The seventh edition of the international TALENT Meeting took place in recent days, organized together with the European Endo-ERN network and the Precision Medicine partnership HEAL Italia
One of the most problematic issues in the rare disease sector concerns the transition from pediatric to adulthood, a process that can be defined as the “targeted and well-planned movement of the adolescent affected by a chronic disease from child-centered to adult-oriented health care systems”. It is therefore not a mere “transfer”, but rather an organized transition that includes the adaptation of treatment plans and the activation of a network of specialists dedicated to the needs of the individual who becomes an adult. A path that continually evolves thanks to new diagnostic and therapeutic discoveries and the personalization of medicine. Unfortunately, in some circumstances the bridge that allows patients to continue the treatment process without interruptions is not created, and this is even more true for rare diseases of the endocrine system.
For this reason, a team of experts is needed to collaborate to generate efficient pathways in particularly difficult rare diseases such as, for example, adrenoleukodystrophy, hypophosphatemic rickets and some rare forms of obesity and diabetes. With these premises, the “think-tank” TALENT was born in 2018, which meets periodically in Rome: this year the official meeting took place between 12 and 13 February.
TALENT: AT THE SERVICE OF THE TRANSITION FROM PEDIATRIC TO ADULT AGE
“Now in its seventh edition, the international meeting TALENT – Transition of care Working Group – aims to respond to a cultural and care gap surrounding the transition from pediatric to adulthood in endocrine diseases and, in particular, rare diseases”, says Prof. Andrea M. Isidori, Full Professor of Endocrinology at Sapienza University of Rome and head of the Advanced Diagnostics Unit in Endocrinology at Umberto I. “Since the first edition, we have brought together expert pediatric clinicians and adult endocrinologists, both in training and active in scientific research, selecting ever-changing topics that presented management problems and cultural gaps that made patient care difficult. After the conclusion of each event, we tried to make the participants, young and experienced, work in synergy, in order to share data and develop together new diagnostic therapeutic care pathways (PDTA), observational studies, guidelines and consensus, to make practice and clinical research increasingly focused on the needs of patients. The ambition of TALENT is a precision medicine that becomes personalized medicine”.
The difficulty of carrying out clinical trials for diseases that have only a few hundred cases throughout the country (if not in the world) is an obstacle to overcome; even more so is the transition from pediatric to adulthood, where data is scarce and it is necessary to rely on Real Life experiences, to obtain useful information to promote the construction of valid models. The transition, in fact, requires the continuous provision of primary care, without neglecting the psychological and social support that the families of young patients need most: for this reason it requires specific and applicable models.
Over the years, the progress made by the meeting of experts at the TALENT meetings has led to the publication of numerous scientific articles, attracting the attention of the experts of the Endo-ERN network – the most important European reality dedicated to endocrine disorders, which brings together the main reference centers across Europe for a wide range of diseases. “Due to the commitment and credibility achieved, in 2024 the Endo-ERN entrusted us with the task of leading the working group on the transition, which has a transversal nature on all rare diseases, involving several other ERN networks”, Isidori specifies. “Since last year we had already started to bring Europe into our model, integrating it with that of other European realities, but with the latest edition of TALENT we managed to bring the entire Endo-ERN working group to Rome – around 22 experts from across Europe – with the aim of drawing up an international consensus on the paths of the transition. This document will represent an easy-to-use vademecum, containing the minimum but essential criteria to follow to ensure an effective and smooth transition that does not discriminate against any patient who is in less prepared areas or countries, providing healthcare professionals with a lever to overcome those barriers caused by lack of equity”.
MANY DISEASES, ONE SINGLE DENOMINATOR
One of the examples discussed at TALENT was adrenoleukodystrophy, a rare metabolic disease linked to the X chromosome, for which a transition pathway is already active that connects the IRCCS Ospedale Pediatrico Bambino Gesù and the Policlinico Umberto I in Rome. Prof. Marco Cappa, Head of the Research and Innovative Therapies Unit in Endocrinopathies at Bambino Gesù, spoke about it during the conference. “A multidisciplinary approach is needed,” he said. “Together with Prof. Isidori, I am working to ensure that it is possible to have a shared and reliable model, so that patients flow from one clinic to another and effectively continue their follow-up path.” In adrenoleukodystrophy, the membranes of peroxisomes [cellular organelles involved in the catabolism of various substances, Editor’s note] are unable to absorb very long-chain fatty acids (VLFCAs), which consequently accumulate in various areas of the body, including the central nervous system, the adrenal glands and the testes. “Adrenoleukodystrophy is a very complex metabolic disease,” Cappa specifies. “Patient care requires precise organization that guarantees continuation of pharmacological and nutritional therapy to reduce VLFCA levels.” In Italy, gene therapy for patients affected by this condition is no longer available, so neonatal screening to identify the disease remains a priority. “We are working to develop methods to identify early those who will develop the severe form (X-CALD), studying them with lipidomics and oxidation-reduction methods in the blood and fibroblasts,” adds Cappa. “Follow-up at the pediatric center is constant, and the subsequent transfer is carried out to an adult center with robust endocrinological, nutritional and neurological experience, without ever interrupting the evaluations.”
The centrality of the multidisciplinary approach was also reiterated by Prof. Francesco Emma (Bambino Gesù Children’s Hospital) in a report dedicated to the advantages of targeted therapy with burosumab for young patients affected by X-linked hypophosphatemia. Over time, these children experience defects in bone mineralization, with growth delays and an increase in, among other things, the risk of fractures and dental problems, which have a profound impact on their quality of life.
At the end of the first day, ample space was dedicated to new technologies for diabetes management. Felix Reschke (Diabetes Center for Children and Young People in Hannover) illustrated the most recent developments in this field, focusing on both new sensors for monitoring blood glucose levels and advanced technological devices, such as the artificial pancreas, which are essential in preventing glycemic peaks, especially in the transitional age, when the greatest increases in glycated hemoglobin levels are observed (a sign of the difficulty in adequately controlling the pathology in this age group).
THE PROBLEMS OF THE TRANSITION
According to the current guidelines dedicated to transition, the key points to focus on to fill the gaps in this process are educational support and the creation of connections with adult experts. “We need to make sure that we design pathways tailored to the needs of the disease,” stressed Laura De Graaf, of the University Medical Center in Rotterdam, during a presentation dedicated to hypothalamic obesity at the beginning of the second day of the conference. Setting up a shared clinic between the child specialist and the adult specialist or establishing direct communication between the two, involving the patient and caregivers from the start, is essential for the success of the delicate transition phase.
The experience on multiple endocrine neoplasia – reported by Annemarie Verrijin-Stuart (Wilhelmina Kinderziekenhuis in Utrecht) – calls for the urgency of adopting shared pathways, channeling patients correctly, also through qualified and well-trained figures: many consider the presence of a dedicated figure, such as the transition coordinator, to be desirable. “This person cannot be a single doctor or nurse who occasionally deals with patients in transition”, specifies Isidori. “Anyone involved in the management of a rare disease is called to become a transition coordinator, aligning themselves with the realities in the territory and without ever neglecting some elements specific to the patient themselves”.
Some endocrine diseases are monitored for specific aspects that are relevant in pediatric age, while others, which become significant in adulthood, tend to be overlooked. “This is the case with pubertal development and the acquisition of sexual maturity,” Isidori said during his presentation on congenital hypogonadotropic hypogonadism, as part of a specific educational course promoted by the European Academy of Endocrinology (EAA). “In a pediatric context, these are more remote and less frequently discussed issues, but they are not of secondary importance. The alignment between pediatric and adult experts must be bidirectional, both in terms of efficiency of the response and respect for transition times.” A broad and detailed assessment of the patient necessarily changes the transition path, and efforts are being concentrated on this point, to promote education and develop new synergies between adult and pediatric experts. “The logic to adopt is that of the Hub and Spoke system, which guarantees the efficiency of the process,” concludes Isidori. “And this applies both to the acquisition of sexual maturity or reproductive potential, and to other issues, such as nutrition, which concerns individuals affected by hypophosphatemic rickets with skeletal disorders or those affected by genetic obesity.”
PRECISION MEDICINE IN TRANSITION
As European experts took turns on the TALENT stage, the need to promote shared knowledge to address the issues related to complex endocrine diseases in a prospective and far-sighted manner clearly emerged. To reduce disparities across the country and create multidisciplinary infrastructures and networks of experts, the “HEAL Italia” project was developed, supported by the Ministry of University and Research and financed with European funds from the PNRR. In a partnership logic, HEAL Italia brings together more than 70 scientific institutes and treatment centers in Italy, united by research in precision medicine. Now at the beginning of its third year of activity, HEAL Italia’s Spoke 4 – coordinated by Prof. Isidori himself – has proven to be a multiplier of skills in various sectors, and has also seen the involvement of numerous industrial partners, to develop innovative devices for the diagnosis of oncological, cardiovascular, metabolic and, of course, rare diseases. In particular, HEAL is developing new non-invasive diagnostic methods, such as the use of alternative biological samples, such as saliva or breath, or remote monitoring through wearable sensors, to reduce patient travel to diagnostic centers (particularly important for rare diseases that are managed in few centers) or, again, the use of artificial intelligence to extract more value from radiological images.
HEAL and TALENT represent a synergy of Italian excellence capable of uniting three souls: training, research and involvement of the territory. In this perspective of mutual collaboration, HEAL Italia and the Provincial Order of Physicians-Surgeons and Dentists (OMCeO) of Rome have released a survey in order to standardize the management of rare diseases and align the approaches offered by precision medicine among all healthcare professionals, from hospital centers to those on the front line in the territory. A significant effort to widen the network and operate in an increasingly multidisciplinary context.