Lentiviral Gene Therapy for X-ALD

2018-11-07 17:13:11 | BioPortfolio


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.


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 Design


X-linked Adrenoleukodystrophy


Intracerebral LV gene therapy


Shenzhen Geno-immune Medical Institute




Shenzhen Geno-Immune Medical Institute

Results (where available)

View Results


Published on BioPortfolio: 2018-11-07T17:13:11-0500

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A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy

In this pilot study, the investigators will assess the safety of two high-dose regimens of oral vitamin D supplementation and measure the effects of vitamin D supplementation on markers of...

Study of Glyceryl Trierucate and Glyceryl Trioleate (Lorenzo's Oil) Therapy in Male Children With Adrenoleukodystrophy

OBJECTIVES: I. Evaluate the clinical efficacy of combination glyceryl trierucate and glyceryl trioleate (Lorenzo's Oil) therapy in boys with X-linked adrenoleukodystrophy. II. Compare t...

A Clinical Study to Evaluate the Efficacy and Safety of MIN-102 (IMP) in Male AMN Patients.

This is a Phase II/III, randomized, double-blind, placebo-controlled, multicenter, two parallel-group study in male patients with the AMN phenotype of X-linked adrenoleukodystrophy (X-ALD)...

Autologous Hematopoietic Stem Cell Gene Therapy for Metachromatic Leukodystrophy and Adrenoleukodystrophy

Evaluating the safety and efficacy of Lentiviral Hematopoietic Stem Cell Gene Therapy for advanced stage of Metachromatic Leukodystrophy and adrenoleukodystrophy.

Clinical Study and Gene Mutation Analysis of Adrenoleukodystrophy in Taiwanese Children

Study the clinical manifestations and gene mutation of Taiwanese ALD patients

PubMed Articles [19170 Associated PubMed Articles listed on BioPortfolio]


To describe patients with different phenotypes of X-linked adrenoleukodystrophy: pre-symptomatic, cerebral demyelinating inflammatory adrenoleukodystrophy, adrenomyeloneuropathy and adrenal insufficie...

A Distinct Clinical Phenotype in Two Siblings with X-linked Adrenoleukodystrophy.

X-linked adrenoleukodystrophy(X-ALD) is a rare X-linked recessive metabolic disorder. The mutations in the ATP Binding Cassette Subfamily D Member 1 (ABCD1) gene account for the underlying molecular m...

Genetic analysis of a pedigree affected with X-linked adrenoleukodystrophy.

To explore the genetic basis for a pedigree affected with X-linked adrenoleukodystrophy presenting as spastic paraplegia of the lower limbs.

Novel ABCD1 gene mutations in Iranian pedigrees with X-linked adrenoleukodystrophy.

Background X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder, is caused by mutations in the ABCD1 gene located on Xq28. X-ALD is characterized by a spectrum of different mani...

Generalized skin hyperpigmentation as the only manifestation of X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is a progressive, genetic disorder caused by mutations in the ABCD1 gene that causes the accumulation of very long-chain fatty acids (VLCFA) in all tissues of the...

Medical and Biotech [MESH] Definitions

An X-linked recessive disorder characterized by the accumulation of saturated very long chain fatty acids in the LYSOSOMES of ADRENAL CORTEX and the white matter of CENTRAL NERVOUS SYSTEM. This disease occurs almost exclusively in the males. Clinical features include the childhood onset of ATAXIA; NEUROBEHAVIORAL MANIFESTATIONS; HYPERPIGMENTATION; ADRENAL INSUFFICIENCY; SEIZURES; MUSCLE SPASTICITY; and DEMENTIA. The slowly progressive adult form is called adrenomyeloneuropathy. The defective gene ABCD1 is located at Xq28, and encodes the adrenoleukodystrophy protein (ATP-BINDING CASSETTE TRANSPORTERS).

An ATP-Binding Cassette Transporter that functions in the import of long chain (13-21 carbons) and very long chain fatty acids (> 22 carbons), or their acyl-CoA-derivatives, into PEROXISOMES. Mutations in the ABCD1 gene are associated with the X-linked form of ADRENOLEUKODYSTROPHY.

A heterogeneous group of inherited metabolic disorders marked by absent or dysfunctional PEROXISOMES. Peroxisomal enzymatic abnormalities may be single or multiple. Biosynthetic peroxisomal pathways are compromised, including the ability to synthesize ether lipids and to oxidize long-chain fatty acid precursors. Diseases in this category include ZELLWEGER SYNDROME; INFANTILE REFSUM DISEASE; rhizomelic chondrodysplasia (CHONDRODYSPLASIA PUNCTATA, RHIZOMELIC); hyperpipecolic acidemia; neonatal adrenoleukodystrophy; and ADRENOLEUKODYSTROPHY (X-linked). Neurologic dysfunction is a prominent feature of most peroxisomal disorders.

The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia.

ATP-dependent DNA helicase that contains two N-terminal ZINC FINGERS and C-terminal ATP-binding and helicase domains. It functions in the regulation of gene transcription and CHROMATIN REMODELING. ATRX undergoes cell-cycle dependent phosphorylation, which causes it to translocate from the NUCLEAR MATRIX to CHROMATIN; thus, it may change its role from gene regulation during INTERPHASE to ensuring proper chromosome segregation at MITOSIS. Mutations in the ATRX gene are associated with cases of X-LINKED MENTAL RETARDATION co-morbid with ALPHA-THALASSEMIA (ATRX syndrome).

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