BackgroundTianwang Buxin Dan is a classical Traditional Chinese Medicine formula with documented clinical use in treating neuropsychiatric disorders, yet its molecular mechanisms remain incompletely understood.MethodsWe developed an integrated analytical framework combining transcriptomic and metabolomic profiling with deep learning to investigate the neurotransmitter metabolism regulatory mechanisms of Tianwang Buxin Dan. Data were collected from a para-chlorophenylalanine (PCPA)- induced insomnia rat model following formula intervention. A multi-omics feature fusion strategy incorporating autoencoder-based dimensionality reduction and cross-modal attention mechanisms was implemented to address data heterogeneity.ResultsA total of 1,847 differentially expressed genes and 286 differential metabolites were identified. The constructed deep neural network achieved 91.2% classification accuracy with an AUC of 0.956 in five-fold cross-validation, and permutation testing confirmed that performance was significantly above chance (p < 0.001). Ablation experiments demonstrated that integrated multiomics outperformed single-omics models. Tryptophan hydroxylase 2 (TPH2) upregulation and monoamine oxidase A (MAO-A) suppression were identified as key features and partially validated by qPCR and Western blot.DiscussionTianwang Buxin Dan may modulate neurotransmitter metabolism through coordinated regulation of biosynthetic and catabolic pathways. A component-target-pathway regulatory network identified 47 key molecular targets interconnected through 156 functional associations. This work provides a computational framework applicable to mechanism studies of other compound TCM formulations.
Power without limits: exploring emotional regulation, moral authority, and psychiatric overreach through the Wizarding World of Harry Potter
BackgroundPsychiatry has never had more tools to relieve psychological suffering. Psychopharmacology, neuromodulation, early intervention, digital monitoring, and preventive approaches have expanded what clinicians can do. Yet this growing technical capacity also raises an uneasy question: when does care become control? Cultural narratives can offer spaces for examining such tensions, particularly when they dramatize power, vulnerability, suffering, and moral authority.AimThis narrative review uses the Wizarding World of Harry Potter as a conceptual lens to examine emotional regulation, moral authority, and psychiatric overreach, focusing on two contrasting figures: Lord Voldemort and Isidora Morganach.MethodsA theory-informed narrative review was conducted using a concept-focused analytic framework and structured conceptual synthesis. Literature was identified through focused searches in PubMed, PsycINFO, Scopus, and Google Scholar from database inception to June 2026, complemented by backward reference tracking. Sources covered Harry Potter scholarship, emotional regulation, psychological flexibility, narcissism and Dark Triad traits, medicalization, overdiagnosis, clinical ethics, and narrative medicine. To improve transparency, the synthesis distinguished direct literature on the Wizarding World from indirect psychiatric, psychological, ethical, and medical humanities scholarship used for conceptual interpretation.ResultsTwo pathways to psychiatric overreach and an intermediate zone of proportionate care were identified. The first, represented by Voldemort, involves destructive domination, emotional suppression, denial of vulnerability, instrumental use of others, and coercive authority. The second, represented by Isidora Morganach, involves hyper-compassionate control, intolerance of suffering, elimination of negative affect, moral certainty, and paternalistic intervention. Between these extremes, the intermediate zone emphasizes emotional integration, psychological flexibility, shared decision-making, contextual judgment, ethical proportionality, and clinical humility. Although one pathway is cruel and the other compassionate, both illustrate power exercised without sufficient emotional integration or ethical restraint.ConclusionBy exploring psychiatric questions through the Wizarding World, this review highlights how narrative frameworks can clarify the ethical boundaries of intervention. The central lesson is not that intervention is dangerous, but that intervention must remain proportionate, reflective, and ethically bounded. Psychiatry’s task is not to abolish all distress, but to relieve suffering while preserving autonomy, meaning, and human vulnerability.
Oncology must confront hidden side effects
Nature Medicine, Published online: 08 July 2026; doi:10.1038/s41591-026-04554-9
As a new generation of cancer drugs continues to extend the lives of people with cancer, strategies for recording and managing their toxicity and long-term effects will need innovation too.
Another big premium hike on the horizon
Get your daily dose of health and medicine every weekday with STAT’s free newsletter Morning Rounds. Sign up here.
Good morning from your shriveled-up Fourth of July leftovers. On this day in 1776, the Declaration of Independence was read in public for the first time, in Philly’s Independence Square. It was subsequently published in newspapers throughout the no-longer-colonies, though not always on the front page (!).
Opinion: The AI licensure debate is missing the point of licensure
A cardiologist reviews an echocardiogram flagged by an algorithm she did not choose, trained on data she has never seen, deployed by a health system that did not ask for her input. The algorithm recommends a diagnosis. She disagrees. She overrides it. The patient does well.
No one will remember this moment. But if she had acquiesced and the patient suffered harm, she would be the one in the deposition, with her license on the line. Not the engineer who built the algorithm. Not the vendor who sold it. Not the health system that deployed it.
Are glucose monitors a good thing for 2-year-olds? Experts look at risks, benefits
You get a CGM, you get a CGM, everybody gets a CGM? For the first time in the United States, children 2 and older can also get a continuous glucose monitor without a doctor’s prescription.
Is that a good thing? The Food and Drug Administration thinks so.
Drug Candidate Shows Early Promise for Treating Alzheimer’s Damage
A drug candidate developed at King’s College London boosts DNA repair and reduces neuronal damage, as well as lowering neuroinflammation and could become a new treatment option for people with early stage Alzheimer’s disease in the future.
Writing in the journal FEBS Open Bio, lead author Jonathan Corcoran, PhD, a professor at King’s College London, and colleagues report results of a study carried out in a mouse model of Alzheimer’s disease that tested KCL-286, a retinoic acid receptor-beta agonist, and showed it had beneficial effects in the animals.
As Alzheimer’s disease develops, amyloid-beta accumulates and suppresses the brain’s natural retinoic acid signaling. This, as well as other factors, leaves neurons increasingly unable to repair DNA damage. The unrepaired damage then triggers microglial and astrocyte overactivation, which contributes to further neuronal injury in a self-reinforcing loop.
Mice treated with KCL-286 had significantly fewer DNA double-strand breaks in neurons than untreated mice, something seen in Alzheimer’s patients. They also had increased neuronal expression of BRCA1 protein, a DNA repair and tumor suppressor protein, suggesting KCL-286 partly works by ramping up the brain’s own repair machinery. In certain cancers, a BRCA1 mutation results in reduced or absent functional protein, which increases cancer risk over time.
KCL-286 also seemed to reduce inflammation in the brain of treated mice. Microglia and astrocytes were both abnormally enlarged and activated in the animals before treatment. However, after treatment the size and shape of these cells went back towards normal, in other words, calming dangerous inflammation without getting rid of the cells.
“We think of the drug as repairing potholes in a road—once the damage is fixed, normal traffic can flow again and the system settles down. By repairing the underlying damage, we can allow the system to reset,” said Corcoran in a press statement.
This is an early stage study and still needs to be tested in humans, but KCL-286 has already completed a Phase I trial in healthy human volunteers with no drug-related adverse events and is known to cross the blood-brain barrier efficiently. This is because the drug candidate is also being tested for treatment of spinal cord injury, hence the earlier Phase I study.
Both acute spinal cord injury and chronic neurodegeneration in Alzheimer’s involve accumulation of DNA double-strand breaks in neurons. In the former this is caused by the mechanical trauma and subsequent inflammation, whereas in the latter it builds up gradually over years.
The lack of side effects seen in the Phase I study is also important for KCL-286’s development as a possible Alzheimer’s treatment, as two earlier, non-selective retinoid drugs tested for treatment of Alzheimer’s caused side effects because they hit multiple off target receptor subtypes. KCL-286’s selectivity for the retinoic acid receptor-beta is designed to avoid this.
“Together with its favorable human safety profile, the data support further investigation of selective retinoic acid receptor-beta agonism as a therapeutic strategy for modifying pathogenic processes associated with Alzheimer’s disease,” conclude the authors.
The researchers think that if KCL-286 reaches the clinic early treatment is likely to be key to success. They also note there is potential for this type of therapy to be used in combination with approved Alzheimer’s treatments like lecanemab, which act to reduce harmful amyloid beta in the brain.
The post Drug Candidate Shows Early Promise for Treating Alzheimer’s Damage appeared first on Inside Precision Medicine.
Vertex Eyes Expansion Beyond Cystic Fibrosis with Planned $10B Crinetics Buyout
Vertex Pharmaceuticals has agreed to acquire Crinetics Pharmaceuticals for $10 billion cash, the companies said, in a deal that would expand the buyer’s rare disease portfolio beyond its anchor indication of cystic fibrosis (CF), by adding an approved treatment and a pipeline anchored by two Phase III candidates, all predicted to generate more than $5 billion in annual revenue.
Based in San Diego, Crinetics focuses on discovering, developing, and commercializing therapeutics for endocrine diseases. The company’s first marketed drug Palsonify® (paltusotine), an oral SST2 agonist, was approved by the FDA in September as the first and to date only once-daily oral therapy for adults with acromegaly, a debilitating condition which affects an estimated 20,000 Americans. Palsonify won European Commission approval in April and is under review by regulators elsewhere in the world.
Palsonify has enjoyed rapid uptake among acromegaly patients, with Crinetics reporting the drug generated net product revenue of $10.3 million during the first quarter, with 232 patients enrolling for treatment. Approximately 70% of patients treated with Palsonify at the end of Q1 were on reimbursed therapy—reflecting payers increasingly agreeing to cover the treatment, according to the company.
Within the first two quarters of its U.S. launch, Palsonify was prescribed by 263 unique healthcare providers.
Under its generic name paltusotine, the drug is in Phase III study for a second indication of carcinoid syndrome, a rare condition resulting from neuroendocrine tumors.
‘Excellent strategic fit’
“Crinetics is an excellent strategic fit for Vertex, with its focus on serious diseases in specialty markets with significant unmet need, well-understood causal human biology, and potentially best-in-class medicines that could deliver transformative benefit to patients,” Reshma Kewalramani, MD, Vertex’s CEO and president, said in a statement. “We believe Vertex can build on the strong momentum of the Palsonify launch by applying our experience in commercializing medicines for rare genetic diseases.”
Crinetics investors agreed, roaring their approval of the pending acquisition as the company’s shares all but doubled in early trading Tuesday, zooming 99% to $83.54 as of 10:28 am ET from yesterday’s closing price of $42.03. Vertex shares dipped 2% to $516.48 from $529.59 at Monday’s closing bell.
Also in late-stage development is Crinetics’ lead pipeline candidate atumelnant, an oral adrenocorticotropic hormone (ACTH) antagonist now under development for congenital adrenal hyperplasia (CAH) and ACTH-dependent Cushing’s syndrome.
In classic CAH, a rare chronic genetic disease with 17,000 addressable patients in the U.S., atumelnant is in a pair of clinical trials. One is a Phase III study in adults with the most common cause of the disease, 21-hydroxylase deficiency (21-OHD). The study’s estimated primary completion date is May 2027 (NCT07144163). The other trial is a Phase II/III study in children ages one to <18, which has an estimated primary completion date of March 2030 (NCT07159841).
Earlier Phase II studies of atumelnant showed that patients treated with the therapy achieved near normalization of excess androgen levels on physiologic replacement doses of glucocorticoids—a therapeutic profile that Crinetics has said positions atumelnant to become the leading treatment for people with CAH.
Atumelnant (formerly CRN04894) is also being developed for ACTH-dependent Cushing’s syndrome, and is under study in a Phase Ib/IIa open-label, multiple-ascending dose exploratory study (NCT05804669) designed to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamic biomarker responses associated with the treatment.
‘Significant potential’
“We are also excited by the significant potential of atumelnant to transform the treatment landscape for CAH, setting a new standard of care where patients do not have to choose between managing their excess adrenal androgens and enduring the side effects of high-dose steroids,” Kewalramani said.
One analyst said a Vertex buyout would be good news for Crinetics.
“This is a solid outcome for CRNX, given stock pressure from the near-term Palsonify launch (generally slow and steady launch but (+) [positive] progress by CRNX so far) and the fact that key Phase III catalyst for CAH isn’t until late 2027/28,” Jefferies equity analyst Dennis Ding wrote today in a research note.
In a regulatory filing yesterday, Crinetix shared an email it sent to employees, stating: “We have always been confident in the ability of Crinetics to achieve our plan and were not actively looking to sell the company when Vertex approached us. However, after careful consideration, our board unanimously determined that the transaction is in the best interests of our shareholders.”
Crinetics’ pipeline of more than 10 disclosed candidates includes:
- CRN09682, a Phase I nonpeptide drug conjugate candidate being developed to treat somatostatin receptor 2 (SST2) expressing neuroendocrine tumors and other SST2 expressing solid tumors.
- Discovery-phase preclinical programs focused on endocrine targets that include thyroid stimulating hormone (TSH), parathyroid hormone (PTH), somatostatin receptor 3 (SST3), growth hormone (GH), glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), as well as GPCR-targeted oncology indications.
Vertex said the deal was expected to contribute immediately to revenue growth via the ongoing launch of Palsonify, which the company says has blockbuster (greater than $1 billion in annual sales) potential in acromegaly. Longer term, Vertex says, atumelnant could also generate multiple billions of dollars in CAH, with additional revenue potential in Cushing’s syndrome.
$5B revenue forecast
At peak year, Palsonify and atumelnant could deliver more than $5 billion in combined annual revenue, Vertex said, and thus contribute toward its goal of delivering sustained double-digit revenue growth, plus industry leading operating margins. The transaction is expected to add to non-GAAP operating income as of 2029.
Jefferies analyst Ding commented that atumelnant in CAH is expected to generate the largest share of the projected $5 billion, as in $2 billion to $3 billion, plus another $1 billion to $2 billion for Cushing’s syndrome–with the remaining $1 billion to be generated by Palsonify in acromegaly.
Scotiabank analyst Louise Chen told Reuters: “The deal adds a fifth vertical, endocrinology, which helps diversify VRTX’s concentration in CF.”
That concentration has proven lucrative for Vertex: During Q1, CF treatments generated $2.915 billion in total revenues, 98% of the company’s total revenue of $2.987 billion.
Vertex has agreed to acquire all outstanding shares of Crinetics common stock for $85 per share cash, in a deal valued at $8.8 billion net of estimated cash acquired. Vertex said it expects to finance the acquisition using a combination of cash on hand and debt, supported by $4.5 billion of fully committed bridge financing from Bank of America and Morgan Stanley Senior Funding.
Vertex finished the first quarter with cash, cash equivalents, and total marketable securities of $13 billion, up from $12.3 billion as of December 31, 2025. The company attributed the increase primarily due to cash flows from operating activities, partially offset by repurchases of Vertex’s common stock.
The transaction is expected to close in the third quarter subject to customary closing conditions, including receipt of regulatory approvals and approval by Crinetics shareholders.
“Nearly 18 years ago, we founded Crinetics with a clear goal of transforming the lives of patients living with endocrine-related diseases. Today marks a historic milestone as we embark on this next chapter with Vertex,” stated R. Scott Struthers, PhD, Crinetics’ co-founder and CEO. “Vertex’s global infrastructure and commercial footprint will serve to amplify the reach of our science and allow us to maximize the impact of Palsonify, atumelnant and our pipeline.”
The post Vertex Eyes Expansion Beyond Cystic Fibrosis with Planned $10B Crinetics Buyout appeared first on GEN – Genetic Engineering and Biotechnology News.
New Clues to Inherited Heart Disease Point to Broader Role for Mavacamten
A targeted therapy already transforming treatment for hypertrophic cardiomyopathy (HCM) may be effective across a broader range of disease-causing genetic mutations than previously understood, according to new preclinical research published in Nature Cardiovascular Research.
The study identifies a previously unknown molecular mechanism underlying one of the most common inherited forms of HCM and demonstrates that the cardiac myosin inhibitor mavacamten—the first targeted therapy available for this condition—can reverse disease-associated changes, even when the underlying biology differs from that of the patients for whom the drug was originally developed.
HCM affects approximately one in 200 to 500 people and is the leading cause of sudden cardiac death in young adults and athletes. The disease is characterized by abnormal thickening of the heart muscle, impaired relaxation, and excessive contractility, which can ultimately lead to heart failure, arrhythmias, and sudden cardiac death.
Most inherited cases are caused by variants in either MYH7, which encodes the molecular motor myosin, or MYBPC3, which encodes cardiac myosin-binding protein C (cMyBP-C), an important regulator of cardiac muscle contraction.
While truncating mutations in MYBPC3 reduce levels of cMyBP-C and promote excessive myosin activity, much less has been known about how missense mutations—which preserve protein levels but alter protein function—drive disease.
To investigate this question, researchers generated a knock-in mouse model carrying the R502W missense mutation, one of the most common pathogenic MYBPC3 variants found in patients with HCM. Unlike mice lacking cMyBP-C, the R502W animals maintained normal amounts and localization of the protein yet still developed hallmark features of hypertrophic cardiomyopathy, including cardiac hypertrophy, fibrosis, impaired cardiac function, and hypercontractility.
“Our findings support that mutation-induced loss of interactions between the central domains of cMyBP-C and myosin is a molecular pathomechanism in HCM that can be targeted by myosin inhibitors,” the authors write.
Rather than reducing protein abundance, the mutation weakened the interaction between cMyBP-C and myosin, shifting more myosin molecules into an active structural state capable of generating contraction. The mutation also increased calcium sensitivity, together producing excessive contractile force.
Importantly, these abnormalities arose through a mechanism distinct from the loss-of-protein pathway associated with truncating MYBPC3 mutations.
Despite these divergent disease mechanisms, treatment with mavacamten significantly reduced pathological remodeling in both the R502W mice and animals lacking cMyBP-C. The drug also restored a more normal inactive structural state of myosin in mutant heart muscle and reduced excessive contraction in engineered human heart tissues carrying the same mutation.
“Hence, our data and evidence in the literature suggest that mavacamten is equally effective for carriers of any pathogenic variant in MYH7 or MYBPC3,” the authors conclude. The findings may help explain why genetic differences alone are unlikely to account for the variable clinical responses observed in patients receiving mavacamten.
The work also has implications beyond current therapies. Because some emerging gene therapies aim to replace cMyBP-C rather than correct mutant protein function, the authors suggest those approaches may be less effective for patients carrying missense mutations such as R502W. By contrast, gene-editing strategies capable of directly correcting single-base mutations may prove particularly promising.
The researchers also propose that the newly developed mouse model more closely resembles the relatively mild progression of human hypertrophic cardiomyopathy than previous models based on complete cMyBP-C deficiency, making it a valuable platform for testing future therapies and studying disease biology.
Looking ahead, the investigators suggest that most patients carrying pathogenic MYBPC3 variants could potentially benefit from myosin inhibition regardless of the mutation’s underlying molecular mechanism.
“Our preclinical data indicate that all carriers of pathogenic variants in MYBPC3, arguably the most common cause of HCM, may similarly benefit from myosin inhibition regardless of diverging specific pathomechanisms,” the authors conclude. They add that the limited effectiveness of mavacamten observed in some patients is “probably due to reasons other than the specific HCM variants they carry,” including disease stage, environmental influences, or other genetic factors.
The post New Clues to Inherited Heart Disease Point to Broader Role for Mavacamten appeared first on Inside Precision Medicine.
STAT+: FDA approves Vera Therapeutics kidney disease treatment
The Food and Drug Administration on Tuesday approved a new medicine from the biotech company Vera Therapeutics for patients with a type of chronic autoimmune kidney disease.
The drug, called Trutakna, was cleared to treat IgA nephropathy, or IgAN, a disease caused by the buildup of immune antibodies in the kidneys. The condition leads to progressive loss of kidney function and potentially organ failure requiring dialysis.
“We’re extremely excited to bring Trutakna to patients,” Vera CEO Marshall Fordyce told STAT, in an interview conducted ahead of the FDA approval.