very early embryo and it forms the placenta. It actually anchors the embryo to the uterus and it produces key hormones to sustain pregnancy. This protein appears to be important in regulating trophoblast growth and development. When women have incomplete trophoblast invasion into the uterus, it affects vascular supply to the embryo, it affects hormones, and it predisposes to preeclampsia. So this particular protein is important in regulating that. Well, it may help with the diagnosis. More importantly, it can help with the therapy.

Elizabeth: Clearly, that’s going to be something that’s going to have to be developed, and right now the authors admit that there aren’t any therapeutic interventions that would enhance the secretion of this particular protein. They also say that this current study does not shed light on why there are lower levels in some women versus other women.

Rick: No. But as you mentioned, it’s a new protein, a new discovery, a pathway that hasn’t been particularly identified before. So, I look forward to more information about this in the future.

Elizabeth: I agree. So, let’s turn to the New England Journal.

Rick: I teed this up as a new therapy for COPD exacerbations. Now, COPD, or chronic obstructive pulmonary disease, remains a leading cause of death worldwide, and the prevalence — primarily because of continued cigarette smoking — is projected to reach approximately 600 million individuals by 2050. When people have COPD exacerbations, it accelerates a decline in their lung function. It impairs their quality of life. It increases their risk of further exacerbations and death.

Now, we have standard of care measures, which we know are effective in many, but not all. Currently, extending additional therapy depends upon identifying people that have high eosinophil counts as well. That eliminates a fair number of individuals. What you’d like to do is develop another additional therapy for people that have moderate or severe exacerbations despite standard-of-care therapy.

These investigators have looked at tozorakimab, which is a protein involved in inflammation, and it’s also involved in secretions. And it’s been shown in phase I and phase II trials to be beneficial. This is a phase III trial, where individuals received a weekly injection or placebo, in addition to standard therapy, to see how it affected moderate or severe exacerbations of their COPD.

And what they discovered is when it was used as an add-on therapy to standard inhalation therapy, it lowered the risk of moderate or severe exacerbations by about 30%. It didn’t depend upon identifying individuals with a high eosinophil count, so it could be applied to the greater population. There really weren’t any significant side effects, other than some irritation of the site of injection. This is really good news.

Elizabeth: It is good news, and I’m wondering how expensive this might be.

Rick: I don’t know the answer to that, but obviously, at some point, we need to do a cost-benefit analysis. When people have moderate or severe exacerbations, they present to the emergency department or are hospitalized in the ICU [intensive care unit]. There’s cost associated with that. And the question is, how expensive is the medication, and overall, is it beneficial in terms of reducing cost?

Elizabeth: And, of course, it wouldn’t be me without editorializing that the first thing we all need to do is quit smoking cigarettes.

Rick: Yep.

Elizabeth: On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.

for informational purposes only. We do not claim ownership, accuracy, or liability for the content provided. All rights belong to the original publisher.

The Digital Solution Centre

The Digital Solution Centre

Predicting Preeclampsia With a Protein? Gene-Silencing for Cardiomyopathy

Like this:

Related

Share this:

Like this:

Related