Posted by Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND), is a rare and terminal neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. Starting from gradual muscle wasting, motor neuron loss continues until the abilities to eat, speak, move, or, lastly, breathe are lost. There is no cure for ALS, the progression of the disease can be slowed down.
One of the protein degradation genes that can cause ALS when mutated is SOD1. SOD1 protein forms intracellular aggregations that inhibit protein degradation. It has been shown that blocking amyloid-beta (Aß) production improves outcome measures in SOD1G93A mice. HP-β-CD has previously been shown to deplete intraneuronal unesterified cholesterol, resulting in effective reduction of Aß production and amelioration of disease progression in mouse models of AD and Niemann Pick Type C (NPC) disease. In this work it was tested whether HP-β-CD could also improve phenotypic progression in SOD1G93A mice.
The findings of a recent study clearly demonstrate that HP-β-CD treatment does not positively modify disease progression in SOD1G93A mice, at least at the dose (4000 mg/kg) and subcutaneous administration route, a treatment regime that has previously been shown to be effective at preventing intraneuronal accumulation of unesterified cholesterol in the CNS of NPC mouse models [1].
[1] Linda Greensmith & J. Barney Bryson (2023) The cholesterol depleting agent, (2-Hydroxypropyl)-ß-cyclodextrin, does not affect disease progression in SOD1G93A mice, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 24:7-8, 756-762, DOI: 10.1080/21678421.2023.2239867