Adrenoleukodystrophy (ALD)
https://www.mdpi.com/1422-0067/26/23/11645
X-linked adrenoleukodystrophy (X‑ALD) is a genetic condition caused by faults in the ABCD1 gene. Importantly, the type of mutation does not predict which form of the disease a person will develop. Current treatments are limited — stem cell transplantation only helps early cerebral ALD, and existing gene therapy approaches carry risks and do not treat adrenomyeloneuropathy (AMN). The article discusses AAV-based gene therapy as a new and promising option for treating the neurological symptoms of X‑ALD and the different aspects to consider when designing the therapy. AAV (adeno-associated virus) is considered safer because it does not insert its DNA into the patient’s genome. There are some challenges due to the condition affecting both the central and peripheral nervous system, therefore it is important to select a good AAV type. Certain AAV types, such as AAV9, naturally target the brain and spinal cord, making them suitable for delivering a healthy copy of the ABCD1 gene. Successful therapy depends on choosing the right viral shell (capsid), designing the correct genetic package, avoiding toxicity while making sure there is therapeutic effect, and selecting the best delivery method — with intrathecal injection (injected into the spinal cord) being the most direct route to the central nervous system. The article also explains how VLCFA buildup harms cells and highlights microglia and astrocytes as key targets for therapy. Overall, it supports AAV-based delivery of ABCD1 as a strong candidate for the potential treatment of neurological forms of X‑ALD.