Poster: Adrabetadex alone or in combination with arimoclomol and levacetylleucine promotes oligodendrocyte proliferation, synaptic network growth, and myelination in an in vitro mouse model of Niemann-Pick disease type C

Citation: Burchard J, et al. Adrabetadex alone or in combination with arimoclomol and levacetylleucine promotes oligodendrocyte proliferation, synaptic network growth, and myelination in an in vitro mouse model of Niemann-Pick disease type C. Poster presented at: National Niemann-Pick Disease Foundation (NNPDF) Family and Medical Conference; July 2026.

Plain Language Summary: Results of laboratory studies examining whether adrabetadex (formerly VTS-270, cyclodextrin) and two other approved Niemann-Pick Disease Type C (NPC) treatments, arimoclomol and levacetylleucine (NALL), interact with each other, or produce greater benefit than any single treatment alone.

What is this study about?

Families and physicians now have more treatment options for NPC than ever before. An important question is whether these treatments can be safely used together and whether combining them may provide greater benefit than using any one treatment alone. Until recently, there were very few treatment options for NPC. Now, for the first time, three treatments with distinct mechanisms of action are available or in development for the disease's neurological symptoms: adrabetadex (investigational, not yet U.S. Food and Drug Administration [FDA] approved), arimoclomol (FDA approved as Miplyffa), and levacetylleucine (also called NALL, FDA approved as Aqneursa). 

This study addressed both questions in a laboratory setting. First, it tested whether adrabetadex physically binds to arimoclomol or NALL in a way that could interfere with how they work. Next the researchers measured what each treatment does to key features of NPC-affected brain cells when used alone, and then what happens when they are combined.

What are the three treatments, and how do they work differently?

Each of the three treatments targets NPC through distinct pathways:

• Adrabetadex: Investigational treatment that helps restore the normal movement of cholesterol inside cells, addressing the underlying biological problem that causes NPC.
• Arimoclomol: Helps cells respond to stress, although the exact mechanism is unknown. It is FDA-approved for use in combination with miglustat in patients with NPC aged 2 years and older.
• Levacetylleucine / NALL: May improve how nerve cells produce energy. It is FDA-approved for patients with NPC who weigh at least 15 kg/33 lbs.  

What did the study do?

The researchers used two approaches: a computational (computer-based) analysis to check for potential drug interactions, and a laboratory experiment using brain cells to measure biological effects.

For the drug interaction computational analysis, they used molecular modeling techniques, simulating at the atomic level whether arimoclomol or NALL could physically fit into the cavity inside the adrabetadex molecule and compete with cholesterol for that space. They also directly measured the binding affinity using a laboratory technique called isothermal titration calorimetry (ITC), which detects heat changes when molecules interact.

For the cell culture experiments, the researchers grew brain cells from NPC mice, specifically a mixture of neurons and glial cells including oligodendrocytes, which are the cells responsible for producing the myelin sheath that insulates and protects nerve fibers. These cultures were treated with each treatment individually at a range of doses, and then with combinations of adrabetadex together with arimoclomol or NALL. After treatment, the researchers measured three outcomes:

• Synaptic network growth: how well neurons extended their projections and formed connections with each other.
• Oligodendrocyte differentiation: how many oligodendrocytes matured into cells capable of producing myelin.
• Myelination: how much of the nerve fiber network was actually coated with the protective myelin sheath.

What the study found:

The results show a potential for meaningful additive benefit from combining the treatments, and no problematic drug interactions.

• Adrabetadex was the most potent single agent: When used alone, adrabetadex was the most potent of the three treatments across all of the measured cellular endpoints. It produced significant effects at much lower concentrations than arimoclomol or NALL, consistent with its direct action on the root cause of NPC.
• Adrabetadex + arimoclomol: additive and potentially greater benefit: When adrabetadex was combined with arimoclomol, the combination produced additive improvements in oligodendrocyte differentiation and myelination and showed evidence of a greater-than-expected benefit in synaptic network growth. Notably, some dose combinations that were individually inactive as monotherapy produced significant improvements in myelination when used together.
• Adrabetadex + NALL: additive benefits across all measures: When adrabetadex was combined with NALL, the combination produced additive improvements across all three endpoints at concentrations substantially lower than either treatment would require alone.
• No drug-drug interaction detected: The computer simulations showed that adrabetadex is unlikely to bind with arimoclomol or NALL instead of its intended target (cholesterol), and the treatments are not expected to interfere with each other's function.

Why does this matter?

The NPC treatment landscape has changed significantly in recent years. For the first time, patients have access to multiple treatments that target different aspects of the disease, and this study provides early scientific evidence that these treatments can be used together safely and effectively.

The finding that there is no meaningful interaction between adrabetadex and the other two treatments is reassuring: they appear to work independently without interfering with each other. And the combination data suggest that using them together is safe at the cellular level, and may provide greater benefit than any single therapy alone, potentially at lower individual doses.

This is particularly important for patients with I-NPC, who have the fewest approved treatment options and the most rapid disease progression. The ability to layer complementary therapies on top of a foundational treatment like adrabetadex could offer a more comprehensive approach to slowing the multiple ways NPC damages the brain.

What this means for patients:

This laboratory study provides important early evidence that adrabetadex, arimoclomol, and NALL can work together without interfering with each other, and that combining them may produce greater benefits for brain cell health than using any one treatment alone. The results support the concept of adrabetadex as a foundational therapy, one that directly targets the root cause of NPC, while arimoclomol and NALL address complementary aspects of the downstream damage.

For families and clinicians, these findings offer scientific reassurance that using these treatments together is a biologically reasonable approach, and they lay an important mechanistic foundation for the real-world combination therapy patterns already emerging in clinical practice.

What this means for families:

For families living with NPC, having more than one treatment option creates new opportunities, but it also raises an important question: can these therapies be used together safely, and could they provide greater benefit than using any one treatment alone?

This study provides encouraging early laboratory evidence that adrabetadex, arimoclomol, and levacetylleucine do not interfere with one another and may work together by targeting different aspects of the disease. Rather than competing, the treatments appeared to complement each other, producing greater improvements in measures of brain cell health than individual treatments alone.

While these findings come from laboratory studies and need to be confirmed in patients, they provide important scientific support for an emerging approach to I-NPC treatment in which adrabetadex serves as a foundational therapy and additional treatments are layered on to address different aspects of the disease. Together, these findings give families and clinicians greater confidence that combination therapy is a biologically sound strategy worthy of continued study.