Innovative Therapies: Secukinumab for Polymyalgia Rheumatica and Gene Editing for Hypercholesterolemia

This week’s topics include a genetic treatment for hypercholesterolemia, cannabis and hyperemesis, reducing the risk of dementia, and a newer anti-inflammatory for polymyalgia rheumatica treatment (PMR).

Program notes:

0:38 – Overview of Polymyalgia Rheumatica treatment

1:35 – Explanation of the interleukin‑17A‑targeting antibody

2:35 – Remission observed at 12 weeks and sustained through 52 weeks

3:11 – Cannabis‑induced hyperemesis syndrome

4:11 – Emergency department visits linked to cannabis use

5:11 – Prior coding methodology did not capture these cases

6:05 – Gene inhibition of PCSK9

7:05 – Delivery via nanoparticle carrier

8:11 – Vascular risk factors and their impact on dementia

9:11 – Analyses stratified by age, sex, and APOE status

10:13 – Projected 13 additional dementia‑free years

11:58 – Podcast conclusion

Transcript:

Elizabeth: What are three strategies to prevent dementia?

Rick: Gene editing for individuals with high cholesterol.

Elizabeth: What are the health risks associated with heavy cannabis use?

Rick: And a newer anti‑inflammatory agent for an inflammatory disease.

Elizabeth: That’s the focus of this week’s TTHealthWatch episode, a weekly review of medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a medical journalist based in Baltimore.

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

Elizabeth: Rick, the previous statement was difficult to interpret, so I will refer directly to the New England Journal of Medicine for clarification.

Rick: Understood. I hope this sparks your interest, as this may be the first time in our more than 20 years of podcasting that we discuss this inflammatory condition—polymyalgia rheumatica. It is the second most common idiopathic inflammatory rheumatic disease after rheumatoid arthritis.

Elizabeth: PMR is widely discussed, especially in older adults. The temporal artery biopsy for giant cell arteritis is daunting. I’m curious about the durability of the response; how long did the study follow participants?

Rick: The trial spanned 52 weeks. Participants received treatment for 12 weeks, after which remission began at 12 weeks and persisted for an additional 40 weeks, indicating robust durability.

Elizabeth: What adverse effects were observed?

Rick: There was no difference between secukinumab and placebo. Common adverse events included nasopharyngitis, rare hypersensitivity reactions, urinary tract infections, and occasional fungal infections—generally mild.

Elizabeth: Do these side effects match those seen in other patient groups receiving this medication?

Rick: Yes, the profile is similar. The drug has been used in thousands of patients across various indications, and we are now applying it to this new condition.

Elizabeth: We appreciate the versatility of repurposing an existing therapy with a well‑established safety record.

We will now examine a report from the Morbidity and Mortality Weekly Report (MMWR) regarding trends in emergency department visits for cannabis‑associated hyperemesis syndrome, identified through a newly implemented diagnosis code.

Cannabis hyperemesis syndrome (CHS) presents with recurrent nausea and vomiting and is linked to frequent cannabis consumption. The CDC recently analyzed these trends following the introduction of a dedicated ICD‑10 code that became effective on October 1, 2025.

The analysis examined nationwide emergency department data for cannabis‑related visits complicated by hyperemesis. After the new coding scheme was applied, the incidence rose from 3.35 to 11.26 per 10,000 emergency department visits—a nearly fourfold increase.

These visits were disproportionately observed in individuals aged 15‑24 and among females, with notable increases in certain demographic groups after the code change. Although the syndrome is genuine and likely under‑recognized, I remain skeptical that the surge reflects true epidemiology, as it appears driven primarily by the revised coding methodology.

Previously, coding relied on separate entries for vomiting and cannabis use, often leading to missed cases. The updated code specifically captures prolonged cannabis‑induced hyperemesis, thereby increasing reported cases. This change likely serves to raise physician awareness of the condition.

Indeed, cannabis products have evolved rapidly, and recent evidence suggests that symptom onset may occur much earlier than previously thought, sometimes within the first year of use.

Hyperemesis does not appear to correlate with cannabis potency, but it does correlate with duration and frequency of use; many current cases involve less frequent consumption.

We will now return to the New England Journal of Medicine.

Over the past five years, we have extensively discussed PCSK9 inhibitors for treating hypercholesterolemia. Individuals with elevated PCSK9 levels exhibit markedly high cholesterol; inhibiting PCSK9 enhances LDL receptor expression, reduces cholesterol, and lowers cardiovascular risk. Three FDA‑approved injectable formulations exist, and an oral inhibitor is now available. Ideally, we could eliminate PCSK9 production altogether by modifying the gene itself.

This study presents a phase I trial involving 35 participants with hypercholesterolemia who remained uncontrolled on statins or other lipid‑lowering therapies. Participants were randomized to receive placebo or escalating doses of a gene‑editing approach that disables PCSK9 expression. The therapeutic protein is packaged within a nanoparticle that targets the liver via a specific receptor, is internalized, and delivers the gene‑editing agent to the PCSK9 gene, where it introduces a nick to halt protein production.

LDL cholesterol decreased in a dose‑dependent manner, with high doses achieving 85‑90% reductions. The effect persisted for at least one year in 15 of the 35 participants, suggesting considerable durability.

It is intriguing to consider the broader physiological impacts of modulating gene function.

Animal studies demonstrated hepatic specificity and an absence of off‑target effects, alleviating safety concerns. Future trials will enroll larger cohorts over longer periods; if proven safe and durable, this approach could halve to three‑quarters the risk of myocardial infarction and stroke.

We will continue to monitor developments closely.

We will now examine a Neurology article that uses data from the Atherosclerosis Risk in Communities (ARIC) neurocognitive study to estimate dementia‑free survival from age 55 to 95, based on midlife vascular risk burden.

The cohort comprised individuals who were alive and dementia‑free at age 55 and had undergone a second assessment measuring diabetes, hypertension, and current smoking. Vascular risk burden was quantified as the number of these risk factors. Dementia was ascertained via cognitive testing, informant interviews, and ongoing surveillance through 2022. Analyses were stratified by sex, race, and apolipoprotein E genotype.

More than 12,000 participants with a median follow‑up of 26.3 years; over 3,000 developed dementia while more than 5,000 died without dementia. Compared with zero risk factors, having three risk factors was linked to nearly a threefold increase in dementia risk and a sixfold increase in mortality without dementia. Greater vascular burden correlated with reduced dementia‑free survival.

Women exhibited longer dementia‑free survival than men, and Black participants had shorter survival than White participants. The investigators concluded that optimal midlife vascular health could add nearly 13 years of dementia‑free life.

The report notes that roughly 42% of middle‑aged U.S. adults may develop dementia in their lifetime, and the risk rises substantially with advancing age, particularly beyond 90 years.

Thus concludes this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

I’m Rick Lange. Please listen and make healthy choices.

And begin early.

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