Targeted Plasmalogen Supplementation: Effects on Blood Plasmalogens, Oxidative Stress Biomarkers, Cognition, and Mobility in Cognitively Impaired Persons.

Plasmalogens are a specific type of glycerophospholipid found in especially high levels in neuronal membranes. Decreased blood and brain levels of docosahexaenoic acid (DHA) containing plasmalogens are associated with decreased cognition and neuromuscular function in humans. Administration of 1-O-alkyl-2-acylglycerol (AAG) plasmalogen precursors containing DHA at the sn-2 position dose-dependently increase blood DHA plasmalogens and are neuroprotective in animal models of neurodegeneration at doses between 10 and 50 mg/kg. We conducted an investigational clinical trial in 22 cognitively impaired persons to evaluate the effects of an escalating oral dosing regimen of DHA-AAG from 900 to 3,600 mg/day over a 4-month period on blood serum plasmalogen and non-plasmalogen phospholipids and oxidative stress biomarkers. Safety, tolerability and therapeutic effects on cognition and mobility were also evaluated. DHA plasmalogen levels increased with increasing dose and remained significantly elevated at all treatment doses and durations. DHA plasmalogen levels were positively associated with catalase activity and negatively associated with malondialdehyde (MDA) levels. DHA-AAG supplementation normalized catalase activity in persons with low baseline catalase activity, normalized MDA levels in persons with high baseline MDA levels, and normalized superoxide dismutase activity in persons with high baseline SOD activity. Cognition improved in nine participants, was unchanged in nine, and declined in four. Mobility improved in twelve, was unchanged in five and declined in four participants. Changes in cognition and mobility were statistically significant versus a random outcome. Baseline DHA-plasmalogen levels were not predictive of clinical response. DHA-AAG was well tolerated at all dosages and no adverse reactions were observed.

Noninvasive Delivery of Biologicals to the Brain.

In the past, psychotherapy and neuropharmacological approaches have been the most common treatments for disordered thoughts, moods, and behaviors. One new path of brain therapeutics is in the deployment of noninvasive approaches designed to reprogram brain function at the cellular level. Treatment at the cellular level may be considered for a wide array of disorders, ranging from mood disorders to neurodegenerative disorders. Brain-targeted biological therapy may provide minimally invasive and accurate delivery of treatment. The present article discusses the hurdles and advances that characterize the pathway to this goal.

Safety and Efficacy of Platelet Rich Plasma for Treatment of Lumbar Discogenic Pain: A Prospective, Multicenter, Randomized, Double-blind Study.

BACKGROUND: Interventions for chronic discogenic spine pain are currently insufficient in lowering individual patient suffering and global disease burden. A 2016 study of platelet rich plasma (PRP) for chronic discogenic pain previously demonstrated clinically significant response among active group patients compared with controls. OBJECTIVES: To replicate the previous research to move this intervention forward as a viable option for patient care. STUDY DESIGN: A double-blind, randomized, placebo-controlled study. SETTING: Multicenter private practices. METHODS: Twenty-six (12 men, 14 women) human patients, ages 25 to 71 with a diagnosis of chronic lumbar discogenic pain, were randomly assigned to active (PRP) or control (saline) groups in a ratio of 2 active to 1 control. Baseline and follow-up Oswestry Disability Index and Numeric Pain Rating Scale questionnaires were obtained to track patient outcomes at 8 weeks postoperatively. RESULTS: Within group assessment showed clinically significant improvement in 17% of PRP patients and clinically significant decline in 5% (1 patient) of the active group. Clinically significant improvement was seen in 13% of placebo group patients and no placebo patients had clinically significant decline secondary to the procedure. LIMITATIONS: Possible explanations may include a range of factors including differences in patient demographics, outcome-measure sensitivity, or misalignment of statistical analyses. CONCLUSIONS: These findings are markedly different than the highly promising results of the 2016 PRP study. This study posits necessary caution for researchers who wish to administer PRP for therapeutic benefit and may ultimately point to necessary redirection of interventional research for discogenic pain populations.

Transcranial Infrared Laser Stimulation for the Treatment of Traumatic Brain Injury: A Case Series.

Introduction: This study intended to evaluate the safety and possible therapeutic effect of transcranial infrared laser stimulation (TILS) based on photobiomodulation (PBM) among patients with traumatic brain injury (TBI). Methods: Eleven participants who were diagnosed with TBI after full neurological examination and MRI evaluation by a board-certified neurologist completed five to eight 20-minute TILS sessions using the Cytonsys CytonPro-5000 apparatus (pilot laser control, focused wavelength of 1064 nm, maximum output power of 10W, maximum optical power density of 500 mW/cm2, effective area 4.5 cm2 in diameter). Per TILS session, participants underwent a laser dose of 250 mW/cm2 continuous laser wave to each hemisphere using predetermined patient-specific coordinates. Structural imaging was used to neuronavigate individual treatment targets in the frontal cortex (Brodmann area 10). The primary safety measure for this study was the occurrence of adverse events (AEs) or serious adverse events (SAEs). The primary efficacy outcome measure was the participant-rated global rating of change (GRC) post-intervention. Secondary outcome measures included a battery of neuropsychological testing and mood questionnaires done both pre- and post-intervention. Results: All patients enrolled in this study protocol were able to tolerate the study procedures without any AEs or SAEs. Nine out of eleven participants had clinically significant improvements in GRC score (≥ +2). Neuropsychological testing and mood questionnaire outcomes also suggested a positive therapeutic effect. Conclusion: This study provides preliminary evidence supporting the safety and potential efficacy of TILS as a non-invasive clinical intervention for individuals with TBI.