# ANEmone: The 1st Acute Necrotizing Encephalopathy
## Science & Family conference raises hope for an
### ultra-rare disease

Maëva Leplat, Sophie Desgraupes, Guillaume Beucher, Adrien Decorsière, Anouk Perrin, Suzon Perrin, Nathalie J Arhel

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Maëva Leplat, Sophie Desgraupes, Guillaume Beucher, Adrien Decorsière, Anouk Perrin, et al. ANEmone: The 1st Acute Necrotizing Encephalopathy Science & Family conference raises hope for an ultra-rare disease. Virologie, 2025. hal-05517879

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**ANEmone: The 1st Acute Necrotizing Encephalopathy Science & Family conference raises hope for an ultra-rare disease**

Maëva Leplat, Sophie Desgraupes, Guillaume Beucher, Adrien Decorsière, Anouk Perrin, Suzon Perrin, Nathalie J. Arhel*

Affiliation: Institut de Recherche en Infectiologie de Montpellier, Université de Montpellier, CNRS UMR9004, 1919 route de Mende, 34090 Montpellier, France

Correspondance: nathalie.arhel@cnrs.fr

In April 2025, the first-ever science-family symposium on Familial Acute Necrotizing Encephalopathy (ANE1) was hosted in Montpellier with funding from the ANRS-MIE (Emerging Infectious Diseases), the Institut de Recherche en Infectiologie (IRIM), the Université de Montpellier, and the Société française de virologie. The aim of the two-day meeting, co-organised by Nathalie Arhel (IRIM, Université de Montpellier, CNRS) and Kim Smith (ANE-International), was to connect families, doctors and scientists, to raise awareness and accelerate research (Figure 1).

ANE1 is a rare autosomal dominant disease linked to a point mutation in the gene *RANBP2* (RAN binding protein 2) and triggered by a febrile infection [1,2]. The causative mutation is extremely rare – affecting an estimated one in 1,000,000 individuals – its penetrance is low, and symptoms typically only emerge following viral infection. When disease does occur, however, it generally affects young and otherwise healthy children, has a dramatically rapid progression, can cause severe neurological damage and be fatal. Additionally, episodes can recur, frequently with increasing severity [6–9]. These elements make ANE1 both difficult to recognize and profoundly traumatic for affected families, who are often blindsided by the suddenness and severity of disease, and for whom the struggle following an episode can be unrelenting.

RANBP2 is a component of the nuclear pore complex, whose many functions include the regulation of RNA export to the cytoplasm, bidirectional transport of macromolecules, as well as the post-translational modification of certain proteins [3]. Although the mechanistic role of RANBP2 in ANE1 remains undetermined, several studies suggest that its inactivation compromises the quality control normally exerted on the export of cytokine mRNAs and viral RNAs, leading to an exacerbation of the inflammatory response during viral infection [4,5].

**Planning ahead**

Sixteen ANE1 families from twelve different countries (Australia, Austria, Belarus, Canada, Finland, France, Germany, Italy, Netherlands, New Zealand, UK, USA) were contacted and invited to attend the patient event. Many ANE1 children live with neurological or motor disabilities requiring special arrangements, and some families practice social distancing or home schooling to protect their children from circulating pathogens. Therefore, for most families, the trip to Montpellier marked an unprecedented journey, often their first visit to France or Europe.

Additionally, 18 scientists and clinicians from across the world (Canada, Denmark, Finland, France, Italy, Netherlands, Singapore, Tunisia, UK) were invited to participate. This group included, in particular, the neuropaediatricians who had directly cared for the invited families, as well as leading experts in clinical immunology, genetics, and virology.

In total, over 80 participants registered for the gathering, which we named ANEmone (Acute Necrotizing Encephalopathy Multidisciplinary Outreach Network) to reflect our ambition to connect families with the clinical and research communities (Figure 2). The event took place at a centrally located hotel in Montpellier offering high-quality facilities. Thanks to the generous support of official sponsors, registration, accommodation, and catering were provided free of charge to all participants. Additionally, a solidarity fund established in advance allowed to cover all local travel expenses for families.
## Practical considerations

Organizing the event required careful planning to ensure accessibility, safety, and smooth logistics. Since English was the official language of the meeting, simultaneous translation apps were used by many participants during the meeting. Additionally, a team made up of seven volunteers, and wearing colour-coordinated t-shirts, was available to answer any questions in the different languages we collectively spoke (English, French, German, Russian, Italian, Spanish). Masks were mandatory for all participants and hotel staff throughout the event to protect vulnerable attendees. The entire event was broadcast via Zoom, with a replay available online, making it widely accessible for those unable to attend.

Transportation was carefully coordinated in advance with local taxi drivers in Montpellier, to transport families to and from the train station, airport, hotel, and the Gui de Chauliac Hospital—where a monocentric clinical investigation on ANE1 was conducted in parallel to the meeting.

Finally, special attention was given to creating space for participants to connect or take time away from the conference. A dedicated side room was prepared for the 15 children attending ANEmone, which we equipped with a selection of games, books, soft toys, cushions and sofas, and films for the older children.

## An unprecedented opportunity for discussions

The ANEmone symposium featured presentations from researchers, clinicians and families (Figure 3), covering a broad spectrum of topics, ranging from the molecular mechanisms of RANBP2 and potential therapeutic approaches, to the emotional impact of the disease on families.

Additionally, round-table discussions provided a rare opportunity for families to address their questions directly to medical experts, on issues such as clinical course, viral triggers, research innovation, and guidance for their teenagers and young adult children living with ANE1. Clinicians, in turn, engaged families with questions about treatments, preventive strategies for recurrence, their view on vaccination, and mental health concerns.

The event also facilitated valuable discussions among clinicians, who spontaneously met up at the end of each day in Montpellier's historic center to discuss insights from their respective countries and debate on questions that had been raised during the day.

## Impact and future directions

The ANEmone event marked a turning point for both ANE1 families and the scientific community. For families, it represented a break from isolation with the opportunity to meet other affected families, a validation of their experiences, and the unexpected reassurance that ANE1 is not only recognised but actively being researched. Despite initial hesitations around travel, language, or emotional overload, families expressed a profound sense of connection and hope. This collective energy led to the formation of a new board committee for ANE-International (www.aneinternational.org).

Clinicians left with a strong commitment to draft an emergency protocol for patients with ANE, along with recommendations to prevent recurrence. For researchers, hearing first-hand accounts from families and clinicians, particularly about the critical moments in ICU (intensive care unit), brought a broader perspective on their work. Although the pathogenesis of ANE1 remains poorly understood, and questions persist about the genetic mechanisms, the symposium helped define the priorities for future research and laid the foundation for lasting international collaboration.

Thanks to ANEmone, there is now hope that such collaborative efforts might lead to the identification of new biomarkers for ANE1, to allow for accelerated diagnosis and improved patient care around the world, and to a better understanding of the molecular mechanisms triggering the episodes so we can prevent onset.

## Acknowledgements
We wish to extend our sincere thanks to all ANE1 families who took part in ANEmone, to the Société Française de Virologie for supporting this event, and to all our sponsors. We also thank the anonymous donors who donated via our crowdfunding page and the Grayson Legacy Support Fund who will cover part of the travel costs.

Maëva Leplat is a BIOTIN Master student (Université de Montpellier). The salaries of Sophie Desgraupes and Guillaume Beucher are supported by a grant from the Agence Nationale de la Recherche (ANR-23-CE15-0005-02). Adrien Decorsière and Nathalie Arhel are employed by the CNRS.

## Figure legends

**Figure 1:** Flyer of the ANEmone science and family event held in Montpellier end of April 2025, designed by Sarah Chisnall, an ANE family member.

<figure><img src="image_2.png" /><figcaption>**Figure 2:** ANEmone participants gathered outside the venue.</figcaption></figure>

<figure><img src="image_3.png" /><figcaption>**Figure 3:** Presentation of the clinical study InflammaNUP to ANE families.</figcaption></figure>
<figure><img src="image_4.png" /></figure>

References

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