SUN13837 in Treatment of Acute Spinal Cord Injury, the ASCENT-ASCI Study
Benjamin Levinson,
James Lee,
Hubert Chou,
Dennis Maiman
Issue:
Volume 2, Issue 1, March 2018
Pages:
1-8
Received:
26 October 2017
Accepted:
8 November 2017
Published:
23 December 2017
Abstract: The purpose of this study was to assess the safety and efficacy of SUN13837, a bFGF mimetic, for the treatment of acute cervical spinal cord injury. In a 26-week, double-blind trial, 65 subjects were randomized (1:1) by stratum within 12 hours of injury to 1 mg/kg/day of intravenous SUN13837 (SUN) or matching placebo (pbo) for no less than 7 and no more 28 days. The efficacy measures at Week 16 were the mean total SCIM III (primary), combined SCIM III Self-Care and Mobility subscales (secondary) and ISNCSCI Total Motor scores (secondary). Of the 61 subjects who received study drug, 57 received at least 7 doses. 55 subjects (ITT population) were assessed by treatment assignment and by strata of C4-C5 AIS A (pbo=13, SUN=15), C6-C7 AIS A (pbo=6, SUN=5) or C3-C8 AIS B and C (pbo=9, SUN=7). The majority of subjects were Male (85.2%), Caucasian (63.9%). The Total SCIM III score between the 2 treatment groups at Week 16 was 4.54 (SE = 6.524), not statistically significant with p = 0.4912. Therefore, the primary end-point was not reached. Overall, larger effects were observed in AIS C6-C7 and AIS B and C strata as compared with AIS A C4-C5. Specifically, in the C3-8 AIS B and C stratum, a 6.8-point difference (LS) in Total SCIM III was observed (SUN vs. pbo). However, there were more AIS C subjects in the SUN (n=5) vs. pbo (n=2). The combination of self-care and mobility scores was not statistically significant with p-value = 0.3951. By Week 16, the LS Mean (SE) change from baseline in UEMS scores was 9.92 in SUN13837-treated subjects compared to 4.95 in Placebo-treated subjects (p-value = 0.0347). The largest treatment difference was seen in the AIS B and C strata in which SUN13837-treated subjects had an average change from baseline in UEMS of 25.40 compared to 6.86 in Placebo-treated subjects. As a result, the AIS B and C stratum may have contributed heavily to the overall treatment effect on the UEMS with lesser contribution by AIS A C4-C5 and C6-C7 strata. Analyses of primary and secondary outcomes showed non-significant trends consistently favoring SUN13837 treatment. The efficacy signal of SUN13837 warrants further investigation. No safety concerns were noted by an Independent Data Safety Monitoring and Review Board. Pharmacokinetic modeling indicates that the dose may need to be lowered in any further evaluation of SUN13837 (NCT01502631).
Abstract: The purpose of this study was to assess the safety and efficacy of SUN13837, a bFGF mimetic, for the treatment of acute cervical spinal cord injury. In a 26-week, double-blind trial, 65 subjects were randomized (1:1) by stratum within 12 hours of injury to 1 mg/kg/day of intravenous SUN13837 (SUN) or matching placebo (pbo) for no less than 7 and no...
Show More
Skin Picking in Individuals with Intellectual DisabilitySkin Picking in Individuals with Intellectual Disability
Issue:
Volume 2, Issue 1, March 2018
Pages:
9-11
Received:
5 August 2017
Accepted:
20 November 2017
Published:
9 January 2018
Abstract: Individuals with Intellectual Disability seek treatment from primary care physicians, neurologists, and psychiatrists for excoriation disorder, a disorder described as the picking of ones’ skin resulting in sores. There is a significant financial and emotional cost to people with this disorder. There is a lack of research in the area of co-occurring ID/D and excoriation disorder. This case series seeks to fill a gap in the literature by describing three distinct, successful treatments of excoriation disorder in individuals with intellectual disability.
Abstract: Individuals with Intellectual Disability seek treatment from primary care physicians, neurologists, and psychiatrists for excoriation disorder, a disorder described as the picking of ones’ skin resulting in sores. There is a significant financial and emotional cost to people with this disorder. There is a lack of research in the area of co-occurrin...
Show More
Neuroprotective and Therapeutic Role of Omega-3 Against Oxidative Stress and Neurotransmitter Disturbances in Rotenone-Induced Mice Model of Parkinson's Disease
Nagi Ali Ibrahim,
Yasser Ashry Khadrawy,
Soliman Sayed Ibrahim,
Noura El-Sayed Ezzat
Issue:
Volume 2, Issue 1, March 2018
Pages:
12-22
Received:
16 November 2017
Accepted:
5 December 2017
Published:
7 February 2018
Abstract: The present study aimed at evaluating the protective and therapeutic efficacy of omega-3 against motor impairment and brain biochemical disturbances in rotenone-induced mice model of Parkinson's disease (PD). Sixty animals were divided into six groups (10 each): mice of the 1st group were used as controls, they were injected subcutaneously ( s c ) with the vehicle (50 µl dimethylsulfoxide (DEMSO) + 950 µl sunflower oil /kg body weight) every other day for 30 days; the 2nd group, mice model of Parkinson’s disease (PD), were injected (s c ) with rotenone (3 mg/kg dissolved in vehicle every other day for 30 days ). the 3rd group, mice were given rotenone for 30 days followed by a stopping (recovery) period of other 30 days to validate the persistency of the PD model; the 4th group (protection group), mice received orally Omega-3 oil (300 mg/kg) daily an hour before every rotenone injection for 30 days; the 5th and 6th groups (therapeutic groups ), mice were treated orally with Omega-3 oil daily for 7 and 15 days respectively after the induction of PD mice model. Data obtained revealed an impairment of the motor activity in mice of PD model as indicated from the decreased time of the forelimb hanging test. This was associated with a state of oxidative stress in the brain of PD model as indicated from the increase in lipid peroxidation (increased malondialdehyed, MDA, level) and nitric oxide (NO), and the decrease in reduced glutathione (GSH). A significant decrease in the levels of dopamine, norepinephrine, serotonin, AChE activity and a significant increase in TNF-α level was recorded in the PD model. The present findings show that both the protection by or oral treatment with omega-3 for 15 days could ameliorate the rotenone- induced oxidative stress and inflammation in brain of PD mice model. In addition, omega-3 either as protection or treatment daily for 15 days was effective in restoring the decrease in dopamine and norepinephrine induced in the brain of PD mice model. In conclusion, the present study demonstrates that omega-3 supplementation potentially reverses the motor, and neurochemical alternations induced by rotenone in mice model of PD.
Abstract: The present study aimed at evaluating the protective and therapeutic efficacy of omega-3 against motor impairment and brain biochemical disturbances in rotenone-induced mice model of Parkinson's disease (PD). Sixty animals were divided into six groups (10 each): mice of the 1st group were used as controls, they were injected subcutaneously ( s c ) ...
Show More
