New insights into clinical trial for colostrinin™ in Alzheimer's disease

P. Szaniszlo, P. German, G. Hajas, D. N. Saenz, M. Kruzel, Istvan Boldogh

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: The pathomechanism of Alzheimer's disease (AD) is multifactorial although the most popular hypotheses are centered on the effects of the misfolded, aggregated protein, amyloid beta (Aβ) and on Tau hyperphosphorylation. Objectives: Double blinded clinical trials were planned to demonstrate the effect of Colostrinin™ (CLN) on instrumental daily activities of AD patients. The potential molecular mechanisms by which CLN mediates its effects were investigated by gene expression profiling. Methods: RNAs isolated from CLN-treated cells were analyzed by high-density oligonucleotide arrays. Network and pathway analyses were performed using the Ingenuity Pathway Analysis software. Results: The Full Sample Analysis at week 15 showed a stabilizing effect of CLN on cognitive function in ADAS-cog (p = 0.02) and on daily function in IADL (p = 0.02). The overall patient response was also in favor of CLN (p = 0.03). Patients graded as mild on entry also showed a superior response of ADAS-cog compared to more advanced cases (p = 0.01). Data derived from microarray network analysis show that CLN elicits highly complex and multiphasic changes in the cells' transcriptome. Importantly, transcriptomal analysis showed that CLN alters gene expression of molecular networks implicated in Aβ precursor protein synthesis, Tau phosphorylation and increased levels of enzymes that proteolitically eliminate Aβ. In addition, CLN enhanced the defense against oxidative stress and decreased expression of inflammatory chemokines and cytokines, thereby attenuating inflammatory processes that precede Alzheimer's and other neurological diseases. Conclusion: Together these data suggest that CLN has promising potential for clinical use in prevention and therapy of Alzheimer's and other age-associated central nervous system diseases.

Original languageEnglish (US)
Pages (from-to)235-241
Number of pages7
JournalJournal of Nutrition, Health and Aging
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2009

Keywords

  • AD
  • CLN
  • Network analysis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Geriatrics and Gerontology

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