In short
Melpida is an investigational gene therapy being studied for hereditary spastic paraplegia type 50 (SPG50), a rare inherited neurological condition. Three clinical trials are currently authorised in the EU, including one Phase 3 trial with 24 participants and two Phase 2 trials with 5 and 2 participants respectively. Melpida has no marketing authorisation and is given as a single intrathecal injection.
Key points
- Melpida is an investigational gene therapy for hereditary spastic paraplegia type 50 (SPG50).
- It is delivered as a single intrathecal injection into the fluid around the spinal cord.
- The largest trial is a Phase 3 study with 24 participants.
- Two smaller Phase 2 trials include 5 and 2 participants respectively.
- The main measure is change in motor milestones on the GMFM-88 scale at week 156.
- Melpida received orphan drug designation from the FDA in 2022.
What is melpida?
Melpida is an investigational gene therapy being developed for hereditary spastic paraplegia type 50 (SPG50), a rare inherited condition that affects the nervous system and causes progressive weakness and stiffness in the legs. The substance is described in registry records as a structurally diverse substance and is supplied as a solution for injection. Melpida has no marketing authorisation in the product records, meaning it is still under investigation and not approved as a medicine. The product is supplied by Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII.
The US Food and Drug Administration (FDA) describes melpida as a self-complementary adeno-associated virus 9 (AAV9) gene therapy containing a codon-optimised human AP4M1 gene. In 2022, the FDA granted melpida orphan drug designation for the treatment of patients with SPG50 caused by mutations in the AP4M1 gene. Orphan designation is a status given to treatments for rare diseases that provides incentives for development.
How does melpida work?
Melpida is designed to deliver a working copy of the AP4M1 gene to cells using a modified virus called AAV9 as a carrier. In SPG50, mutations in the AP4M1 gene mean the body cannot produce a protein needed for normal nerve cell function. The gene therapy aims to introduce a corrected version of the gene so that cells can produce the missing protein. The trial summaries state that a single lumbar intrathecal administration of AAV9/AP4M1 is used, meaning the therapy is injected into the fluid-filled space around the lower spinal cord.
Which conditions is melpida used or studied for?
Melpida is studied exclusively for one condition:
- Hereditary spastic paraplegia type 50 (SPG50) — a rare inherited neurological disorder caused by mutations in the AP4M1 gene, leading to progressive motor difficulties.
How is melpida given?
Melpida is given as a solution for injection by the intrathecal route, which means it is injected directly into the fluid surrounding the spinal cord. In the trials, a single lumbar intrathecal administration is used, delivered in the lower back area.
What do the clinical trials show?
Three clinical trials of melpida in SPG50 are authorised in the EU Clinical Trials Information System. All are interventional studies and all are currently authorised.
What phases and status do the trials have?
The largest trial is a Phase 3 efficacy study with a concurrent control, enrolling 24 participants. Two Phase 2 trials are also authorised: one with 5 participants and one with 2 participants. The Phase 3 trial also lists several other medicines as interventions, including paracetamol, prednisone, methylprednisolone, tacrolimus, sirolimus, diphenhydramine and gadoteric acid, which are given as part of the treatment regimen.
What are the trials measuring?
All three trials measure change in motor milestones using the Gross Motor Function Measure (GMFM-88), a standard tool for assessing movement abilities. The primary outcome in the Phase 2 trials is the change in total percent score of eight major motor milestones derived from the GMFM-88 from baseline at week 156. The Phase 3 trial uses a similar measure: eight motor milestone achievements scored on a 2-point scale, with week 156 change from baseline in the trajectory of the eight major milestones total score as the primary outcome.
Who can take part in these trials?
The trials enrol people affected by hereditary spastic paraplegia type 50 (SPG50). The Phase 3 trial has the largest planned enrolment with 24 participants. The Phase 2 trials are smaller, with 5 and 2 participants respectively. Detailed eligibility criteria are available in the individual trial records.
What side effects are known?
The supplementary sources provided do not include specific information about side effects of melpida. The trials are designed to assess safety as well as efficacy, and the Phase 3 study states that its objective is to determine the safety and efficacy of melpida in subjects with SPG50.
Ongoing research and future directions
Melpida is the subject of active clinical development. A case study published in 2025 describes the development of melpida by Elpida Therapeutics, highlighting the role of patient advocacy in advancing research for this rare condition. The FDA granted orphan drug designation in 2022, and the therapy is not yet approved for any indication. The authorised trials in the EU represent the current clinical research programme for this investigational gene therapy.