A snapshot of what is confirmed as of 20 October 2026, checked against ClinicalTrials.gov, PubMed and the organisations’ own pages. Numbers in brackets refer to the research page source list.
SPG50 gene therapy, Phase 3. The MELPIDA Phase 3 trial (NCT06692712) started on 1 April 2026 at UT Southwestern in Dallas and Sant Joan de Déu in Barcelona. It treats about eight children with SPG50 aged 4 to 72 months and follows about sixteen untreated concurrent controls, who may have SPG47, SPG50 or SPG52. The primary endpoint is measured at 156 weeks; estimated primary completion is February 2032 [31]. LifeArc announced a partnership with the sponsor in May 2026 and states the aim of FDA approval by early 2028; that is an aim, not a regulatory commitment [46]. An Italian investigator-led Phase II trial is listed in the EU register with a September 2026 start [47].
SPG47 gene therapy. The FDA cleared the trial application in May 2025 [58]. The trial (NCT06948019) is registered at Boston Children’s Hospital and remains “not yet recruiting”; Cure AP-4 states recruitment may begin once funding is secured [32, 37].
SPG52 gene therapy. The Barcelona program at UAB remains preclinical. Its last public milestones are the December 2024 results announcement and the May 2025 update that the safety and toxicology phase had begun [25, 26]. No peer-reviewed publication, no trial application, no registered trial. The program’s official page is micromecenatge.uab.cat/terapiagenicaparaplegia. See gene therapy for SPG52 for the full picture, including why funding is still needed.
The ATG9A ratio. A 2026 paper from the Boston group describes the ATG9A ratio in patient skin cells as a functional test that can confirm or reclassify uncertain AP-4 variants in about four to six weeks, and positions it as relevant to trial eligibility [8]. It is a research assay, not yet a certified clinical test.
New drug targets. A 2026 CRISPR screen in a neuronal model of AP-4 deficiency identified two genes whose loss frees ATG9A from the Golgi, one flagged as a candidate for therapeutic investigation [38]. The Boston small-molecule lead reaches the brain in early animal work but clears quickly; work continues on potency and exposure [9, 37].
The registry. The Boston registry (NCT04712812) is recruiting to 2030 and held nearly 600 patients in October 2025 [9, 60]. If your child is not in it, that is the single most useful step this month. Contact details are on the first 90 days page.