Sulfopropanoic acid derivatives for treating neurodegenerative disorders: a patent spotlight

Abstract

The patent introduces a class of agents that target amyloid aggregation, and subsequently, reduce amyloid β-oligomer neurotoxicity. The class encompasses sulfopropanoic acid derivatives and is represented by tramiprosate and its prodrug ALZ-801 (valiltramiprosate). Clinical trials showed that ALZ-801 oral tablet is well tolerated and showed superior pharmacokinetic properties in healthy volunteers and Alzheimer's disease (AD) patients. Results from phase II & III trials of ALZ-801 in early AD have provided evidence of efficacy and to adjudicate the role of amyloid β-oligomers in AD pathogenesis. The confirmatory APOLLOE4 phase III trial of ALZ-801 in APOE4/4 homozygotes with early AD has been initiated. If ALZ-801 is approved, it will be among the first oral disease-modifying drugs for AD.

Article highlights

Background

• Anti-amyloid antibodies show promise as disease-modifying treatments. Yet, they are associated with a risk of ARIA-E, requiring MRI monitoring, which is burdensome in the elderly population and could limit their utility in clinical practice.

• Aβ42 oligomers are the key drivers of AD pathogenesis and increased concentration of Aβ42 oligomers correlates closely with the onset and progression of clinical symptoms.

• An inverse correlation between cognitive impairment severity and the concentration of 3-SPA was identified in subjects having mild to moderate AD.

The potential new treatments

• 3-SPA and tramiprosate inhibit the aggregation of Aβ42 oligomers.

Discussion

• Increasing 3-SPA CSF levels to above those found in AD subjects is expected to protect those subjects from further cognitive decline or reduce the rate of cognitive decline.

Conclusion

• Compounds (formula I) that are metabolized to 3-SPA, and therefore increase 3-SPA CSF levels, are claimed to help subjects suffering from Alzheimer's disease, dementia, or cognitive decline.

Keywords: :

• Alzheimer's disease
• Aβ-oligomerization
• tramiprosate
• valiltramiprosate ALZ-801

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.