Metachromatic leukodystrophy Trials in Disease

Study of Atidarsagene Autotemcel for Treating Early Onset Metachromatic Leukodystrophy (MLD) in Patients

This trial is testing a gene therapy treatment called OTL-200 (also known as Libmeldy) for early onset forms of the condition. The treatment uses the patient's own cells, which are collected and then genetically modified to produce the missing enzyme that causes the disease.

Who can participate: The trial is looking for patients with a confirmed diagnosis based on low enzyme activity and genetic testing. Eligible patients include those who have an older sibling with the condition who developed symptoms by age 6, or children diagnosed early (such as through newborn screening) who are 6 years old or younger and have not yet shown symptoms.

Who cannot participate: The trial does not list specific exclusion criteria, but participants must meet all the inclusion requirements and be able to safely undergo the treatment procedures.

What the trial involves: The main goal is to evaluate how well the gene therapy works in treating early onset forms. The treatment is given through a single intravenous infusion, meaning it is delivered directly into the bloodstream. After receiving the therapy, participants will be followed for 24 months with regular assessments of their motor function, neurological health, and overall safety. The study will also monitor for any side effects and check whether the treatment helps maintain or improve movement abilities.

Treatment being tested: OTL-200 is a one-time gene therapy that introduces a working copy of the ARSA gene into the patient's cells, allowing the body to produce the enzyme it lacks.

Study of Intrathecal Cebsulfase Alfa for Children with Late Infantile Metachromatic Leukodystrophy

This trial is testing an enzyme replacement therapy called cebsulfase alfa (also known as SHP611) for children with the late infantile form of the condition. Unlike gene therapy, this treatment replaces the missing enzyme directly.

Who can participate: Children with a confirmed diagnosis of late infantile form are eligible. They must have documented low enzyme activity and high levels of specific fats in their urine. Participants need to have movement problems confirmed by a doctor by 30 months of age, or show early symptoms within specific age ranges depending on their group. The patient's age at enrollment must be between 6 to 72 months, depending on which study group they join.

Who cannot participate: Children who do not have a confirmed diagnosis, are outside the specified age ranges, have already lost the ability to move independently, or are part of a vulnerable population requiring special protection cannot participate.

What the trial involves: The main goal is to see if the treatment can delay the loss of movement abilities compared to untreated patients. The medication is delivered directly into the spinal fluid through repeated injections over the course of the study. Participants will be monitored until Week 106 with regular assessments of motor function, language abilities, and overall safety. The treatment aims to reduce the buildup of harmful fats in the nervous system.

Treatment being tested: Cebsulfase alfa is an enzyme replacement therapy that provides the missing enzyme directly to the central nervous system through spinal injections.

Study on Gene Therapy with Atidarsagene Autotemcel for Patients with Metachromatic Leukodystrophy

This trial is studying another gene therapy approach using Libmeldy (atidarsagene autotemcel) for patients who have not yet shown symptoms or are in the very early stages of the disease.

Who can participate: The trial is open to patients who are either pre-symptomatic late infantile patients or pre- to early-symptomatic early juvenile patients. This means they have the genetic diagnosis but either have no symptoms yet or are just beginning to show mild symptoms. Parents or guardians must provide informed consent for children to participate.

Who cannot participate: Patients with other serious health conditions that could interfere with the study, those unable to follow study procedures, anyone with previous treatments that might affect results, patients currently in another trial, those with allergies to study substances, pregnant or breastfeeding individuals, those with a history of substance abuse, mental health conditions affecting participation, active infections, or blood disorders cannot join.

What the trial involves: The study aims to evaluate both safety and effectiveness of the gene therapy in preventing or slowing disease progression. After participants receive the modified cells through an intravenous infusion, they will be monitored for up to 36 months. The study will measure improvements in motor function using standardized scales, with the goal of seeing at least a 10% improvement. Additional assessments include nerve function tests, brain imaging, and intelligence testing.

Treatment being tested: This hematopoietic stem cell gene therapy modifies the patient's own stem cells to correct the genetic defect, then infuses them back into the patient to restore enzyme production.

Study on Long-Term Safety and Efficacy of Cebsulfase Alfa for Children with Late Metachromatic Leukodystrophy Receiving Intrathecal Enzyme Replacement

This is a long-term follow-up study for children who previously participated in an earlier trial testing HGT-1110 (cebsulfase alfa). It focuses on gathering information about the treatment's safety and effects over an extended period.

Who can participate: Only patients who completed the earlier Study HGT-MLD-070 through Week 40 are eligible. They must not have any safety or medical issues that would prevent continued participation. Written consent from parents or legal representatives is required before any study activities begin.

Who cannot participate: Anyone who did not participate in the previous study through Week 40 cannot join this extension study.

What the trial involves: The study continues the enzyme replacement therapy with regular injections into the spinal fluid. Participants will be monitored for any side effects through laboratory tests, vital signs checks, and physical examinations. The study will also check for antibodies against the treatment in both spinal fluid and blood. Effectiveness will be measured through motor function assessments, adaptive behavior evaluations, and caregiver observations. The concentration of the medication in the spinal fluid will also be measured at selected time points.

Treatment being tested: HGT-1110 (cebsulfase alfa) is an enzyme replacement therapy delivered directly into the spinal canal to reach the central nervous system effectively.

Study on the Effects of Atidarsagene Autotemcel for Patients with Late Juvenile Metachromatic Leukodystrophy

This trial is testing gene therapy specifically for the late juvenile form of the condition, which typically appears in older children and progresses more slowly than earlier forms.

Who can participate: Patients must have a confirmed diagnosis with specific genetic features associated with the late juvenile variant. If they have symptoms, these must have started between ages 7 and 16. If they do not yet have symptoms, they must be under 17 years old and have a sibling with the late-juvenile form. Eligible patients must have normal thinking abilities (IQ score of 85 or higher) and either normal movement skills for their age (if under 7) or the ability to walk independently or with only mild difficulties (if 7 or older). Patients or their guardians must agree to follow birth control requirements if applicable and sign consent forms.

Who cannot participate: Patients with other serious medical conditions, recent infections, those taking interfering medications, anyone with allergic reactions to similar treatments, those unable to follow procedures, pregnant or breastfeeding individuals, recent participants in other trials, those with substance abuse history, certain genetic conditions, or recent/planned surgeries cannot participate.

What the trial involves: The study aims to observe how a single infusion of the gene therapy affects the disease, particularly looking at changes in enzyme activity in the cerebrospinal fluid and brain. Participants will undergo baseline assessments before receiving the treatment through an intravenous infusion. After treatment, they will be monitored for 24 months and beyond, with regular assessments of health markers, enzyme levels, cognitive function, and motor abilities. The study will also monitor for any adverse effects.

Treatment being tested: OTL-200 (Libmeldy) is a gene therapy that delivers a functional copy of the ARSA gene to restore enzyme production, given as a single infusion.

Summary

These five clinical trials represent important research efforts to find effective treatments for different forms of Metachromatic Leukodystrophy. The trials use two main approaches: gene therapy (using modified versions of patients' own cells to correct the genetic problem) and enzyme replacement therapy (providing the missing enzyme directly through spinal injections).

Italy is notably active in this research, hosting trials for all three gene therapy studies. Several countries including France, Germany, Belgium, Spain, Greece, Czechia, and Denmark are participating in the enzyme replacement therapy studies, showing strong European collaboration in researching this rare condition.

The trials target different patient groups based on age and disease progression, from very young children diagnosed before symptoms appear to older children with the late juvenile form. This comprehensive approach offers potential treatment options for various stages and types of the disease.

Patients interested in participating should discuss these options with their medical team to determine which trial, if any, might be appropriate for their specific situation.