Rare Disease Day 2026: The Latest Updates in Rare Neurological Disease Therapy

Since 2008, February 28 has been observed as Rare Disease Day by the patient and clinician communities. Intended to honor those with rare diseases of all varieties, Rare Disease Day was established by by the European Organisation for Rare Diseases, but has been celebrated worldwide since 2009, when the National Organization for Rare Disorders helped to get advocacy groups in the United States—and eventually other regions of the globe—to observe the day.

NeurologyLive^® regularly covers news related to rare diseases that fall under the umbrella of Neurology, and partners with a number of rare disease advocacy organizations, including the ALS Association, Cure SMA, the Dravet Syndrome Foundation, the Lennox-Gastaut Syndrome Foundation, and the TSC Alliance, with the aim of increasing awareness and informing clinicians about the latest advances in therapeutic development and care for these rare and often challenging-to-treat disorders. This year for Rare Disease Day, the NeurologyLive team has put together a roundup of our latest news and interviews in several rare neurological diseases. Click the links below each item to read more.

The Aging LGS Patient: Reassessing Diagnosis, Treatment, and Outcomes

In this NeurologyLive® Special Report video program, Joseph Sullivan, MD, the director of the Pediatric Epilepsy Center of Excellence at the University of California San Francisco, discussed key considerations in the transition of care from pediatric to adult epilepsy management. In this fifth and final episode, Sullivan highlighted how Lennox-Gastaut syndrome (LGS) evolves from early childhood into adulthood and emphasized the role of adult epilepsy providers in continuing care. He stressed the importance of identifying the genetic or etiological basis of LGS to guide precision medicine approaches, rather than relying solely on broad-spectrum anti-seizure medications. Sullivan also discussed the value of revisiting prior treatments, such as valproic acid, to optimize outcomes and improve quality of life for patients, acknowledging that seizure types and their impact can change over time.

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The Role of Genetic Testing in Dravet Syndrome

This segment explores the critical role of genetic testing in the early identification and management of Dravet syndrome. Dr. Joseph Sullivan emphasizes that broader access to genetic testing has enabled earlier referrals and more informed clinical conversations, helping clinicians avoid contraindicated medications and develop appropriate care plans sooner. He notes, however, that access remains uneven and delays still occur across the healthcare system. The discussion highlights that a small but important subset of patients may test negative for SCN1A mutations despite having a clinical presentation consistent with Dravet syndrome, underscoring the need for continued clinical suspicion and referral to specialized centers.

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DMD Gene Therapy Elevidys Shows Functional Benefit at 2 Years in Phase 3 EMBARK Trial

Two-year data from the phase 3 EMBARK clinical trial (NCT05096221) suggest that treatment with delandistrogene moxeparvovec (marketed as Elevidys) was associated with stabilization or slowing of functional decline in ambulatory children with Duchenne muscular dystrophy (DMD), compared with a matched external control cohort receiving standard-of-care corticosteroids. Improvements in motor function measures including the North Star Ambulatory Assessment (NSAA), time to rise (TTR), and 10-meter walk/run (10MWR) were observed over 104 weeks, supporting the durability of the microdystrophin gene therapy approach.

DMD is a progressive X-linked disorder caused by pathogenic variants in the DMD gene leading to absence of functional dystrophin, resulting in muscle degeneration, loss of ambulation, and premature death from respiratory or cardiac complications. Gene replacement strategies designed to deliver microdystrophin constructs have emerged as disease-modifying approaches.

EMBARK is a phase 3, randomized, placebo-controlled crossover study evaluating Elevidys in ambulatory boys aged 4 to younger than 8 years with DMD. The therapy uses a recombinant adeno-associated virus serotype rh74 vector to deliver a microdystrophin gene to skeletal muscle.

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Microbiome-Targeted Agent PLL001 Passes Safety Check in Phase 1/2 Trial of ALS

In a recent company update, PLL Therapeutics announced positive safety data from a phase 1/2 trial (NCT06513546) testing PLL001, a microbiome-targeted, gut-brain axis therapeutic, in patients with early-stage amyotrophic lateral sclerosis (ALS). All told, the therapy met its primary safety objective and will now proceed to part 2 of the study, where investigators will assess efficacy and next steps.

Part 1 of the study was a randomized, double-blind, single-ascending dose evaluation involving 12 patients with ALS across 3 dose-level cohorts, with 4 subjects per cohort. Within each cohort, participants were randomly assigned 3:1 to receive a single subcutaneous dose of PLL001 or placebo, with placebo safety data pooled across groups.

According to PLL, the agent showed a favorable and tolerably safety profile, with no serious adverse events (SAEs) reported in the phase 1 portion. Led by Susan Mathers, MD, of Monash University in Australia, the early findings also revealed no treatment-emergent adverse events that led to study discontinuation for the participants involved.

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AskBio’s Late-Onset Pompe Disease Gene Therapy AB-1009 Cleared for Phase 1/2 Trial

AskBio’s investigational new drug (IND) application for AB-1009, a gene therapy candidate intended to treat late-onset Pompe disease (LOPD), has been cleared by the FDA.

In light of the IND clearance, AskBio has launched the phase 1/2 AB-1009 PROGRESS-GT LOPD clinical trial (NCT07282847). The company expects that the first patient will be enrolled in “early 2026”.

AskBio noted that AB-1009 also recently received fast track and orphan drug designations from the FDA. The company also stated that Belief BioMed Inc., Genethon, and Duke University collaborated on AB-1009's advancement to the clinical stage.

“This investigational gene therapy is being studied for its potential to address the underlying genetic defect and to explore whether it can increase production of the deficient enzyme in patients with Pompe disease,” Tahseen Mozaffar, MD, the director of the UCI Health ALS & Neuromuscular Center and the principal investigator of the AB-1009 clinical trial program, said in a statement. “Patients receiving gene therapy may reduce reliance on exogenous enzyme replacement. AskBio’s approach leverages its experience in gene therapy development as it seeks to advance treatment options for Pompe disease.”

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What the EC Decision on High-Dose Spinraza Means for SMA Care

The European Commission (EC) recently granted marketing authorization for a high-dose regimen of nusinersen (Spinraza; Biogen), marking a notable regulatory milestone in the treatment landscape for spinal muscular atrophy (SMA). The approval introduces a revised dosing strategy designed to deliver higher drug exposure earlier in treatment, reflecting a growing recognition that preserving motor neurons as early and as robustly as possible may translate into improved long-term outcomes.

Developed by Biogen, the newly approved high-dose regimen is supported by data from the Phase 2/3 DEVOTE program (NCT04089566) and its ongoing extension, as well as emerging real-world and post-approval evidence. In a conversation with NeurologyLive^®, Stephanie Fradette, PharmD, head of neuromuscular development at Biogen, discussed the clinical significance of this EC approval, what the DEVOTE and RESPOND studies reveal about unmet need in SMA, and how these findings may help refine treatment strategies across different SMA phenotypes and prior-therapy settings.

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Preclinical Study Suggests Stem Cell Therapy EN001 and Insulin May Improve Symptoms of Charcot-Marie-Tooth Disease Type 1A

Investigators reported that both EN001 (ENCell), a Wharton’s jelly-derived investigational mesenchymal stem cell therapy, and insulin improved skeletal muscle strength, endurance, and remyelination in preclinical models of Charcot-Marie-Tooth disease type 1A (CMT1A). Presented at the 2025 Peripheral Nerve Society (PNS) Annual Meeting, held May 17-20, in Edinburgh, Scotland, results suggested that the combination of both treatments yielded greater therapeutic benefits.

In this study, researchers assessed the therapeutic potential of EN001 and insulin in models of CMT1A, including S16 and patient-derived iPSC Schwann cells. All told, findings revealed that both agents significantly promoted Schwann cell proliferation and led to improved muscle performance and nerve regeneration in the treated animals. Notably, investigators observed an improvement in benefit with the combination therapy, which also allowed for a reduced insulin dose.

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Taysha Doses First Patient in Pivotal Trial for Rett Syndrome Gene Therapy TSHA-102, Aligns With FDA on BLA Plans

Taysha Gene Therapies has announced its dosing of the first patient in the pivotal phase 3 portion (Part B) of the REVEAL clinical trial (NCT05606614), which is evaluating investigational adeno-associated virus vector-based gene therapy TSHA-102 for the treatment of Rett syndrome.

According to Taysha, the first patient’s dosing took place in the fourth quarter of 2025. Enrollment is ongoing, and the trial is expected to enroll 15 female patients, aged 6 to less than 22 years, in total. The multicenter study will treat patients with a single, intrathecal dose of the gene therapy at 1x10¹⁵ total vector genomes (vg).

Alongside the announcement, Taysha also stated that it has obtained written alignment from the FDA regarding certain plans for a potential biologics license application (BLA) for TSHA-102. Specifically, the alignment relates to the separate, planned clinical trial referred to as ASPIRE (NCT identifier pending). ASPIRE will evaluate TSHA-102 in 3 girls aged 2 to less than 4 years with the same single 1x10¹⁵ total vg dose, scaled for lower brain volume in the included age group, with a focus on safety. Taysha has aligned with the FDA on the use of at least 3 months of data from this trial to support a BLA submission for the gene therapy aimed at an indication including patients aged 2 years and older.

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