US 12,111,308 B2
Biomarker platform for Parkinson's disease using patient-derived primary dermal fibroblasts
Lalitha Madhavan, Tucson, AZ (US)
Assigned to ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIVERSITY OF ARIZONA, Tucson, AZ (US)
Filed by ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIVERSITY OF ARIZONA, Tucson, AZ (US)
Filed on Jan. 12, 2021, as Appl. No. 17/147,022.
Application 17/147,022 is a continuation of application No. 16/162,242, filed on Oct. 16, 2018, granted, now 11,099,173.
Claims priority of provisional application 62/572,933, filed on Oct. 16, 2017.
Prior Publication US 2021/0132046 A1, May 6, 2021
Int. Cl. G01N 33/50 (2006.01); C12N 5/071 (2010.01)
CPC G01N 33/5091 (2013.01) [C12N 5/0625 (2013.01); G01N 33/5044 (2013.01); G01N 2800/2835 (2013.01); G01N 2800/52 (2013.01); G01N 2800/60 (2013.01); G01N 2800/7009 (2013.01)] 6 Claims
 
1. A method of screening and identifying a drug suitable for treating Parkinson's disease (PD), the method comprising:
a) obtaining a skin fibroblast sample from a subject diagnosed with PD;
b) growing said skin fibroblast samples in a medium;
c) generating a PD biomarker profile of said skin fibroblast sample comprising; determining fibroblast growth rate, cell density, cell size and shape, viability, the level of oxidative stress, the level of mitochondria, mitochondrial fragmentation, and/or the level of autophagic vesicles of said skin fibroblast sample;
d) administering the drug to the PD fibroblast sample and generating a drug-treated PD biomarker profile as in c); and
e) comparing the drug-treated PD biomarker profile to the PD biomarker profile
wherein the drug is identified as suitable for treating PD when the comparison of the PD biomarker profile against the drug-treated PD biomarker profile results in the following:
i) the drug-treated PD skin fibroblasts have a slower growth rate than the PD skin fibroblasts;
ii) the drug-treated PD skin fibroblasts have a decreased cell density than the PD skin fibroblasts;
iii) the drug-treated PD skin fibroblasts are larger and less circular than the PD skin fibroblasts;
iv) the drug-treated PD skin fibroblasts have a lower total reactive oxygen species (ROS) production and a lower mitochondrial ROS than the PD skin fibroblasts;
v) the drug-treated PD skin fibroblasts have an increase in respiratory control rate (RCR) than the PD skin fibroblasts;
vi) the drug-treated PD skin fibroblasts have a decreased proton leak than the PD skin fibroblast;
vii) the drug-treated PD skin fibroblasts have an increase in mitochondria than the PD skin fibroblast;
viii) the drug-treated PD skin fibroblasts have a decrease in mitochondrial fragmentation than the PD skin fibroblast; or
ix) the drug-treated PD skin fibroblasts have a decrease in autophagic vesicles than the PD skin fibroblasts.