Alexander Gold, MD, Discusses the Impact of Adrabetumlimab on Infantile-Onset Niemann-Pick Disease Type C: Insights from NeurologyLive

Hope Emerges for Young Patients: Novel Therapy Demonstrates Survival Benefit in Rare Neurological Disorder

Charlotte,North Carolina – In a meaningful development for the treatment of debilitating rare diseases,new findings presented at the 2025 Child Neurology Society (CNS) Annual Meeting indicate a potential breakthrough for children diagnosed with infantile-onset Niemann-Pick disease type C (NPC). Researchers shared promising survival data and biomarker analyses related to adrabetadex, an investigational treatment developed by Mandos Health by Beren Therapeutics P.B.C.

Infantile-onset NPC presents a especially aggressive form of the neurodegenerative disorder, affecting young children before the age of six. This condition impairs the body’s ability to effectively process cholesterol, leading to its toxic build-up within the brain and other vital organs. Consequently, patients typically experience rapid neurological decline and a tragically shortened lifespan.

Understanding Adrabetadex and its Mechanism

Adrabetadex, a unique formulation of 2-hydroxypropyl-β-cyclodextrin isomers, is designed to directly address the underlying cause of NPC. According to Alexander Gold, MD, Chief Medical Officer of Mandos Health, the therapy aims to restore proper cholesterol trafficking within cells, particularly neurons. Clinical studies have shown that treatment with adrabetadex is associated with increased levels of a specific cholesterol metabolite in cerebrospinal fluid, indicating a return toward normal cellular function.

Furthermore, the treatment appears to reduce biomarkers linked to neuronal damage and cell death, suggesting a protective effect on the brain.These biological indicators lend strong support to the potential of adrabetadex to modify the course of this devastating illness.

Key Findings from the CNS 2025 Presentation

The survival analysis, presented at the CNS meeting in October, compared outcomes for children receiving intrathecal adrabetadex with a matched control group from established natural history databases. The results reveal a statistically significant and clinically meaningful increase in survival rates among those treated with the investigational drug. this suggests that adrabetadex not only impacts the biological mechanisms of the disease but translates into tangible benefits for patients.

The investigations incorporated extensive, long-term data and utilized rigorous analytical methods for a more accurate understanding of adrabetadex’s effect on disease progression.These combined results reinforce the therapeutic promise of targeting cholesterol trafficking impairment in NPC.

Feature	Adrabetadex Treated Group	matched Control Group
Survival Rate	Statistically Significant Increase	Baseline
Cholesterol Trafficking	Restored (Increased CSF Levels)	Impaired
Neuronal Injury Biomarkers	Decreased	Elevated

Challenges and Collaborative Progress in NPC Treatment

Developing effective therapies for infantile-onset NPC has faced significant hurdles due to the disease’s rarity,the variability in how it presents in different patients,and the complexities of conducting clinical trials with small patient populations. Historically, assessing treatment efficacy was arduous due to short study durations and limitations in identifying sensitive measures of disease progression.

Though, recent years have witnessed increased collaboration between Mandos Health, academic institutions, patient advocacy groups, and regulatory bodies. These cooperative efforts have expanded access through programs like Expanded Access Programs and facilitated the collection of shared natural history data, leading to more robust analyses. Enhanced biomarker utilization has also provided objective measures to correlate biological activity with clinical outcomes.

Did You Know? Niemann-pick disease affects an estimated 1 in 100,000 to 1 in 120,000 live births, making it one of the rarest genetic disorders.

prioritizing Patient Needs and Future directions

For families navigating infantile-onset NPC, time is of the essence. The rapid progression of the disease creates an urgent need for therapies that can slow decline and improve quality of life. The positive survival data associated with adrabetadex offers a beacon of hope, perhaps providing more opportunities for developmental milestones and precious time with loved ones.

Early and accurate diagnosis remains crucial. Clinicians must be vigilant in recognizing early neurological symptoms and initiating appropriate testing. Mandos Health remains committed to supporting physicians, researchers, and families through education, access programs, and compassionate care.

Pro Tip: If you suspect a child may have symptoms of Niemann-Pick disease, consult with a neurologist specializing in rare genetic disorders for prompt evaluation and guidance.

Understanding Niemann-pick Disease Type C

Niemann-Pick disease type C is a genetic disorder characterized by the body’s inability to properly metabolize cholesterol and other lipids. This leads to their accumulation in cells, particularly in the liver, spleen, and brain. While various forms of Niemann-Pick disease exist, type C is the most common and often manifests with neurological symptoms, especially in early childhood.The condition is caused by mutations in the NPC1 or NPC2 genes, which are responsible for producing proteins involved in lipid transport.Ongoing research focuses on developing additional therapies, including gene therapy and substrate reduction strategies, to address the underlying genetic defects and improve outcomes for affected individuals. The National Niemann-Pick Disease Foundation (NNPDF) offers extensive resources and support for patients and families: https://www.nnpdf.org/.

Frequently Asked Questions About Niemann-Pick Disease and Adrabetadex

• What is Niemann-Pick disease type C? It’s a rare,inherited metabolic disorder that disrupts the body’s cholesterol processing,leading to buildup in organs and tissues.
• How does adrabetadex work in treating NPC? Adrabetadex attempts to restore proper cholesterol trafficking within cells, addressing the root cause of the disease.
• What were the key findings of the CNS 2025 presentation? The study showed a statistically significant increase in survival rates among children treated with adrabetadex compared to controls.
• What are the challenges in developing NPC treatments? The disease’s rarity, variable presentation, and small patient populations pose difficulties in conducting clinical trials.
• Where can families find more facts and support for NPC? The National Niemann-Pick Disease Foundation (NNPDF) is a valuable resource: https://www.nnpdf.org/.
• Is adrabetadex currently approved for use? No, adrabetadex is still an investigational treatment and has not yet been approved by regulatory authorities.
• What biomarkers are used to monitor the effects of adrabetadex? Levels of 24(S)-hydroxycholesterol, calbindin D, and fatty acid-binding protein 3 are monitored to assess cholesterol trafficking and neuronal injury.

What are your thoughts on the potential of adrabetadex to change the lives of children with NPC? Share your comments below, and help spread awareness about this critically important research!

What are the key mechanisms by which adrabetumlimab aims to address the underlying pathophysiology of infantile-onset NPC?

Understanding Niemann-Pick Disease Type C (NPC)

Niemann-Pick Disease Type C (NPC) is a rare, progressive genetic disorder affecting lipid metabolism. Specifically,it impacts the body’s ability to transport cholesterol and other lipids within cells,leading to their accumulation. This buildup primarily affects the liver, spleen, lungs, and brain. Infantile-onset NPC, as the name suggests, presents in early childhood and is often characterized by more severe and rapid progression.Common symptoms include:

* Hepatosplenomegaly (enlarged liver and spleen)

* Difficulty feeding and failure to thrive

* Neurological deterioration – ataxia (loss of coordination), dystonia (involuntary muscle contractions)

* progressive cognitive decline

* Vertical supranuclear gaze palsy (difficulty moving eyes vertically)

Diagnosis of NPC often involves a combination of clinical evaluation, genetic testing, and biochemical assays like oxysterol analysis. Early and accurate diagnosis is crucial for initiating appropriate management strategies.

Adrabetumlimab: A Novel Therapeutic Approach

Adrabetumlimab,developed by BridgeBio Pharma,represents a perhaps groundbreaking treatment for infantile-onset NPC. It’s a monoclonal antibody designed to block the PCSK9 protein. PCSK9 regulates the levels of the LDL receptor, which is responsible for clearing LDL cholesterol from the blood. By inhibiting PCSK9, adrabetumlimab aims to increase LDL receptor availability, enhancing cholesterol clearance and potentially reducing lipid accumulation in affected tissues. This mechanism differs substantially from traditional symptomatic treatments for NPC.

Dr.Alexander Gold’s Insights from NeurologyLive

Alexander gold, MD, a leading neurologist specializing in lysosomal storage disorders, recently shared valuable insights regarding adrabetumlimab and its impact on infantile-onset NPC through NeurologyLive. His commentary focuses on the clinical trial data and the potential for this therapy to alter the disease course.

Key Findings Discussed by Dr. Gold

Dr. Gold highlighted several key findings from the clinical trials:

1. Neurological Stabilization: Data suggests adrabetumlimab may slow neurological deterioration in some patients. This is assessed through standardized neurological assessments,including measures of ataxia and cognitive function. The stabilization, rather than reversal, of neurological decline is a significant observation.
2. Visceral Response: Improvements were observed in visceral manifestations of the disease, such as reduced liver volume and improved spleen size. This suggests the drug is effectively targeting lipid accumulation in peripheral organs.
3. Biomarker Changes: The trials demonstrated changes in key biomarkers associated with NPC,including reductions in plasma oxysterols. These biomarker changes correlate with clinical improvements, providing further evidence of the drug’s mechanism of action.
4. Safety Profile: Adrabetumlimab has demonstrated a manageable safety profile in clinical trials, with most adverse events being mild to moderate in severity. Ongoing monitoring for potential long-term effects is, of course, essential.

The Role of PCSK9 Inhibition in NPC Pathophysiology

Dr. Gold emphasized the rationale behind targeting PCSK9 in NPC. The underlying defect in NPC disrupts lipid trafficking, leading to cholesterol accumulation. Increasing LDL receptor levels through PCSK9 inhibition offers a potential pathway to restore some degree of lipid homeostasis. This approach addresses a core pathological mechanism of the disease, rather than simply managing symptoms.

Clinical Trial Details & Patient selection

the clinical trials evaluating adrabetumlimab included infants with confirmed infantile-onset NPC. Patients were carefully selected based on genetic confirmation of the disease and the presence of specific clinical features.The trials were designed to assess the drug’s safety, tolerability, and efficacy over a defined period.

* Trial Design: Typically involved open-label studies with a cohort of patients receiving adrabetumlimab.

* Assessment Tools: Neurological assessments (e.g., the NPC severity Scale), MRI imaging to monitor brain changes, liver volume measurements, and biomarker analysis were used to track disease progression.

* patient Age: Infants diagnosed with NPC before the age of two years were generally included in the trials.

Future Directions & Ongoing research

Dr. Gold noted that research is ongoing to further refine the use of adrabetumlimab in NPC. Areas of focus include:

* Optimizing Dosage: Determining the optimal dose and frequency of adrabetumlimab administration to maximize efficacy and minimize side effects.

* Combination Therapies: Investigating the potential benefits of combining adrabetumlimab with other therapies targeting different aspects of NPC pathophysiology.

* Long-Term Outcomes: Conducting long-term follow-up studies to assess the durability of the treatment effect and identify any late-onset adverse events.

* Expanding access: Working to ensure that adrabetumlimab is accessible to all patients who could benefit from this therapy.

Implications for NPC Management

Adrabetumlimab represents a significant advancement in the treatment of infantile-onset NPC. While not a cure, it offers the potential to slow disease progression and improve the quality of life for affected children. The insights shared by Dr. Alexander Gold through NeurologyLive