The underlying mechanism of scorpion venom peptide BmK AS in reducing epilepsy seizures: mediated through dual modulation of Nav1.6 and the inflammasome pathway

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  The underlying mechanism of scorpion venom peptide BmK AS in reducing epilepsy seizures: mediated through dual modulation of Nav1.6 and the inflammasome pathway Abstract Introduction:  Voltage-gated sodium channel (VGSC) dysregulation, particularly of the Nav1.6 subtype, is a core mechanism underlying epileptogenesis and its associated neuropsychiatric comorbidities. The scorpion venom peptide BmK AS has demonstrated anticonvulsant potential, but its efficacy in chronic epilepsy and the precise mechanisms of action remain undefined. Methods:  Here, we show that BmK AS exerts robust anti-epileptic and neuroprotective effects through converging mechanisms. In a kainic acid-induced mouse model, BmK AS treatment reduced mortality and seizure parameters. Electrophysiological studies assessed BmK AS modulation of VGSC subtypes. The functional relevance of Nav1.6 targeting was confirmed by the loss of BmK AS’s anti-seizure efficacy upon its pharmacological blockade in a PTZ-in...

Scorpion sting envenomation: a neglected tropical disease in the shadow of global health priorities: an urgent call to action

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Scorpion sting envenomation: a neglected tropical disease in the shadow of global health priorities: an urgent call to action

‘Scorpion sting envenomation meets all the criteria to be recognised as a neglected tropical disease, yet it remains overlooked and excluded from the official WHO list of neglected tropical diseases. The lack of formal recognition is, in itself, a barrier to achieving global health equity and preventing avoidable deaths in vulnerable communities, particularly among children in tropical and subtropical regions across the globe’, argue Carlos Castillo-Salgado and colleagues.

Scorpion sting envenomation (SSE) is a life-threatening medical condition caused by the venom of certain scorpion species, posing a significant public health burden in tropical and subtropical regions. Each year, SSE leads to thousands of deaths and severe complications, disproportionately affecting vulnerable populations with limited access to timely treatment, especially children under 10 years of age.1 2 The WHO defines neglected tropical diseases (NTDs) as ‘a diverse group of conditions caused by a variety of pathogens (including viruses, bacteria, parasites, fungi and toxins) associated with devastating health, social and economic consequences’.3 NTDs primarily affect impoverished communities in tropical regions and impact more than one billion people worldwide. Their epidemiology is complex, often influenced by environmental, geographical and social conditions, making public health control efforts challenging.3 In 2018, Benin and Morocco proposed SSE for recognition as an NTD by WHO.4 The request was reviewed by a three-member subcommittee of the WHO Strategic and Technical Advisory Group (STAG) for NTDs and the WHO secretariat. Two members concluded that SSE did not meet the NTD criteria, citing ‘extremely rare mortality, lack of long-term disability and difficulties in defining a broad control strategy’. Consequently, STAG did not recommend its inclusion as an NTD.4 However, new evidence challenges these previous conclusions, allowing for a reassessment of SSE’s classification. Today, robust and compelling data demonstrate that SSE meets all WHO criteria for NTD recognition. This letter presents evidence-based arguments for the urgent reconsideration of SSE as an NTD, considering new data that addresses previous objections and underscores its significant and underestimated public health impact.

Scorpions are found on every continent except Antarctica, some islands and boreal regions. Their adaptability allows them to thrive in a wide range of environments (arid, tropical and temperate regions). Scorpions exhibit notable resilience to pesticide treatments, and certain species of sanitary significance (eg, Tityus serrulatus) can withstand extreme environmental conditions, including prolonged periods of starvation lasting over a year, which complicates efforts to control SSE.2 5 Additionally, some of these species reproduce through parthenogenesis, allowing them to rapidly establish and expand populations.5 This combination of widespread distribution and survival capabilities puts more than 30% of the global population at risk of SSE.2 6 Fourteen scorpion genera (figure 1) and >150 species (table 1) are considered medically relevant worldwide, with key taxa distributed in 44 countries, where severe/lethal SSE cases have been reported, spanning five of the six WHO Health Regions: the Americas (13 countries: genera Centruroides, Tityus, Jaguajir), Eastern Mediterranean (18 countries: Androctonus, Buthus, Mesobuthus, Parabuthus, Odontobuthus, Nebo, Hottentotta, Hemiscorpius, Leiurus, Olivierus), African (7 countries: Androctonus, Buthus, Hottentotta, Leiurus, Parabuthus), European (2 countries: Aegaeobuthus, Androctonus, Nebo, Hottentotta, Leiurus) and South-East Asian (3 countries: Hottentotta).2 5 7 The following are three key aspects used by WHO to classify NTDs, as applied to the context of SSE.3

Hernández Muñoz EA, Borges A, Zavala-Sánchez EV, Rojas de Arias A, Oukkache N, de Souza CMV, et al. Scorpion sting envenomation: a neglected tropical disease in the shadow of global health priorities: an urgent call to action. BMJ Global Health. 2025;10:e020682. https://doi.org/10.1136/bmjgh-2025-020682