Gene therapy for SPG52

The SPG52 program at UAB

The only SPG52 gene therapy program is at the Universitat Autònoma de Barcelona (UAB), in the Central Nervous System Gene Therapy Group led by Miguel Chillón (ICREA, Institut de Neurociències UAB and Vall d'Hebron Research Institute) and Assumpció Bosch (UAB), with collaborators at IDIBELL and Hospital Germans Trias i Pujol and an international network that includes the SPG50 team at UT Southwestern and the Boston registry team [25,50]. The therapy is an AAV vector carrying a working copy of AP4S1 [25].

What UAB has announced. In December 2024 the university reported first positive preclinical results: in neurons grown from the stem cells of a child with SPG52, the treatment restored ATG9A function; in a mouse model it normalised the muscle response to nerve impulses, the effect lasted at least one year, and motor coordination and learning improved significantly [25]. The stated next steps were to finish the animal analyses, run the efficacy, biosafety and toxicity studies (the "third phase"), publish the results, and then apply to the Spanish Agency of Medicines (AEMPS) for a clinical trial [25,26]. In May 2025 UAB reported that the third phase was in its initial stages [26].

What has not happened yet. No peer-reviewed paper or preprint of the preclinical data has been published. No clinical trial application has been filed in Spain, the EU or the US. No SPG52 trial is registered anywhere. No timeline has been given, and no one can honestly give a date.

Who funds it. The program has been funded since 2019 by family associations, above all a Spanish family association, and by public crowdfunding through UAB's own page, with a further Romanian family association joining in 2025 [26,50,51]. Families in other countries, including the United States, give through the paths on the donate page.

Why funding is still needed

Funding is still needed.

The third phase of the preclinical program, the safety and toxicology studies, is fully funded and the team is already working on it. But time moves on and resources run out. If funds are not raised now and later stages cannot be paid for, the work must stop, wait, and restart, which means losing time.

Concrete figures per item cannot be given, because they depend on experimental results, regulatory requirements and timelines.

That is why families in every country are raising money now, for the stages after this one, so that the program never has to pause. Every path on the donate page funds the same work.

The other AP-4 programs, and why they matter for SPG52

SPG50 (AP4M1) is the furthest along and the template. The vector was built at UT Southwestern with Boston Children's and the NIH; in mice, earlier treatment at higher dose worked best and the benefit was partial [40]. The first child was treated in Toronto in March 2022; at 12 months there were no serious adverse events and the authors described preliminary stabilisation [29]. A Phase 1/2 trial in Dallas has treated four children, about ten children worldwide had received the therapy by October 2025 including under expanded access in Spain [44], and a Phase 3 trial started in April 2026 in Dallas and Barcelona [31]. The sponsor's stated aim is FDA approval by early 2028; that is an aim, not a regulatory commitment [45,46]. The Phase 3 enrols SPG52 children aged 4 to 72 months as untreated controls: see the first 90 days.

SPG47 (AP4B1): a therapy developed in Sheffield, with preclinical results published in 2024 [57], received FDA clearance for a trial in May 2025 [58]. The trial is registered at Boston Children's for five children aged 12 to 60 months and is "not yet recruiting"; recruitment may begin once funding is secured [32,37,56].

Because the four AP-4 conditions are one disease [2], each program clears a path for the next: the same virus shell, similar routes of administration, similar safety questions, and the same regulators. A working SPG50 therapy is the strongest argument that an SPG52 therapy can follow.

What gene therapy can and cannot do

In the mouse studies, earlier treatment at higher dose worked best and the benefit was partial [40]. Clinicians consistently describe the goal as stopping progression, not reversing damage already done. That is why "earlier is better" is said so often, and why families are told to keep skills in daily use while they wait.