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Testing Gene Therapy AAV9/AP4M1 in Patients with Hereditary Spastic Paraplegia Type 50

Verified siteInvestigationalNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study involves Hereditary Spastic Paraplegia Type 50, also known as SPG50, which is a rare inherited condition that affects movement and causes muscle stiffness and weakness, particularly in the legs. The condition is caused by changes in a specific gene called AP4M1. The treatment being tested is called Melpida, which is a type of gene therapy designed to deliver a working copy of the AP4M1 gene to the body. This therapy uses a modified virus called adeno-associated virus type 9, or AAV-9, which acts as a delivery vehicle to carry the correct gene into cells. The treatment is given as a single dose through intrathecal administration, which means it is injected into the space around the spinal cord in the lower back.

The purpose of this study is to determine whether this single dose of gene therapy can improve the condition of people with SPG50. The study will measure changes in motor function, which refers to the ability to move and control muscles, by looking at major movement milestones such as sitting, standing, and walking. During the study, participants will receive the treatment and then be followed for several years to observe any improvements in their movement abilities, overall development, and quality of life. The study will also look at markers in the blood and cerebrospinal fluid, which is the liquid that surrounds the brain and spinal cord, to understand how the disease and treatment affect the nervous system.

Participants will need to attend regular visits at the study center over a period of several years after receiving the treatment. These visits will include various assessments to measure movement skills, thinking abilities, and overall wellbeing. For safety reasons, participants must stay within a reasonable distance from the study center for the first month after treatment so they can quickly return if needed. The study will track how participants respond to the treatment by comparing their abilities before and after receiving the gene therapy, with the main assessment taking place about three years after treatment.

The research process

The trial runs in 10 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Treatment administration

    You will receive a single dose of Melpida, which contains the active substance melpida. This is an experimental gene therapy designed to deliver a corrected version of the gene that is altered in Hereditary Spastic Paraplegia Type 50.

    The medication will be administered as a solution for injection directly into the space around your spinal cord. This method is called intrathecal administration and is performed through a lumbar injection in the lower back area.

    This is a single administration, meaning you will receive the treatment only once during the entire study.

  2. Step 2

    Immediate post-treatment period

    During the first 30 days after receiving the treatment, you must stay at a location that allows you to reach the clinical site within approximately 90 minutes. This corresponds to a maximum distance of about 150 kilometers from the site.

    This requirement is in place for safety reasons, to ensure rapid access to medical care if needed.

  3. Step 3

    Follow-up assessments

    You will attend scheduled study visits throughout the trial period. The total duration of your participation in the study will be 156 weeks, which is approximately 3 years.

    During these visits, various assessments will be performed to evaluate how the treatment affects your condition.

  4. Step 4

    Motor function evaluations

    Your motor abilities will be assessed using the Gross Motor Function Measure, known as GMFM-88. This test evaluates major motor skills and movements.

    The focus will be on measuring changes in your ability to perform eight major motor milestones compared to your abilities at the start of the study.

    Additional evaluations will measure both gross motor skills, which involve large movements like walking or sitting, and fine motor skills, which involve smaller, precise movements.

  5. Step 5

    Cognitive and developmental assessments

    Your cognitive abilities will be evaluated using the Bayley Scale of Infant and Toddler Development, 3rd Edition, which assesses thinking and learning skills.

    Additional cognitive testing will be performed using the Differential Ability Scales, 2nd Edition.

    Your adaptive behavior and developmental progress will be measured using Developmental Quotients and the Vineland Adaptive Behavior Scale, 3rd Edition. These assessments evaluate how you perform everyday activities and skills appropriate for your age.

  6. Step 6

    Disease severity monitoring

    The severity of your condition will be monitored using the Spastic Paraplegia Rating Scale, which specifically measures symptoms related to spastic paraplegia.

    Your physician will assess overall changes in your condition using the Clinical Global Impression scale.

    Your primary caregiver will also provide their assessment of changes in your condition using the Parent-rated Global Impression scale.

  7. Step 7

    Biological marker testing

    Blood samples will be collected to measure neurofilament light chain levels in your plasma. Neurofilaments are proteins released when nerve cells are damaged, so measuring them helps assess nerve damage.

    Samples of cerebrospinal fluid, the fluid surrounding your brain and spinal cord, will also be collected to measure neurofilament light chain levels.

    Additional biological markers in your blood and cerebrospinal fluid will be measured to evaluate the effects of the treatment.

  8. Step 8

    Quality of life assessment

    Your caregiver will complete the Caregiver Priorities and Child Health Index of Life with Disabilities questionnaire. This assessment measures health-related quality of life from the caregiver's perspective.

  9. Step 9

    Contraception requirements

    If you are sexually active, you must use highly effective contraceptive methods throughout the entire 5-year study period.

    Additionally, you must use a barrier method of contraception for 6 months after receiving the treatment, regardless of any other contraceptive method you are using.

    This requirement applies to all sexually active participants, regardless of sexual orientation.

  10. Step 10

    Medication stability

    If you are taking any medications for related symptoms, such as medications for muscle stiffness, seizures, behavior management, sleep problems, or following special diets or nutritional support, you should maintain stable doses throughout the study.

    Any changes to these medications during the study should be discussed with the study physician.

Who can join the trial?

9 criteria

  • The patient must be male or female and at least 6 years old at the time of screening.
  • The patient must have a confirmed diagnosis of SPG50, which means they have specific changes in both copies of the AP4M1 gene. This diagnosis must be confirmed through genetic testing performed in a certified laboratory.
  • The patient must be able to sit independently for three seconds without support.
  • The patient must show signs of neurological dysfunction, meaning there are problems with how the nervous system works, based on their medical history and physical examination.
  • The patient must be on stable doses of any medications they are taking, including medicines for muscle stiffness, seizures, behavior, sleep, as well as special diets, supplements, or nutritional support. These doses should not have changed for at least three months before screening.
  • The patient must have two legally competent parents or legal representatives who can provide informed consent, or one parent with sole legal authority who can actively participate in the consent process.
  • The legal representatives must be able to attend all scheduled study visits and provide information about the patient's symptoms and how they are doing.
  • The patient and caregivers must be able to travel to the study center. For 30 days after treatment, the patient must live in a location that allows them to reach the clinical site within approximately 90 minutes, which is about 150 kilometers from the site.
  • Any sexually active patient must be willing to use highly effective birth control methods for the full 5 years of the study and use a barrier method of birth control, such as condoms, for 6 months after receiving the treatment.

Who cannot join the trial?

3 criteria

  • The study does not list specific exclusion criteria in the provided information, meaning details about who cannot participate are not available in this document
  • Generally, clinical trials may exclude patients based on certain health conditions, previous treatments, or other medical factors, but these specific details are not provided here
  • If you are considering participation, the research team would need to review your complete medical history to determine if you meet all requirements
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Investigated drugs

AAV9/AP4M1 is an experimental gene therapy given as a single injection into the spinal fluid through the lower back. It is being tested as a potential treatment for people with a rare inherited condition called Hereditary Spastic Paraplegia Type 50 (SPG50), which affects movement and muscle control. This therapy is designed to deliver genetic material to help correct the underlying cause of the disease.

What is already known about the treatment

AAV9/AP4M1 – This is an experimental gene therapy product administered as a single injection into the spinal fluid through the lower back (lumbar intrathecal injection). It is currently being studied in clinical trials and is not yet approved for general medical use. This treatment is being developed specifically for patients with Hereditary Spastic Paraplegia Type 50 (SPG50), a rare genetic disorder that causes progressive muscle stiffness and weakness in the legs. The therapy works by using a modified virus (AAV9) as a delivery vehicle to introduce a working copy of the AP4M1 gene into cells, which helps restore the missing or faulty protein that causes the disease.

Investigated diseases

Hereditary Spastic Paraplegia Type 50 – Hereditary Spastic Paraplegia Type 50 is a rare genetic disorder that affects the nervous system and movement abilities. The condition is caused by mutations in a specific gene that leads to problems with nerve cell function in the brain and spinal cord. Children with this disease experience progressive difficulties with muscle control and movement development. The main features include muscle stiffness, particularly in the legs, and weakness that worsens over time. Motor skills such as sitting, standing, and walking are significantly delayed or impaired. The disease also affects cognitive development and adaptive behaviors in daily life activities.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IITrial ID2025-522603-15-00Protocol codeAAV9/AP4M1-ITA-01Estimated enrolment5 patientsSponsorAzienda Socio Sanitaria Territoriale Papa Giovanni Xxiii

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