4 Participants Needed

Gene Therapy for Spastic Paraplegia

DK
SM
SC
Overseen BySydney Cooper, MSc
Age: < 18
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Elpida Therapeutics SPC
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that if you have a condition requiring chronic drug treatment that poses risks for gene transfer, you may be excluded. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment MELPIDA, AAV9/AP4M1, hAP4M1opt for spastic paraplegia?

Preclinical studies show that the AAV9/AP4M1 gene therapy can partly fix the problems in cells and mice with spastic paraplegia 50, and it is safe in animals like rodents and monkeys. This suggests it might help treat this condition in humans.12345

Is the gene therapy AAV9/AP4M1 safe for humans?

Preclinical studies on AAV9/AP4M1 gene therapy for spastic paraplegia 50 showed an acceptable safety profile in animals like mice, rats, and monkeys, with minimal-to-mild side effects observed. This suggests it may be safe for humans, but more research is needed to confirm this.23467

How is the treatment MELPIDA different from other treatments for spastic paraplegia?

MELPIDA is a gene therapy that uses a virus to deliver a healthy version of the AP4M1 gene directly into the spinal fluid, aiming to address the root cause of spastic paraplegia 50, unlike current treatments that only manage symptoms.248910

Research Team

Susan Iannaccone, M.D.: Pediatrics ...

Susan Iannaccone, MD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

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.

Inclusion Criteria

I can stand for more than 5 seconds.
My ankle stiffness is mild or moderate.
My SPG50 disease diagnosis was confirmed through genetic testing showing specific mutations in the AP4M1 gene.
See 5 more

Exclusion Criteria

I have a condition that makes spinal taps unsafe for me.
I am allergic or cannot take MELPIDA due to its ingredients.
Enrollment and participation in another interventional clinical trial
See 11 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of MELPIDA via intrathecal injection to deliver a fully functional human AP4M1 cDNA copy

1 day
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of spasticity and adverse events

60 months

Treatment Details

Interventions

  • MELPIDA
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment ArmExperimental Treatment1 Intervention
MELPIDA, a gene therapy product

MELPIDA is already approved in United States, Canada for the following indications:

🇺🇸
Approved in United States as MELPIDA for:
  • Spastic Paraplegia Type 50 (SPG50)
🇨🇦
Approved in Canada as MELPIDA for:
  • Spastic Paraplegia Type 50 (SPG50)

Find a Clinic Near You

Who Is Running the Clinical Trial?

Elpida Therapeutics SPC

Lead Sponsor

Trials
4
Recruited
60+

University of Texas Southwestern Medical Center

Collaborator

Trials
1,102
Recruited
1,077,000+

Cure SPG50

Collaborator

Trials
1
Recruited
4+

Findings from Research

The study successfully constructed both wild-type and mutant SPAST vectors to investigate hereditary spastic paraplegia, using COS7 cells for transfection and analysis.
Results showed that while wild-type spastin localized in the plasma membrane, the mutant spastin maintained the same localization and neither form co-localized with microtubules or mitochondria, suggesting a specific role for spastin that does not involve these cellular structures.
[Construction of wild-type and mutant SPAST vectors for the study of molecular mechanism of hereditary spastic paraplegia].Yan, YP., Pu, JL., Zhang, BR., et al.[2019]
AAV-mediated AP4M1 gene replacement therapy shows promise in preclinical studies for treating spastic paraplegia 50 (SPG50), demonstrating the ability to partially rescue functional defects in cellular and mouse models.
The therapy exhibited acceptable safety profiles in both rodent and monkey models, paving the way for potential clinical trials and representing a significant advancement in the search for effective treatments for SPG50.
Paving a way to treat spastic paraplegia 50.Brent, JR., Deng, HX.[2023]
AAVrh10, a specific adeno-associated virus serotype, was found to be the most effective for gene delivery in a chronic spinal cord injury mouse model, showing the highest photon count in bioluminescence imaging and greater expression of the reporter protein Venus.
This serotype demonstrated favorable targeting of key cell types in the spinal cord, including neurons, astrocytes, and oligodendrocytes, suggesting its potential as a safe and effective tool for gene therapy in chronic spinal cord injuries.
The adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury.Hoshino, Y., Nishide, K., Nagoshi, N., et al.[2021]

References

[Construction of wild-type and mutant SPAST vectors for the study of molecular mechanism of hereditary spastic paraplegia]. [2019]
Paving a way to treat spastic paraplegia 50. [2023]
The adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury. [2021]
Intrathecal AAV9/AP4M1 gene therapy for hereditary spastic paraplegia 50 shows safety and efficacy in preclinical studies. [2023]
Comparison of adeno-associated viral vector serotypes for spinal cord and motor neuron gene delivery. [2011]
Clinical Trial Designs and Measures in Hereditary Spastic Paraplegias. [2020]
Dalfampridine in hereditary spastic paraplegia: a prospective, open study. [2018]
AAV9-mediated FIG4 delivery prolongs life span in Charcot-Marie-Tooth disease type 4J mouse model. [2023]
Systematic Analysis of Brain MRI Findings in Adaptor Protein Complex 4-Associated Hereditary Spastic Paraplegia. [2022]
Putative founder effect of Arg338* AP4M1 (SPG50) variant causing severe intellectual disability, epilepsy and spastic paraplegia: Report of three families. [2023]