Targeted Therapy for Rare Neurological Diseases

Treating Rare Neurological Diseases

Treating Rare Neurological Diseases

Combating Adrenoleukodystrophy with Combinatorial AAV-based Gene Therapy:
A Promising Approach for Restoring Myelin Function.
Adrenoleukodystrophy (ALD/AMN) is a devastating genetic disorder characterized by the progressive destruction of myelin, the protective sheath surrounding nerve fibers. This degeneration leads to neurological impairments, ranging from behavioral problems to muscle weakness and ultimately, death. While current treatment options provide limited relief of symptoms, they fail to address the underlying cause of the disease.
A promising new approach to treating ALD/AMN involves the use of combinatorial AAV-based gene therapy. This strategy combines the delivery of multiple therapeutic genes using adeno-associated viruses (AAV), a family of non-pathogenic viruses that can efficiently deliver genes to specific cells.
One of the key therapeutic genes targeted by this approach is the ABCD1 gene, which encodes an ATP-binding cassette transporter protein responsible for transporting fatty acids across the mitochondrial membrane. Mutations in the ABCD1 gene lead to the accumulation of harmful fatty acids in the brain, contributing to myelin damage.
AAV vectors can be engineered to carry and deliver functional copies of the ABCD1 gene to affected cells, potentially restoring the normal function of myelin-producing cells (oligodendrocytes) and halting the progression of ALD/AMN.
In addition to gene therapy, vectorized antibodies, also known as nanobodies, are being explored as a potential therapeutic strategy for ALD/AMN. Nanobodies are small, highly specific fragments of antibodies derived from camelids. They can be engineered to bind to specific proteins involved in myelin damage and prevent them from exerting their harmful effects.
The combination of AAV-based gene therapy and vectorized antibodies offers a promising approach to treating ALD/AMN by addressing both the genetic defect and the underlying mechanisms of myelin destruction. This synergistic strategy holds the potential to restore myelin function, improve neurological function, and ultimately, halt the progression of this devastating disease.