Lentiviral Gene Therapy for X-ALD

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Brief Title

Lentiviral Gene Therapy for X-ALD

Official Title

Lentiviral Gene Therapy for X-linked Adrenoleukodystrophy (X-ALD)

Brief Summary

      This is a Phase I/II clinical trial of gene therapy for treating X-linked
      adrenoleukodystrophy using a high-safety, high-efficiency, self-inactivating lentiviral
      vector TYF-ABCD1 to functionally correct the defective gene. The objectives are to evaluate
      the safety and efficacy of the gene transfer clinical protocol.

Detailed Description

      X-linked adrenoleukodystrophy (X-ALD) is a devastating neurological disorder caused by
      mutations in the ABCD1 gene that encodes a peroxisomal ATP-binding cassette transporter
      (ABCD1). ABCD1 is responsible for transport of CoA-activated very long-chain fatty acids
      (VLCFA) into the peroxisome for degradation. X-ALD is clinically characterized by two main
      phenotypes: adrenomyeloneuropathy (AMN) and the inflammatory cerebral ALD. This diease
      presents most commonly in males. Approximately 50% of heterozygote females show some symptoms
      later in life. Approximately two-thirds of ALD patients will present with the childhood
      cerebral form of the disease, which is the most severe form. The disease is characterized by
      normal development in early childhood, followed by rapid degeneration to a vegetative state.
      ALD patients are normally treated with haematopoietic stem cell transplantation (HSCT) from a
      matched healthy donor. However, HSCT must be performed at a very early stage of the disease,
      which limits the therapeutic opportunies for juvenile or adult forms of ALD. This trial aims
      to treat ALD using a safety and efficiency improved self-inactivating lentiviral vector
      carrying a functional ABCD1 gene to correct the genetic defect. By Intracerebral injection to
      delivery the lentiviral vector with a normal ALD gene to correct the pathologies associated
      with this genetic defect.

      The primary objectives are to evaluate the safety of the advanced self-inactivating
      lentiviral vector TYF-ABCD1, the in-vivo gene transfer clinical protocol and the efficacy of
      degradative metabolite in patients at the time of treatment, assessment of vector integration
      sites, and finally the long-term correction of patients' disease beheviors.

Study Type


Primary Outcome

Safety evaluation of intracerebral injection of lentiviral TYF-ABCD1, determined by number of participants with treatment-related adverse events (AEs), according to scheduled assessments, vital signs, & physical examinations as assessed by CTCAE v4.0.


X-linked Adrenoleukodystrophy


Intracerebral LV gene therapy

Study Arms / Comparison Groups

 Lentivirus-mediated delivery of ABCD1 to the CNS.
Description:  Intracerebral injection with lentiviral TYF-ABCD1 vector carrying the functional gene


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

October 30, 2018

Completion Date

October 30, 2020

Primary Completion Date

October 30, 2018

Eligibility Criteria

        Inclusion Criteria:

          1. X-ALD patients ≥0 years of age

          2. ALD diagnosis of the brain: evaluation of the VLCFA value in plasma

          3. Central imaging of the MRI to examine the damage on the CNS.

          4. Neurological function score (NFS) ≥ 1

          5. Parent / guardian / patient signing informed consent

          6. Patients and their families have a strong willingness to participate in clinical
             trials, and are willing to bear all the consequences caused by the failure of the
             trial, and sign an informed consent form

        Exclusion Criteria:

          1. HIV positive patients

          2. Stablized condition after statins, Lorenzoas oil, or diet to reduce VLCFA levels

          3. Patients who are experiencing severe viral, bacterial or fungal infections, malignant
             tumors, heart abnormalities, liver dysfunction, or renal insufficiency

          4. Cannot perform an MRI

          5. Infection or dermatosis at pre-injection site




N/A - N/A

Accepts Healthy Volunteers



, 86-0755-86725195, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Shenzhen Geno-Immune Medical Institute

Study Sponsor

, , 

Verification Date

September 2019