New insights into clinical trial for Colostrinin in Alzheimer's disease.
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 (Abeta) and on Tau hyperphosphorylation.


OBJECTIVE
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 Abeta precursor protein synthesis, Tau phosphorylation and increased levels of enzymes that proteolitically eliminate Abeta. 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.


CONCLUSIONS
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.
Szaniszlo
P
P
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA.
German
P
P
Hajas
G
G
Saenz
D N
DN
Kruzel
M
M
Boldogh
I
I
D000203:Activities of Daily Living; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010455:Peptides / Q000627:therapeutic use*; D012720:Severity of Illness Index
D036341:Intercellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D010455:Peptides; C105874:colostrinine