NCT04887311

MBM-01 (Tempol) for the Treatment of Ataxia Telangiectasia

An Open Label Study to Assess the Safety and Efficacy of MBM-01 for the Treatment of Ataxia Telangiectasia

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Matrix Biomed, Inc. · Industry
• Sex: All
• Age: 4 Years
• Healthy volunteers: Not accepted

Summary

Ataxia Telangiectasia (A-T) is an autosomal recessively inherited neurodegenerative disorder that also has dramatic effects on the immune and endocrine systems. The disorder results from mutations in the A-T mutated gene (ATM) leading to a loss in the production of the ATM protein. The active compound in MBM-01 (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) may substitute for the loss of ATM by protecting cells from DNA damage, preventing and reducing oxidative damage, triggering an increase in cellular survival proteins, and preserving the brain and peripheral immune system.

Detailed description

Cells lacking ATM are left defenseless and unable to repair cellular damaged DNA, to exhibit normal cell cycle control, to effectively respond to oxidative damage, ionizing radiation, and, alkylating agents, and to maintain a healthy immune response among others. A-T patients have increased oxidative stress and significantly reduced total antioxidant levels. In an early study directed to oxidative stress in A-T patients, a decrease in the levels of total antioxidant capacity has been observed. There is currently no cure for A-T, and current treatments are limited to palliative care. Therapies include rehabilitative care, infection prevention and treatment, and screening for pulmonary dysfunction and malignancies. Symptomatic treatments generally fall short and leave A-T patients debilitated and in a progressively wasting state. Patients suffering from A-T are in dire need of a treatment to alleviate the conditions of this disease. A drug product that can substitute for the loss of ATM has the potential to provide these patients with this critically unmet need. The active compound in MBM-01 has been shown to supplant the overall role of ATM by reducing oxidative stress, reducing DNA double strand breaks, and decreasing programmed cell death (in healthy cells). Accordingly, MBM-01 represents a potential breakthrough therapy for patients afflicted with A-T providing a multifactorial approached as evidenced by the following: 1. Doubling the lifespan of otherwise short lived ATM-deficient mice ; 2. Increasing NAD+, thereby decreasing the premature aging of A-T patients by reducing the severity of A-T neuropathology, normalizing neuromuscular function, delaying memory loss, and extending lifespan; 3. Increasing the transcription factor BDNF and NRF2 to decrease neurodegeneration and activate cellular defense machinery via antioxidant genes; 4. Maintaining and improving immune system function to ameliorate A-T symptoms ; 5. Protecting DNA from damage and repairing the type of DNA damage observed in A-T patients; 6. Preventing and reducing the type of oxidative stress observed in A-T patients; 7. Increasing the lifespan of mice under various conditions and toxicities; and 8. Decreasing tumorigenesis and carcinogenesis in general. The study is a multi-center open label study to assess the efficacy of MBM-01 to treat ataxia telangiectasia. Patients will be assessed during three study phases: a baseline period, a 9-month treatment period, and a 3-month follow-up period. Patients will visit sites day 0, month 3, month 6, and month 9 for safety labs and efficacy assessments. Dosing will follow a weight-tiered dosing schedule administered orally QD via premarked medicine cups. Patients will be administered study drug daily, 7-days a week. The patients will be placed into one of four dosing groups.

Conditions

• Ataxia Telangiectasia Louis-Bar
• Ataxia Telangiectasia in Children
• Ataxia Telangiectasia

Interventions

Type	Name	Description
DRUG	MBM-01	Patients will be administered study drug daily for 9 months QD via premarked medicine cups.

Timeline

• Start date: 2021-07-01
• Primary completion: 2022-06-01
• Completion: 2022-12-01
• First posted: 2021-05-14
• Last updated: 2021-05-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study