Posted by HP-beta-cyclodextrin (HPbCD) is currently in clinical trials against Niemann-Pick Disease Type C (NPC) and Alzheimer’s Disease (AD) and these trials have confirmed its risk of causing cholesterol-related hearing loss, which can be permanent.
At the AAIC 2022, ASDERA is presenting results from its own and and others’ published studies [1], which suggest that HPbCD’s mechanism-of-action in many diseases (and, at least in part, even in NPC [2]) may be to “deplete” non-essential serum phospholipids rather than cholesterol. Hence HP-alpha-cyclodextrin (HPaCD) emerges as a safer (too small to fit cholesterol) and, often more effective intervention, as suggested, for instance, in models of several LSDs [3].
In the current trials, HPbCD is administered by overnight intravenous infusion (every other week), which is both inconvenient and inconsistent with having constant serum levels. ASDERA’s has developed a compound (ASD-005) [4] that allows HPaCD to be reliably absorbed from the intestine (rather than partially when taken with milk) and, thus, to be administered daily per os.
[1] Wittkowski (2022) A novel oral formulation (CoM pat. pend.) of HP-alpha-cyclodextrin as a safe (not ototoxic) and convenient (oral) drug against Alzheimer’s disease. San Diego: Alzheimer’s Association. https://app.box.com/s/2fbnmhq9rorfd99faz7x3ubrk1hgj7yq
[2] Davidson (2016). Efficacy and ototoxicity of different cyclodextrins in Niemann-Pick C disease. Ann Clin Transl Neurol 3: 366-80
[3] McKew (2021) Cyclodextrin for the treatment of lysosomal storage diseases. US 11020422 B2
[4] Wittkowski (2019) Use of Cyclodextrins in Diseases and Disorders Involving Phospholipid Dysregulation. WO 2019/067269 A2