The Treatabolome, an emerging concept

Abstract

It is with a great pleasure that we introduce the first special issue of the Journal of Neuromuscular Diseases dedicated to the “Treatabolome”, a new concept emerging from a European Project addressing unsolved rare diseases (Solve-RD, www.solverd.eu). Thus, this special issue covers gene and variantspecific treatments for rare diseases, particularly rare neurological and neuromuscular disorders, thereby highlighting the important premise that a precise genetic diagnosis may result in equally precise therapeutic approaches. Although such targeted treatments are currently only available to a minority of RD patients, recent developments point towards a steep increase in the coming years, as suggested by the development of multiple gene therapies and the steady increase in the number of orphan drug applications. One of the initial aims of the International Rare Diseases Research Consortium (IRDiRC), founded in 2011, was to contribute to the development of 200 new therapies for rare diseases by the year 2020, an objective reached ahead of schedule in 2016 [1]. They now propose 1000 new treatments by 2027 [2]. The need to increase the visibility of these treatments is the objective of the Treatabolome project within Solve-RD. This EU project aims at diagnosing unsolved rare disease cases and involves four European Reference Networks or ERNs (ERN-RND for Rare Neurological Diseases, ERN Euro-NMD for Rare Neuromuscular Diseases, ERN-ITHACA for rare congenital malformation and syndromes with intellectual and other neurodevelopmental disorders and ERN-GENTURIS for patients with one of the rare genetic tumour risk syndromes). Furthermore, it reaches out to the entire 24 ERNs networks and the undiagnosed disease programmes from Spain and Italy, following the ambitious goals set out by the IRDiRC to diagnose and subsequently treat a representative number of rare diseases. The growing availability of next generation genetic diagnostic tools is expanding the access to diagnosis even for patients that do not have access to primary expert evaluation. With this there is an evergrowing number of rare diseases’ therapies are not necessarily “on the radar” of non-expert clinicians, who however increasingly take care and/or diagnose these patients. The constitution of a database of rare disease-specific treatments directly linked to the gene and variant level will allow flagging already available therapies at the time of diagnosis. For that purpose, the treatabolome database will be interoperable with different diagnosis-support tools and will complement their existing datasets with specific treatment information. The treatabolome data will be findable, available, interoperable and reusable (i.e., the FAIR principles of data management, [3]) to benefit rare disease patients and their clinicians and shorten the interval from diagnosis to treatment. The Solve-RD project has invited expert teams to produce systematic literature reviews for rare diseases of their expertise and extract datasets of treatments for incorporation into the Treatabolome database. These systematic reviews shared a common structure, as detailed in a published methodology paper [4] and follow a pilot treatabolome publication on congenital myasthenic syndromes [5]. The treatabolome database incorporates these datasets, and an interoperable platform is under development to make available for users the data with existing clinical support, diagnostic tools and research systems, such as the RD-Connect’s Genome Phenome Analysis Platform (https://rd-connect.eu). The present ‘Treatabolome’ special issue of JND assembles five systematic reviews from prestigious reference centres representing a valuable