Lentiviral Vector Development for Cerebral Adrenoleukodystrophy
Gene therapy using lentiviral vectors (LVs) has emerged as a promising treatment for patients with cerebral adrenoleukodystrophy (cALD), making LVs an attractive potential alternative to allogeneic transplant for those with cALD for multiple reasons. Equipped with world-leading technology platforms and professional scientific staff, Creative Biolabs is dedicated to offering high-quality service of LV development for cALD to meet our clients' development goal in a time-saving manner.
Introduction of cALD
cALD is characterized by demyelination and neurodegeneration. Disease progression, which leads to loss of neurologic function and death, can be halted only with allogeneic hematopoietic stem-cell transplantation. Adrenoleukodystrophy, an X-linked genetic disease, is caused by a defect in the gene ATP-binding cassette subfamily D member 1 (ABCD1). ABCD1 encodes the peroxisomal ABC half-transporter ALD protein and mutations in this gene resulting in the abnormal breakdown of very-long-chain fatty acids. CALD may develop in approximately 35% of affected boys younger than 12 years old. Learning and behavioral manifestations are often observed when affected patients are between 3-15 years-old, and rapidly progressive loss of neurologic function follows.
Figure 1. Example of Loes scores, but not DTI values, predicting clinical outcome in our patients with ALD. (McKinney, 2013)
Treatment of cALD
Allogeneic transplantation is the only effective therapy for cALD. If they are not treated with hematopoietic stem-cell transplantation, most patients with this disease die in 10 years after diagnosis. It is more likely to be effective if it is performed at an early stage of neurodegeneration. The long-term benefits of hematopoietic stem-cell transplantation in cALD are thought to be mediated by donor-derived replacement of myeloid-derived cells. The most successful outcomes to date have been achieved with the use of cells from HLA-identical, unaffected related donors. Although overall survival is good, treatment failure is usually due to transplantation-related complications or rapid disease progression during the engraftment of donor cells.
Gene therapy is another strategy for the treatment of cALD. Gene therapy can eliminate the risk for graft-versus-host disease, the need for related immune-suppressing medications and the need to find an allogeneic stem cell donor. Pilot studies have shown that patients after gene therapy with the lentiviral drug had a functional expression of ALD protein and disease stabilization. Thus, gene therapy with LVs is an alternative to allogeneic hematopoietic stem-cell transplantation.
LV Development for cALD at Creative Biolabs
Since LVs can insert into the host genomic DNA and are replicated with cell division, they are categorized as integrating vectors. These features are important in the treatment of cALD, as stable and long-term protein expression is essential to the success of treatment. Creative Biolabs is fully competent and dedicated to LV development for gene therapy in patients with cALD. Our scientists are pleased to share our cutting-edge technology and extensive expertise in LV development for cALD to facilitate our clients' research and project development.
Key Advantages of Our Service
- Large-scale production of LVs with features, such as high transduction rates, infection of non-dividing cells and not to expected to elicit immunogenic responses.
- Keeping stable and long-term protein expression
- Powered by a proven, first-in-class technology
- Fast turnover time
Enriched experience, profound expertise and state-of-the-art instruments, all of these can ensure that Creative Biolabs offers high-quality services for LV development for cALD. If you are interested in the development of LV for the treatment of cALD, please contact us for more information and a detailed quote.
Reference
- McKinney, A.M.; et al. (2013). Childhood cerebral X-linked adrenoleukodystrophy: diffusion tensor imaging measurements for prediction of clinical outcome after hematopoietic stem cell transplantation. AJNR Am J Neuroradiol. 34(3):641-9.
