- **uniQure's AMT-130 for Huntington's disease** demonstrated a **75% statistically significant slowing of disease progression** based on composite UHDRS and total functional capacity in 45 patients with three years of follow-up data.  **[0001735438_2194098_1]**  The company expects a **pre-BLA meeting in Q4** and **BLA submission in Q1 next year**.  **[0001735438_2194098_1]** 
- **MeiraGTx Holdings' Parkinson's program** has shown **three positive studies and two positive studies UPDRS against SHAM**, with AI analysis of FDG PET scans indicating **physiological changes in the brain**.  **[0001735438_2194098_0]**  The company is using AI to enhance the robustness of its primary endpoint in its pivotal study.  **[0001735438_2194098_4]** 
- **Passage Bio's lead clinical program for frontotemporal dementia (FTD) with GRN mutation** has demonstrated **high durable levels of target engagement of CSF progranulin** and **stabilization of plasma neurofilaments**, with more data expected next year.  **[0001735438_2194098_2]** 
- Panelists emphasized that **local delivery of gene therapies** and **lower doses** contribute to **improved safety profiles** by reducing systemic exposure and the risk of inflammatory responses, which is a key advantage for neurodegenerative diseases.  **[0001735438_2194098_6]** 
- Regulatory agencies, particularly the FDA, are showing **increased flexibility for rare diseases with high unmet needs**, including openness to **single-arm studies with supportive evidence** and the use of **biomarkers** to assess effectiveness, which is crucial for gene therapies in slow-progressing neurodegenerative conditions.  **[0001735438_2194098_7]**

Genetic Medicines Companies Discuss Neurodegenerative Disease Programs and Regulatory Landscape

- **MGTX (MIRA)** reported positive Phase 2 data for its Parkinson's gene therapy, demonstrating physiological brain changes and neuroprotective effects, and is leveraging AI technology to enhance its pivotal study design with FDA acceptance.  **[0001735438_2194119_0]** **[0001735438_2194119_4]** 
- **UniCure** announced compelling Phase 1/2 data for its Huntington's disease gene therapy, AMT-130, showing a **75% statistically significant slowing of disease progression** over three years, and anticipates a pre-BLA meeting in Q4 2025 and BLA submission in Q1 2026.  **[0001735438_2194119_1]** 
- **Passage Bio** provided an update on its lead clinical program for Frontotemporal Dementia (FTD), which has shown high durable levels of target engagement and stabilized plasma neurofilaments, with further data expected next year.  **[0001735438_2194119_2]** 
- A key strategy across these companies for neurodegenerative gene therapies is **local delivery** and the use of **lower doses** to mitigate systemic safety risks and immune responses, a critical consideration given recent safety events in the sector.  **[0001735438_2194119_6]** 
- The panelists emphasized the **FDA's increasing flexibility** in regulatory pathways for rare neurodegenerative diseases, including openness to novel trial designs, biomarkers, and external controls, which could expedite product development and approval.  **[0001735438_2194119_3]** **[0001735438_2194119_7]** **[0001735438_2194119_8]**

MeiraGTx Holdings (MGTX)