Objective: 1: to identify and measure endogenous CDNF levels in peripheral whole blood of healthy control subjects and to examine CNDF  expression development profile across the life span of humans ; 2: to investigate differential CNDF mRNA expresion in whole blood, platelets and lymphocytes and whether the  changes in CNDF expression is specific for  PD subjects  

Background: There is  growing evidence for the neuroprotective and neurorestorative effects of CDNF  secreted by the endoplasmic reticulum selective for dopamine (DA) neurons. CDNF modulate neuroinflamamtion, protein folding and mitigates excessive ER stress and faciliates alpha-synclein aggregates clearance. CDNF infusion rescues behavioral neural repair in PD.

Methods: Part 1)For characterizing CDNF development , we recruited three groups of healthy controls: 1) children ( 1-18 yrs : 2) adults ( 18-50 yrs); 3)elderly adults (> 50 yrs).  Part 2)For PD subjects, we recruited PD subjects diagnosed by research neurologists ,along with normal age-matched healthy subjects and stroke patients. Venous blood was collected , lymphocytes and platelets were isolated for  RNA extraction for reversed transcriptase rRT-PCR assays for both Part 1 and part 2.

Results: We found a statistically significant ( p< 0.05, one-way ANOVA ; Tukey ;posthoc test)  decrease in CDNF mRNA exprssion in whole blood in the transition from the childhood/adolescence [ n=7 ] to the yound adulthood [ n=22 ] , with progressive trend of significant decline in CDNF from childhood to elderly group [ n=16 mean age 63 yrs] (p< 0.05), suggesting  downregulation of  CDNF mRNA expression with aging. We found that a significant increase in CDNF mRNA expression in PD patients [ n=13  mean age: 72.8 yrs] compared with stroke patients [n=8 mean age: 71.5 yrs].and normal healthy control subjects [ n=15, mean age: 66.8 yrs] , as determined by one-way ANOVA (F(2,33)=4.89, p , 0.014) across the three groups. .No significant difference was found in the lymphocytes. Whole blood CDNF mRNA was reduced in stroke patients compared with control but not for PD patients.

Conclusions: Our findings of specific paradoxical increase in platelet CDNF mRNA expression for PD ,and  decline of CDNF mRNA with age, suggest compensatory CDNF to counteract ER stress  may be the emerging  potential therapeutic target in PD.

References: Lindholm P, Voutilainen MH , Lauren J, Peranen J et al Novel neurotrophic factor CDNF protects and rescues midbrain dopamien neurons in vivo. Nature 2007 448(5): 73-78

Lindahl, M, Saarma M, P Lindholm: Unconventional neurotrophic factors: CDNF MANF , sturcture physiolgoical functions and therapeutic potentials. Neuro. Dis. 2017  97: 90-102

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MDS Abstracts - https://www.mdsabstracts.org/abstract/exploratory-clinical-study-of-role-of-cerebral-dopamine-neurotrophic-factor-cdnf-mediating-endoplasmic-reticulum-stress-ers-in-parkinson-disease/