Loop, M. S. | Search bioRxiv

bioRxiv2022

Using Extracellular Vesicles Released by GDNF-transfected Macrophages for Therapy of Parkinson's Disease

Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids and genetic material playing important roles in intracellular communication. They have a remarkable potential as non-toxic and non-immunogenic nanocarriers for drug delivery to unreachable organs and tissues, in particular, the central nervous system (CNS). Herein, we developed a novel platform based on macrophage derived EVs to treat Parkinsons disease (PD). Specifically, we evaluated the therapeutic potential of EVs secreted by autologous macrophages that were transfected ex vivo to express glial cell line-derived neurotrophic factor (GDNF). EV-GDNF were collected from conditioned media of GDNF-transfected macrophages and characterized for GDNF content, size, charge, and expression of EV-specific proteins. The data revealed that along with the encoded neurotrophic factor, EVs released by pre-transfected macrophages carry GDNF-encoding DNA. Four months-old transgenic Parkin Q311(X)A mice were treated with EV-GDNF via intranasal administration, and the effect of this therapeutic intervention on locomotor functions was assessed over a year. Significant improvements in mobility, increase in neuronal survival, and decrease in neuroinflammation were found in PD mice treated with EV-GDNF. No offsite toxicity caused by EV-GDNF administrations was detected. Overall, EV-based approach can provide a versatile and potent therapeutic intervention for PD.

bioengineering↗

bioRxiv2019

Patterns of Treatment in Patients with Heart Failure with Preserved Ejection Fraction: the REasons for Geographic And Racial Differences in Stroke study

PurposeWe described medication use patterns among REasons for Geographic And Racial Differences in Stroke (REGARDS) participants hospitalized for heart failure with preserved ejection fraction (HFpEF) (152 hospitalizations, 101 unique individuals).\n\nMethodsMedication data were obtained from medical record review and Medicare Part D pharmacy claims. We compared discharge medication prescriptions between patients with and without chronic kidney disease (CKD), coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), and diabetes.\n\nResultsThe mean age was 74.8 years, 53.3% were black and 73.7% were female. Hypertension (97.2%), diabetes (65.1%), COPD (51.3%), CKD (41.1%) and history of CHD (60.9%) were common. On admission and discharge, respectively, beta-blockers (66.4%, 72.7%), angiotensin converting enzyme inhibitors or angiotensin receptor blockers (42.8%, 51.7%), diuretics (61.2%, 80.9%), loop diuretics (55.9%, 78.3%), calcium channel blockers (41.0%, 41.2%) and statins (44.7%, 50.3%) were commonly used. Spironolactone, digoxin, hydralazine plus isosorbide dinitrate (HISDN), isosorbide dinitrate alone and aldosterone receptor antagonists were used by <20%. For each medication, prescriptions were more common at discharge than admission. Many participants did not have Medicare claims for filled prescriptions in the year following discharge. A higher percentage of patients with versus without CKD, CHD, and diabetes had discharge prescriptions statins. Participants with CKD were also more likely to receive prescriptions for HISDN.\n\nConclusionBeta-blockers and diuretics were commonly prescribed at admission and discharge among HFpEF, but pharmacy claims for these medications within one-year were substantially less common. The comorbidities CHD, CKD, and diabetes were associated with prescriptions of statins at discharge.

epidemiology↗