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. 2025 Jul:57:72-81.
doi: 10.1016/j.ejpn.2025.05.012. Epub 2025 May 29.

Key lessons from the first international treatment eligibility committee: the case of metachromatic leukodystrophy

Daphne H Schoenmakers  1 , Marije A B C Asbreuk  1 , Tamara Martin  2 , Mareen Datema  3 , Shanice Beerepoot  4 , Michal Inbar-Feigenberg  5 , Samuel Groeschel  6 , Christiane Kehrer  6 , Andreas Øberg  7 , Caroline Sevin  8 , Francesca Fumagalli  9 , Caroline G Bergner  10 , Päivi Vieira  11 , Annette Bley  12 , Johanna Uusimaa  11 , Morten Andreas Horn  13 , Klára Brožová  14 , Eva Stögmann  15 , Herbert Pichler  16 , Roswitha Lüftinger  16 , Erik A Eklund  17 , Fanny Mochel  18 , Laura A Adang  19 , Lucia Laugwitz  20 , Jaap Jan Boelens  21 , Valeria Calbi  22 , Alejandra Darling  23 , Ángeles García-Cazorla  23 , Sabine W Grønborg  24 , Caroline A Lindemans  25 , Peter M van Hasselt  26 , Carla E M Hollak  27 , Tom J de Koning  28 , Dipak Ram  29 , Hanka Dekker  30 , Ludger Schöls  31 , Ayelet Zerem  32 , Holm Graessner  2 , Nicole I Wolf  33
Affiliations
Free article

Key lessons from the first international treatment eligibility committee: the case of metachromatic leukodystrophy

Daphne H Schoenmakers et al. Eur J Paediatr Neurol. 2025 Jul.
Free article

Abstract

Background: Treatment decisions in metachromatic leukodystrophy (MLD), a rare life-threatening neurological disease, are challenging. Hematopoietic stem cell transplantation or autologous stem-cell-based gene therapy can be life-changing but come with uncertainties, risks, and high costs. To address this, the international MLD treatment eligibility panel was established in collaboration with the European Reference Network on Rare Neurological Diseases. The panel reviews and discusses individual MLD cases and provides consensus-based recommendations on whether to treat and which treatment modality. The goal is to streamline international care and treatment counseling by providing uncomplicated access to expert opinion.

Methods: The panel operates according to a published standard operating procedure and was evaluated between September 2021-2024. Case data were recorded in a Castor EDC-based system and, with consent, included in the MLD Initiative (MLDi) patient registry. Physicians' experiences were assessed via EUsurvey, and patients' feedback was collected through an MLDi registry survey.

Findings: The panel discussed 43 cases, recommending treatment in 20, abstaining in 19, and reaching no consensus in 4. Open questions regarding cognitive function and lack of outcome data caused challenges in treatment recommendations in late-onset MLD patients. All treatment recommendations were followed. Physicians reported positive experiences with the panel.

Interpretation: The MLD treatment eligibility panel demonstrates how international expert advice can be streamlined across Europe for a rare disease like MLD, where disease-specific guidelines are still in development. By balancing complex clinical, social, and ethical parameters, the panel aids in encouraging appropriate use of innovative and costly therapies and guarantees accessibility to expert advice irrespective of country of origin.

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Conflict of interest statement

Declaration of competing interest The following declarations of interest were reported with regard to the current manuscript in the past 36 months. LAA has a non-paid role as scientific advisor for CureMLD, the MLD foundation, and Don't forget Morgan. SB and DHS received an ERN-RND travel grant to present ERN-RND related results at the European Paediatric Neurology Society Congress in 2022. MI-F participated in the Takeda enzyme replacement study for MLD. AB received a travel grant from Orchard Therapeutics. VC and FF received occasional consulting fees, support for attending meetings or payment for lectures from Orchard Therapeutics. HG and TM is affiliated to ERN-RND and received a Grant from the European Commission to support the European Reference Network for Rare Neurological Diseases, and received a consulting fee from UCB for the Aspire4Rare project. JJB received grants or consulting fees from Sanofi, Sobi, and Merck. SG received (institutional) research grants from DFG, Takeda and Orchard and received institutional consulting fees from Takeda, Sanofi, and Orchard. SWG received travel or consulting fees from Orchard Therapeutics and Sanofi. CL received a travel grant from Orchard Therapeutics. AØ participated in the advisory board of Orchard Therapeutics without payments. HP received travel grants from Neovii AND Jazz Pharma and participated in an advisory board from Vertex. LS received a grant ZMVI1-2520DAT94E from the Ministry of Health (BMG) for LeukoExpert and is the (unpaid) corresponding author of guidelines on leukodystrophies in adulthoord by the German Society of Neurology (DGN). NIW received institutional grant from ZonMw, is local PI for a studies from Ionis and Vigilneuro, is consultant for Sana Biotech, Ionis, VigilNeuro and Lilly (with payment to the institution) and participates in scientific advisory boards of the patient organizations ULF, ELA, and Yaya foundation without payment, and is unpaid member of the editorial boards of Neurology and EJPN. The other authors have nothing to declare: DR, MABCA, CB, KB, AD, HD, EE, AG-C, CEMH, MAH, CK, TJK, LL, CS, JU, PV, AZ, ES.

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