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Not yet recruitingRare disease

Safety and tolerability of intracisternal GNT0009 gene therapy plus drug combination in patients with spinal muscular atrophy with progressive myoclonic epilepsy (SMA‑PME)

Verified siteRegistered drugNo placebo
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What is this trial about?

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

The study focuses on Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy, a rare genetic disorder that causes muscle weakness and seizures. Participants will receive a one‑time treatment called GNT0009, which is a type of gene therapy using a harmless virus known as AAV9 to deliver a normal copy of the ASAH1 gene directly into the fluid around the brain and spinal cord (intracisterna magna). This approach aims to provide the missing enzyme that is lacking in the disease.

The main goal of the trial is to see whether the single administration of the therapy is safe and well tolerated. After the injection, participants will attend regular check‑ups over many months, during which doctors will monitor vital signs, blood tests, and any side effects. They will also evaluate how well participants can move (motor function), breathe (respiratory assessments), think and learn (cognitive assessments), hear, and overall quality of life.

Throughout the study, participants will continue any standard medicines they already use, and the research team will keep track of any health changes for up to several years to ensure long‑term safety.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Enrollment and Baseline Evaluation

    After joining the study, you will undergo a comprehensive baseline assessment. This includes physical examinations, vital‑sign measurements, laboratory tests, and documentation of your medical history related to spinal muscular atrophy with progressive myoclonic epilepsy (SMA‑PME).

    Baseline data are collected to compare future results and to ensure you meet the study criteria.

  2. Step 2

    Single Intracisterna Magna Gene‑Therapy Infusion

    You will receive a one‑time infusion of rAAV9‑hASAH1 (also referred to as GNT0009) directly into the intracisterna magna, a fluid‑filled space near the brain. The infusion is performed by a qualified physician using a sterile solution for infusion.

    The purpose of this gene‑therapy infusion is to deliver a functional copy of the human ASAH1 gene to your nervous system.

  3. Step 3

    Background Medication Regimen

    Following the gene‑therapy infusion, you will continue taking several background medications that support your overall health and help manage the disease. The medications and their routes of administration are:

    Prednisone – oral route.

    Prednisolone – oral route.

    Natalizumab – intravenous infusion.

    Eculizumab – intravenous infusion.

    Tacrolimus – oral route.

    Antihistamines for systemic use – oral route.

    Methylprednisolone acetate with lidocaine – intravenous infusion.

    Rituximab – intravenous infusion.

    Specific doses, frequency, and duration will be determined by your treating physician and are tailored to your individual needs.

  4. Step 4

    Early Safety Monitoring (First Week)

    During the first week after the infusion, you will be closely monitored for any immediate adverse events. This includes daily checks of vital signs, observation for signs of infection or allergic reaction, and laboratory tests to evaluate blood clotting (including D‑dimer) and other safety parameters.

  5. Step 5

    Scheduled Follow‑Up Visits

    You will attend follow‑up visits at approximately week 4, week 12, week 24, and week 48. At each visit, the study team will perform:

    • Physical examination and vital‑sign measurement.

    • Laboratory testing to detect any abnormal results.

    • Assessment of motor function, respiratory status, cognitive abilities, adaptive skills, hearing, and overall neurological condition.

    • Completion of a quality‑of‑life questionnaire.

    These assessments help determine the safety, tolerability, and potential clinical benefit of the gene therapy.

  6. Step 6

    Long‑Term Safety Monitoring (Up to 60 Months)

    After the week‑48 visit, you will continue to be monitored for up to five years (60 months) to identify any late‑occurring adverse drug reactions or malignancies. Periodic check‑ins may include phone calls, clinic visits, or laboratory tests as directed by the study physician.

Who can join the trial?

6 criteria

  • Be a male or female participant (any gender is accepted).
  • Have a confirmed genetic diagnosis of Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA-PME) – this means a lab test has identified the specific gene changes that cause this condition.
  • Have up‑to‑date immunizations (vaccinations) according to the French national schedule for 2025, which includes the recommended shots for your age or risk group such as hepatitis B, measles‑mumps‑rubella (MMR), chickenpox (varicella), hepatitis A (if at risk), meningococcal disease (caused by Neisseria meningitidis, types ACWY + B), pneumonia (caused by Streptococcus pneumoniae), seasonal flu, COVID‑19 (caused by SARS‑CoV‑2), and respiratory syncytial virus (RSV) when advised.
  • Be able, or have a legal representative who can, confirm that you will follow the study’s visit schedule and all required procedures.
  • Use an effective method of contraception (a reliable way to prevent pregnancy) throughout the study period.
  • Be at least 2 years old.

Who cannot join the trial?

11 criteria

  • You have been diagnosed with Farber disease (a rare disorder that causes painful lumps under the skin and joint problems).
  • You have a positive test for HIV (human immunodeficiency virus) or an active hepatitis B or hepatitis C infection (liver infections).
  • You are currently taking medicines that strongly affect the enzymes CYP3A4 or the protein P‑glycoprotein (P‑gp), which can change how the study drug works.
  • You have a severe intellectual disability, meaning an IQ score lower than 50.
  • You have a GMFC‑MLD score of 6, which means you cannot move around at all and have lost control of your head and trunk.
  • You have another serious medical condition or abnormal test results that the doctor believes could make the study unsafe or affect the disease.
  • You have moderate to severe liver problems (grade 3 or higher) according to standard safety grading (hepatic dysfunction Grade ≥3).
  • Your lung function is very poor (forced vital capacity FVC less than 30% of what is expected) or you need a breathing machine for most of the day or have a tube in your neck for ventilation.
  • You have had high pressure inside the skull, fluid buildup called hydrocephalus, or have needed a procedure to drain brain fluid (increased intracranial pressure or need for CSF diversion).
  • You have a bleeding disorder or abnormal blood‑clotting tests that raise the risk of bleeding from the spinal injection (coagulation disorders).
  • You have permanent metal implants or devices that are not safe for MRI scans, such as metal braces (non‑MRI‑compatible implants).
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Investigated drugs

  • PREDNISOLONE

    is an oral steroid medication given to patients in the study to lower inflammation and calm an over‑active immune system. It helps reduce swelling and can lessen symptoms that are caused by the body’s immune response.

  • Prednisone

    is another oral steroid used as background therapy. Like other steroids, it works by suppressing inflammation and the immune reaction, which can help control disease‑related symptoms.

  • Natalizumab

    is given by IV infusion. It is a monoclonal antibody that blocks certain immune cells from entering the brain and spinal cord, helping to reduce harmful immune activity that can worsen neurological problems.

  • Eculizumab

    is an IV medication that blocks a part of the immune system called the complement system. By stopping this pathway, it helps prevent damage caused by an overactive immune response.

  • Tacrolimus

    is taken by mouth and works as an immunosuppressant. It reduces the activity of immune cells, which can help keep the immune system from attacking the body’s own tissues.

  • Antihistamines for systemic use

    are oral medicines that calm allergic reactions and can lessen itching or other histamine‑related symptoms that might appear during the trial.

What is already known about the treatment

  • Betamethasone sodium phosphate

    This drug is taken orally as a tablet or liquid. It is a synthetic steroid that is well known in medical literature for reducing inflammation and calming an over‑active immune system. It is used for allergic reactions, asthma, skin inflammation, and other inflammatory conditions. The medication works by entering cells, binding to steroid receptors, and switching off genes that produce inflammatory chemicals.

  • Prednisone

    Prednisone is taken by mouth in tablet form. It is a widely used corticosteroid that helps lower swelling and suppresses immune responses, and it appears in many clinical guidelines. Doctors prescribe it for autoimmune diseases, asthma, and severe allergies. Inside the body it is converted to the active form prednisolone, which binds to cell receptors and blocks the production of inflammatory signals.

  • Prednisolone

    Prednisolone is an oral tablet that acts as an anti‑inflammatory and immune‑modulating agent. It is a standard medication listed in textbooks for treating conditions such as rheumatoid arthritis, lupus, and severe asthma. The drug works by attaching to steroid receptors inside cells and turning off genes that cause inflammation. Its effects are similar to other steroids but it is already active, so it works quickly after swallowing.

  • Natalizumab

    Natalizumab is given by intravenous infusion, usually in a hospital setting. It is an approved biologic that targets a specific protein on white blood cells, preventing them from entering the brain and spinal cord. The medication is used mainly for multiple sclerosis and Crohn’s disease. By blocking this protein, it reduces inflammation and damage caused by immune cells in the nervous system.

  • Eculizumab

    Eculizumab is administered through an intravenous infusion. It is a monoclonal antibody that is approved for rare blood‑cell disorders and some kidney diseases. The drug works by binding to a part of the complement system, a series of proteins that can cause harmful inflammation, and stops that cascade from activating. This helps protect cells from being damaged by the immune system.

  • Tacrolimus

    Tacrolimus is taken orally as a capsule or tablet. It is a well‑known immunosuppressant used to prevent organ rejection and to treat certain skin conditions. The medication blocks a key enzyme inside immune cells, which stops them from becoming active and reduces inflammation. Its use is supported by many clinical studies and treatment guidelines.

Investigated diseases

Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) - Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a rare genetic disorder that combines muscle weakness due to loss of motor neurons with episodes of sudden muscle jerks (myoclonus) and seizures. The condition usually begins in childhood, with gradual loss of motor abilities such as walking and crawling. Over time, the myoclonic seizures become more frequent and may spread to involve the whole body. As the disease progresses, respiratory muscles can become weak, making breathing more difficult.
Trial detailsLast updated 11 Nov 2026
Age0-17PhasePhase ITrial ID2026-527323-10-00Protocol codeGNT-022-ASAHEstimated enrolment3 patientsSponsorGenethon

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