What is the mechanism of action of this treatment?

The most common treatments for Spastic Paraplegia, such as the one studied in the MELPIDA trial, involve gene therapy techniques that deliver functional copies of defective genes directly to neuronal cells. This approach aims to restore normal gene function and counteract neuronal loss, which is crucial for maintaining motor function and reducing spasticity. By targeting the underlying genetic cause, these treatments offer a potential for long-term improvement in symptoms and quality of life for patients with Spastic Paraplegia. This matters significantly for patients as it addresses the root cause of the disease rather than just managing symptoms, potentially leading to more effective and lasting therapeutic outcomes.

What side effects are associated with this type of intervention?

Common treatments for Spastic Paraplegia, particularly those involving gene therapy like the MELPIDA trial, can include intrathecal injections of viral vectors to deliver functional genes to neuronal cells. Known side effects of such treatments may include adverse events related to the injection procedure itself, such as headaches, back pain, and potential infection at the injection site. Additionally, there may be immune responses to the viral vector, leading to inflammation or other immune-mediated effects. Other potential side effects could include transient neurological symptoms, such as dizziness or changes in sensation.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Spastic Paraplegia that involve the delivery of a functional AP4M1 cDNA copy to neuronal cells, similar to the MELPIDA trial. However, gene therapy approaches have been explored and approved for other neurological conditions, such as spinal muscular atrophy (SMA) with the approval of onasemnogene abeparvovec (Zolgensma), which delivers a functional copy of the SMN1 gene. This indicates a growing interest and potential in gene therapy for treating genetic neurological disorders.

What other types of research exist?

Promising alternatives to MELPIDA for Spastic Paraplegia patients include: 1) Antisense oligonucleotide therapies targeting specific genetic mutations, which have shown efficacy in other neurodegenerative diseases. 2) Other adeno-associated virus (AAV)-mediated gene therapies that deliver functional copies of defective genes. 3) CRISPR/Cas9-based gene editing therapies, which are being explored for precise genetic corrections. These alternatives are in various stages of research and clinical trials, showing potential for treating genetic disorders similar to Spastic Paraplegia.

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Virus Therapy

Gene Therapy for Spastic Paraplegia

Phase 1 & 2

Recruiting

Led By Susan T. Iannaccone, MD, FAAN

Research Sponsored by Elpida Therapeutics SPC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Confirmed diagnosis of SPG50 disease by genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, confirmed pathogenic variants in the AP4M1 gene

Clinical history or examination features consistent with SPG50 and that include neurologic dysfunction

Must not have

History of bleeding disorder or any other medical condition or circumstance in which lumbar puncture is contraindicated according to local institutional policy

Contraindication to MELPIDA or any of its ingredients

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 60 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests MELPIDA, a gene therapy for patients with SPG50, a severe neurological disorder. MELPIDA aims to deliver a healthy gene to nerve cells to help them function properly and slow down the disease. Gene therapy has shown positive outcomes in treating complex neurological disorders, including amyotrophic lateral sclerosis, Parkinson's disease, and others.

Who is the study for?

Children aged 1-10 with SPG50, a genetic disorder causing paralysis and intellectual disability. They must be able to take steps independently or with help, stand for over 5 seconds, and have a confirmed AP4M1 gene mutation. Excluded are those on certain medications, unable to undergo MRI or lumbar puncture, recently in other trials, or with conditions that interfere with the study.

What is being tested?

The trial tests MELPIDA's safety and tolerability through intrathecal injection aimed at delivering functional human AP4M1 cDNA to neurons affected by SPG50. It will monitor adverse events related to treatment and assess any improvements in disease symptoms.

What are the potential side effects?

Potential side effects include reactions specific to gene therapy such as immune responses against the vector or transgene product, issues from intrathecal administration like headache or back pain, and general risks associated with sedation required for procedures.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My SPG50 disease diagnosis was confirmed through genetic testing showing specific mutations in the AP4M1 gene.

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I have symptoms or a diagnosis of SPG50 with neurological issues.

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I can stand for more than 5 seconds.

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My ankle stiffness is mild or moderate.

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I am between 1 and 10 years old.

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I can walk 5 steps on my own or with a walker.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a condition that makes spinal taps unsafe for me.

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I am allergic or cannot take MELPIDA due to its ingredients.

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I cannot undergo certain procedures required in this study.

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My blood tests show significant abnormalities before gene therapy.

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I do not have an active infection when starting treatment.

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I have a health condition that prevents me from having a lumbar puncture or using anesthetics.

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I am allergic or cannot take certain immune suppression medications.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 60 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of unanticipated treatment-related toxicities, Grade 3 or higher in participants with SPG50

Secondary study objectives

Stability or improvement in spasticity in participants with SPG50 as measured by the Modified Ashworth scale (MAS)

Stability or improvement in spasticity in participants with SPG50 as measured by the Tardieu scale

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment ArmExperimental Treatment1 Intervention

MELPIDA, a gene therapy product

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Spastic Paraplegia, such as the one studied in the MELPIDA trial, involve gene therapy techniques that deliver functional copies of defective genes directly to neuronal cells. This approach aims to restore normal gene function and counteract neuronal loss, which is crucial for maintaining motor function and reducing spasticity. By targeting the underlying genetic cause, these treatments offer a potential for long-term improvement in symptoms and quality of life for patients with Spastic Paraplegia. This matters significantly for patients as it addresses the root cause of the disease rather than just managing symptoms, potentially leading to more effective and lasting therapeutic outcomes.

Astrocyte-selective AAV-ADAMTS4 gene therapy combined with hindlimb rehabilitation promotes functional recovery after spinal cord injury.Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use.Effects of combining methylprednisolone with rolipram on functional recovery in adult rats following spinal cord injury.