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Recent study investigates the expression of mitofusin 2 (Mfn2) in placentas and peripheral blood from patients with early-onset preeclampsia (eoPE) and late-onset preeclampsia (loPE), exploring its potential as a diagnostic and therapeutic target for preeclampsia. Preeclampsia, a serious condition occurring after 20 weeks of gestation, presents significant morbidity and mortality risks, particularly differentiating between eoPE (before 34 weeks) and loPE (after 34 weeks) due to varying placental and maternal pathophysiologies.

Role of Mfn2 in Preeclampsia

Mfn2, a mitochondrial outer membrane protein critical for mitochondrial dynamics, was previously noted to be downregulated in preeclampsia, associated with increased apoptosis and mitochondrial dysfunction. The study emphasizes the differences in placental pathology between eoPE and loPE, highlighting impaired remodeling of uterine spiral arteries in eoPE, leading to ischemia and hypoxia. In contrast, loPE presents with maintained or higher placental perfusion levels.

Mfn2 Expression Analysis

Quantitative assessments revealed a significant decrease in Mfn2 mRNA levels in placentas from eoPE patients compared to both loPE and normal control groups, while loPE did not show significant downregulation compared to controls. Peripheral blood analyses indicated higher levels of Mfn2 protein in both preeclampsia groups compared to controls, with eoPE showing the highest levels. Notably, Mfn2 levels were positively correlated with the severity of preeclampsia, such as systolic and diastolic blood pressure and proteinuria, with stronger correlations in eoPE. The findings suggest a stratification in the role of Mfn2 between the two conditions, establishing that the reduction of Mfn2 in eoPE is indicative of significant mitochondrial dysfunction, while the elevated serum levels in both preeclampsia types may reflect a compensatory response to placental mitochondrial damage. Moreover, these elevated Mfn2 levels were negatively correlated with birth weight and Apgar scores, indicating poor pregnancy outcomes associated with elevated Mfn2 levels.

Conclusion and Future Directions

In summary, this investigation highlights Mfn2’s potential as a biomarker for preeclampsia severity and progression, distinguishing the distinct roles of mitochondrial dysfunction in eoPE and loPE. The findings support the hypothesis that early identification of impaired Mfn2 expression could facilitate enhanced diagnostic and therapeutic strategies for preeclampsia management, advocating for further research to validate these findings in larger cohorts and longitudinal studies.

Key Points

– -Expression Analysis of Mfn2-: Significant downregulation of Mfn2 mRNA levels was identified in placentas from patients with early-onset preeclampsia (eoPE) when compared to both late-onset preeclampsia (loPE) and normal control samples, while loPE did not exhibit significant differences in Mfn2 levels compared to controls.

– -Peripheral Blood Findings-: Elevated Mfn2 protein levels were observed in peripheral blood from both eoPE and loPE patients compared to controls, with eoPE showing the highest serum Mfn2 levels. This suggests a potential compensatory mechanism in response to placental mitochondrial damage.

– -Correlation with Disease Severity-: Mfn2 levels exhibited positive correlations with the severity of preeclampsia indicators such as systolic and diastolic blood pressure, as well as proteinuria. These correlations were found to be more robust in the eoPE cohort, indicating that altered Mfn2 expression may reflect the severity of the condition.

– -Implications for Pregnancy Outcomes-: Elevated Mfn2 levels in both types of preeclampsia were negatively correlated with birth weight and Apgar scores, suggesting that higher Mfn2 may be associated with adverse pregnancy outcomes and poorer fetal health.

– -Differentiation of Pathophysiology-: The study emphasizes the divergent mechanisms of placental pathology between eoPE and loPE, with eoPE characterized by impaired remodeling of uterine spiral arteries, leading to ischemic conditions, whereas loPE maintains or improves placental perfusion levels.

– -Future Research Directions-: The findings propose Mfn2 as a potential biomarker for assessing preeclampsia severity and progression, underscoring the need for further investigations in larger cohorts and longitudinal studies to validate Mfn2’s utility in diagnostic and therapeutic approaches for preeclampsia.

Reference –

Dandan Sun et al. (2025). A Mitochondrial Regulator Protein, Mitofusin 2, Is Elevated In The Maternal Blood Of Women With Preeclampsia. *BMC Pregnancy And Childbirth*, 25. https://doi.org/10.1186/s12884-025-07663-4.

Following the death of a 9-year-old girl from amoebic encephalitis— a rare and often fatal brain infection caused by free-living amoeba commonly found in contaminated water, health authorities in Kozhikode have issued a high alert.

The child was first admitted to a local hospital last week with a high fever. As her condition worsened rapidly, she was shifted to Kozhikode Medical College. Despite treatment, she succumbed on the same day.

According to health officials, this is the fourth case reported from Kozhikode
this year — raising concerns about possible contaminated water sources in the
district. Efforts are now underway to trace the exact pond or water body where
the infection may have been contracted. Doctors explain that the infection is
usually caused by Naegleria fowleri, often referred to as the “brain-eating
amoeba.”

It thrives in warm freshwater lakes, rivers, and ponds. Infection
occurs when contaminated water enters the nose, usually during swimming or
diving, before reaching the brain. What makes it dangerous?

Symptoms such as severe
headache, fever, vomiting, stiff neck, and confusion appear suddenly,
progressing rapidly to coma. The fatality rate stands at over 97%, even with
treatment. Is it treatable?

Doctors use antifungal drugs like amphotericin B,
often in combination with miltefosine and other medicines, but survival remains
rare. Early detection is critical. How can you stay safe?

Avoid swimming or
watersports in warm freshwater bodies. Never use tap water in nasal rinsing
devices (like neti pots) — only distilled or sterilized water. Ensure proper
chlorination of swimming pools. Health experts emphasize: If you develop sudden
fever or headache after swimming in freshwater, seek medical help immediately.

A new study published in the journal of Heart Rhythm showed that in individuals with atrial fibrillation, amiodarone therapy was independently linked to a higher incidence of thyrotoxicosis.

A common treatment for potentially fatal arrhythmias is amiodarone. Despite the fact that amiodarone has few adverse effects, 15-20% of patients may experience thyroid dysfunction. Amiodarone-induced thyrotoxicosis (AIT) is a serious side effect that can exacerbate heart failure and lead to arrhythmia recurrence.

While type II AIT is a destructive thyroiditis that reacts to glucocorticoids, type I AIT is often treated with thionamides and occurs in people who already have thyroid disease. There is a mixed kind that is linked to increased mortality, particularly in older persons with heart disease. For individuals who are intolerant or resistant to medical therapy, thyroidectomy is regarded as a last resort.

Research on the possibility of amiodarone-treated individuals developing thyrotoxicosis instead of hypothyroidism is yet lacking. Thus, this study evaluated the relationship between amiodarone and thyrotoxicosis in individuals who were diagnosed with hypothyroidism concurrently with atrial fibrillation (AF).

This research used the Clalit Health Services database to do a population-based retrospective cohort analysis. 2 distinct cohorts, 1 for hypothyroidism and the other for normal thyroid function, were identified from patients who received a new diagnosis of AF between 2010 and 2023. Amiodarone exposure was investigated as a time-dependent variable using Cox proportional hazard regression, which allowed participants to switch between exposure groups throughout follow-up.

The hypothyroidism cohort comprised 23,854 AF patients, of whom 107 (66 of 8,212 amiodarone users and 41 of 15,622 non-users) had thyrotoxicosis during follow-up.

This represents a crude incidence rate of 3.43 and 0.63 per 1000 person-years for amiodarone users and non-users, respectively. Amiodarone had an adjusted-HR of 5.18 (95% CI, 3.48-7.69) and was independently linked to an elevated incidence of thyrotoxicosis in this sample.

With an adjusted-HR of 15.02 (95% CI, 13.56-16.64) and an incidence rate of 19.78 and 1.14 per 1000 person-years for amiodarone users and non-users, respectively, the amiodarone impact was more pronounced in individuals with normal thyroid function. Overall, although amiodarone has a less impact on thyrotoxicosis risk in hypothyroidism patients, the risk is still high and should be used with caution.

Source:

Ryan, D., Gershinsky, R., Gronich, N., Yahav, A., Barnett-Griness, O., Schliamser, J. E., Saliba, W., & Danon, A. (2025). Association between amiodarone and thyrotoxicosis in patients with atrial fibrillation and hypothyroidism. Heart Rhythm: The Official Journal of the Heart Rhythm Society. https://doi.org/10.1016/j.hrthm.2025.08.003

The U.S. Food and Drug Administration has approved Tonmya (TNX-102 SL), a sublingual formulation of cyclobenzaprine HCl for the treatment of adults with fibromyalgia. This marks the first new drug approval for fibromyalgia in over 15 years, offering a much-needed option for patients. Tonmya is designed to target two core aspects of the condition-nonrestorative sleep and chronic pain-making it a significant advancement in the management of fibromyalgia.

The FDA is expected to assign the NDA a Prescription Drug User Fee Act (PDUFA) target action date in a Day 74 Letter. At that time, the FDA will also communicate to Tonix whether Priority Review has been granted. TNX-102 SL was granted Fast Track designation for fibromyalgia by the FDA in July of 2024. Fast Track is designed to expedite FDA review of important new drugs to treat serious conditions and fill an unmet medical need.

“The FDA’s acceptance of our NDA represents another step forward as we pursue our goal of delivering the first member of a new class of medicines for the management of fibromyalgia, a condition affecting over 10 million adults in the U.S.,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “The fibromyalgia community, comprised of patients and their families and support groups, has been waiting for a new drug for over 15 years. Analysis of insurance claims in the U.S., commissioned by Tonix, have shown that 18 months after diagnosis, fibromyalgia patients were more likely to be prescribed addictive opioids than all three of the FDA-approved drugs combined.”

Dr. Lederman continued, “We look forward to working closely with the FDA throughout the NDA review period with the goal of bringing TNX-102 SL to the market to address the significant unmet needs of the fibromyalgia community as quickly as possible. Furthermore, this is an important milestone as we advance our commercial preparations in anticipation of a potential approval in 2025 with an accomplished commercial leadership team already in place, supporting our marketed products Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg for the treatment of acute migraine with or without aura in adults.”

The NDA is supported by data from two 14-week double-blind, randomized, placebo-controlled Phase 3 clinical trials evaluating the safety and efficacy of TNX-102 SL as a bedtime treatment for fibromyalgia. The first Phase 3 trial, RELIEF, of TNX-102 SL 5.6 mg in fibromyalgia, completed in December 2020, met its pre-specified primary endpoint of significantly reducing daily pain compared to placebo (p=0.010). In the confirmatory Phase 3 RESILIENT study in fibromyalgia, completed in December 2023, TNX-102 SL again met the pre-specified primary endpoint of significantly reducing daily pain compared to placebo (p =0.00005). In both trials, TNX-102 SL was generally well tolerated with an adverse event profile comparable to prior studies and with no new safety signals observed. In both pivotal studies, the most common treatment-emergent adverse event was tongue or mouth numbness at the administration site, which was temporally related to dosing, self-limited, never rated as severe, and rarely led to study discontinuation (one participant in each study). Excluding COVID-19, systemic adverse events in each of the two studies was lower than 4.0%. Tonix believes the submitted dossier contains the requisite safety and efficacy data from two adequate and well-controlled studies to support NDA approval.

About Fibromyalgia

Fibromyalgia is a common chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system, called central sensitization. Brain imaging studies have localized the functional disorder to the brain’s insula and anterior cingulate cortex. Fibromyalgia afflicts more than 10 million adults in the U.S., the majority of whom are women. Symptoms of fibromyalgia include chronic widespread pain, non-restorative sleep, fatigue, and brain fog (or cognitive dysfunction). Other associated symptoms include mood disturbances, including depression, anxiety, headaches and abdominal pain or cramps. Individuals suffering from fibromyalgia often struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products. Fibromyalgia is now recognized as the prototypic nociplastic syndrome. Nociplastic pain is the third primary type of pain in addition to nociceptive pain and neuropathic pain.

Many patients present with pain syndromes that are a spectrum of mixtures of the three primary types of pain. Nociplastic syndromes are associated with central and peripheral sensitization. Fibromyalgia can occur without any identifiable precipitating event. However, many fibromyalgia cases follow one or more precipitating event(s) including: post-operative pain, acute or chronic nociceptive or neuropathic pain states; recovery from an infectious illness; a cancer diagnosis or cancer treatment; a metabolic or endocrine stress; or a traumatic event. In the cases of recovery from an infectious illness, fibromyalgia is considered an Infection-Associated Chronic Condition. In addition to fibromyalgia cases associated with other conditions or stressors, the U.S. National Academies of Sciences, Engineering, and Medicine, has concluded that fibromyalgia is a diagnosable condition that can occur after recovery from COVID-19 in the context of Long COVID. Fibromyalgia is also recognized as a Chronic Overlapping Pain Condition, which is a group of related conditions including, chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), irritable bowel syndrome, endometriosis, low back pain, post-concussive syndrome (also known as mild traumatic brain injury), chronic Lyme Disease, chronic diabetic neuropathy and chronic post-herpetic neuralgia.

About TNX-102 SL

TNX-102 SL is a centrally acting, non-opioid investigational drug, designed for chronic use. The tablet is a patented sublingual formulation of cyclobenzaprine hydrochloride developed for bedtime dosing for the management of fibromyalgia. Cyclobenzaprine potently binds and acts as an antagonist at four different post-synaptic neuroreceptor subtypes: serotonergic-5-HT2A, adrenergic-α1, histaminergic-H1, and muscarinic-M1-cholinergic receptors. Together, these interactions are believed to target the non-restorative sleep characteristic of fibromyalgia that was identified by Professor Harvey Moldofsky in 1975. Cyclobenzaprine is not associated with risk of addiction or dependence.

The TNX-102 SL tablet is based on a eutectic formulation of cyclobenzaprine HCl and mannitol that provides a stable product which dissolves rapidly and delivers cyclobenzaprine by the transmucosal route efficiently into the bloodstream. The eutectic protects cyclobenzaprine HCl from interacting with the basifying agent that is also part of the formulation and required for efficient transmucosal absorption. Patents based on TNX-102 SL’s eutectic composition and its properties have issued in the U.S., E.U., Japan, China and many other jurisdictions around the world and provide market protection into 2034. The European Patent Office’s Opposition Division maintained Tonix’s European Patent EP 2 968 992 in unamended form after an Opposition was filed against it by a Sandoz subsidiary, Hexal AG. Hexal AG did not appeal that decision.

The formulation of TNX-102 SL was designed specifically for sublingual administration and transmucosal absorption for bedtime dosing to target disturbed sleep, while reducing the risk of daytime somnolence. Clinical pharmacokinetic studies indicated that relative to oral cyclobenzaprine, TNX-102 SL results in higher levels of exposure during the first 2 hours after dosing and in deceased levels of the long-lived active metabolite, norcyclobenzaprine in both single dose and multiple dose studies, consistent with bypassing first pass hepatic metabolism. At steady state after 20 days of dosing TNX-102 SL, the dynamic peak level of cyclobenzaprine is higher than the background level of norcyclobenzaprine. In contrast, after 20 days of dosing oral cyclobenzaprine, the simulated peak level of cyclobenzaprine is lower than the simulated background level of norcyclobenzaprine.