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X-ALD Patients Hope to See Results With Cell-Based Gene Therapy

Mar 31, 2020 10:06:00 AM / by Stacy Matthews Branch, DVM, PhD

Brain charging and mental rest. Plug and cable leads to plastiline meanders on blue background top view space for text_AdobeStock_299019799-1As Phase 3 clinical trials begin for Lenti-D as a treatment for patients with X-ALD, the drug also shows promise for treating a range of neurodegenerative diseases.

X‐linked adrenoleukodystrophy (X‐ALD) is a peroxisomal disorder resulting from a mutation in the human ATP-binding cassette, sub-family D, member 1 gene (ABCD1). The ABCD1 gene codes for the adrenoleukodystrophy protein (ALDP) needed for very-long-chain fatty acids (VLCFAs) to enter peroxisomes for degradation. When this process is disrupted, the VLCFAs accumulate in various tissues of the body, including the brain. VLCFA accumulation and demyelination of brain white matter lead to the severe neurological symptoms seen with X-ALD.

Many may recall the movie, Lorenzo’s Oil, based on the true story of a boy with X-ALD. Lorenzo’s oil is actually a mixture of monounsaturated long-chain fatty acids and is still studied as a potential treatment at the asymptomatic stage to prevent the development of cerebral ALD. Approaches available 30 years ago to treat X-ALD focused on the use of hematopoietic stem cells (HSCs) derived from the bone marrow of healthy volunteers. Beneficial effects were achieved, but only if treatment was performed at the early stages of the disease.

In 2016, a Phase 2/3 study using the Lenti-D approach was conducted. CD34+ HSCs were obtained from the bone marrow of patients with X-ALD and transduced with Lenti-D lentiviral vector encoding, a nonmutated, functional form of ABCD1 cDNA. The transduced cells were infused back into patients and proliferated. With this approach, some of the cells can reach the brain and differentiate into microglial cells, specialized macrophages of the central nervous system. The expressed ABCD1 in the cells restores ALDP function to halt or delay disease progression. Patients in this trial were clinically free of significant functional neurological symptoms up to 24 months after the initiation of treatment.

The company Bluebird Bio is recruiting for a Phase 3 clinical trial to determine the clinical efficacy of Lenti-D as a treatment for X-ALD. Twenty young male patients with X-ALD will be treated in the international, multisite trial. The Lenti-D approach has the potential to provide clinical benefit for not only the treatment of X-ALD, but for other serious neurodegenerative diseases such as Alzheimer’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, and more.

HemaCare recently launched a new product, GMP bone marrow aspirate, in support of medical research and eventual commercialization of cell and gene therapy treatments. Learn more about GMP-compliant bone marrow aspirate.


Resource: Cell-based Gene Therapy Represents 'Hope' for X-ALD Patients, Review Study Suggests. (2019). Adrenoleukodystrophy News. Retrieved 2 December 2019, from

Topics: Gene Therapy, Bone Marrow, Cell Therapy, CNS/Neurodegeneration

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