The human brain is a complex and intricate network of cells and molecules that control every aspect of our behaviour and cognitive function. The delicate balance of the brain activity is subject to disruption because of aging or genetic causes. The paper of S. S. Braga reports on the recent studies on the potential role of cyclodextrins in the treatment of brain disorders such as Niemann-Pick disease (NPD), Alzheimer’s disease, and Parkinson’s disease . These diseases share as a common background the abnormal accumulation of cholesterol and other lipids in brain cells or certain areas of the brain tissue.
The unique cholesterol-sequestering ability of cyclodextrins has attracted attention to their potential medicinal use. In particular, 2‑hydroxypropyl-β-cyclodextrin (HPβCD), having high biocompatibility and toxicological safety, has been intensively investigated for the treatment of NPD, a rare and life-threatening genetic condition involving cholesterol metabolism. Early positive results in animal models such as mice and cats prompted the approval of HPβCD as an orphan drug, and allowed conducting several clinical trials on babies and children suffering from NPD. Several patients had improved life quality and slowed disease progression. Nevertheless, the fact that NPD is a rare disease has limited the number of patients enrolled in each trials and hampered obtaining statistically-relevant outcomes. Research is ongoing with the ultimate goal of approval of the clinical label of HPβCD as a medicine for NPD.
In addition to Niemann-Pick disease, HPβCD has shown promise as a treatment for Alzheimer’s and Parkinson’s disease. Besides lipid dysfunction, these disorders are characterized by abnormal protein aggregates in the brain. The studies compiled in the present review show that HPβCD can bind directly to the aggregates when administered in the brain tissue, as well as regulate the expression of proteins involved in autophagy, the process of removal of cellular waste – lipids and other proteins – thus restoring normal functioning of brain cells. A new large-scale clinical trial that is set to evaluate the safety and efficacy of HPβCD in the treatment of Alzheimer’s disease is ongoing, and it will set the compass towards the future medicinal use of this cyclodextrin.
 Susana Santos Braga, Molecular Mind Games: The Medicinal Action of Cyclodextrins in Neurodegenerative Diseases. Biomolecules 2023, 13(4), 666; https://doi.org/10.3390/biom13040666