Small molecule targeting long noncoding RNA GAS5 administered intranasally improves neuronal insulin signaling and decreases neuroinflammation in an aged mouse model.

Shifts in normal aging set stage for neurodegeneration and dementia affecting 1 in 10 adults. The study demonstrates that lncRNA GAS5 is decreased in aged and Alzheimer's disease brain. The role and targets of lncRNA GAS5 in the aging brain were elucidated using a GAS5-targeting small molecule NPC86, a frontier in lncRNA-targeting therapeutic. Robust techniques such as molecular dynamics simulation of NPC86 binding to GAS5, in vitro functional assays demonstrating that GAS5 regulates insulin signaling, neuronal survival, phosphorylation of tau, and neuroinflammation via toll-like receptors support the role of GAS5 in maintaining healthy neurons. The study demonstrates the safety and efficacy of intranasal NPC86 treatment in aged mice to improve cellular functions with transcriptomic analysis in response to NPC86. In summary, the study demonstrates that GAS5 contributes to pathways associated with neurodegeneration and NPC86 has tremendous therapeutic potential to prevent the advent of neurodegenerative diseases and dementias.

Intranasal delivery of exosomes from human adipose derived stem cells at forty-eight hours post injury reduces motor and cognitive impairments following traumatic brain injury.

The neuroprotective role of human adipose-derived stems cells (hASCs) has raised great interest in regenerative medicine due to their ability to modulate their surrounding environment. Our group has demonstrated that exosomes derived from hASC (hASCexo) are a cell-free regenerative approach to long term recovery following traumatic brain injury (TBI). Previously, we demonstrated the efficacy of exosome treatment with intravenous delivery at 3 h post TBI in rats. Here, we show efficacy of exosomes through intranasal delivery at 48 h post TBI in mice lengthening the therapeutic window of treatment and therefore increasing possible translation to clinical studies. Our findings demonstrate significant recovery of motor impairment assessed by an elevated body swing test in mice treated with exosomes containing MALAT1 compared to both TBI mice without exosomes and exosomes depleted of MALAT1. Significant cognitive improvement was seen in the reversal trial of 8 arm radial arm water maze in mice treated with exosomes containing MALAT1. Furthermore, cortical damage was significantly reduced in mice treated with exosomes containing MALAT1 as well as decreased MHCII+ staining of microglial cells. Mice without exosomes or treated with exosomes depleted of MALAT1 did not show similar recovery. Results demonstrate both inflammation related genes and NRTK3 (TrkC) are target genes modulated by hASC exosomes and further that MALAT1 in hASC exosomes regulates expression of full length TrkC thereby activating the MAPK pathway and promoting recovery. Exosomes are a promising therapeutic approach following TBI with a therapeutic window of at least 48 h and contain long noncoding RNA's, specifically MALAT1 that play a vital role in the mechanism of action.

Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades.

Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.

T cell infiltration and upregulation of MHCII in microglia leads to accelerated neuronal loss in an α-synuclein rat model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most prevalent movement disorder characterized by up to 80% loss of dopamine (DA) neurons and accumulation of Lewy body deposits composed of α-synuclein (α-syn). Accumulation of α-syn is associated with microglial activation, leading to a pro-inflammatory environment linked with the pathogenesis of PD. Along with microglia, CD4 and CD8 T cells are observed in SNpc. The contribution of T-cells to PD development remains unclear with studies demonstrating that they may mediate neurodegeneration or act in a neuroprotective manner. METHODS: Here, we assessed the contribution of T cells to PD neurodegeneration using an adeno-associated virus (AAV) coding human wild-type α-syn or GFP injected into the substantia nigra pars compacta (SNpc) in T cell deficient (athymic nude) and T cell competent (heterozygous) rats. The rats were behaviorally assessed with cylinder test to test paw bias. Following behavior testing, brains were collected and analyzed for markers of dopamine neuron, microglial activation, T cells, and α-syn expression. RESULTS: Injection of AAV9-α-syn unilaterally into the SN of T cell competent rats resulted in a significant paw bias in comparison to the controls at 60 days post-injection. Conversely, T cell-deficient rats injected with AAV9-α-syn showed no deficit in paw bias. As expected, injected T cell competent rats demonstrated a significant increase in microglial activation (MHCII staining) as well as significant dopaminergic neuron loss. In contrast, the T cell-deficient counterparts did not show a significant increase in microglial activation or significant neuron loss compared to the control animals. We also observed CD4 and CD8 T cells in SNpc following microglial MHCII expression and dopaminergic neuron loss. The time course of T cell entry correlates with upregulation of MHCII and the peak loss of TH+ cells in the SNpc. CONCLUSION: These data demonstrate that T cell infiltration and microglial upregulation of MHCII are involved in α-synuclein-mediated DA neuron loss in this rat model of PD.

Effects of nutraceutical intervention on serum proteins in aged rats.

Aging is associated with many pathophysiological changes that could lead to the onset of degenerative disease. Some of the physiological changes that occur with aging include increased inflammation and decreased stem cell proliferation, leading to decreased capacity for tissue regeneration and loss of function. In previous studies, we and others have found nutraceutical intervention to ameliorate some of the deleterious effects associated with aging. In particular, we have previously shown that NT-020, a supplement composed of a proprietary blend of blueberries, green tea, vitamin D3, and carnosine, is able to rescue age-related cognitive deficits, impaired neurogenesis, and inflammation in rats. We have also previously demonstrated that stem cells cultured with old serum showed decreased proliferation; however, when stem cells were cultured in serum from old rats given a diet supplemented with NT-020, proliferation did not differ from that of cells cultured with serum from young rats. While it is clear that NT-020 is exerting a therapeutic, anti-aging effect, the mechanisms of action were yet to be fully elucidated.To that end, in the present study, we conducted a bioinformatics experiment to examine the rat proteome of serum from young and old control rats and young and old rats given a diet supplemented with NT-020. Serum from old rats showed an increase in some inflammatory and pro-aging factors while serum from old rats given a diet supplemented with NT-020 showed an increase in some anti-aging factors, most notably proteins associated with the complement system and autophagy. A number of immune functions that increase with age were shown to be downregulated with NT-020 treatment.

Experimental and computational evidence for C=O π-bonding in [CH2OH]+ and related oxonium ions.

The question of whether [CH2OH]+ should be described as the hydroxymethyl cation, +CH2OH, or protonated formaldehyde, CH2=OH+, is reconsidered in the light of experimental information and new computational evidence. Previous arguments that the charge distribution in [CH2OH]+ may be probed by considering the incremental stabilisation of [CH2OH]+ induced by homologation on carbon (to give [CH3CHOH]+) or oxygen (to produce [CH2OCH3]+) are critically examined. Cation stabilisation energies are shown to be better indicators of the nature of these oxonium ions. Further insight into the structure of larger CnH2n+1O+ oxonium ions is obtained by considering the site of protonation of enol ethers and related species. Computational information, including AIM (Atoms and Molecules) and NBA (Natural Bond Analysis) charges on the carbon and oxygen atoms in [CH2OH]+ and related species, is considered critically. Particular attention is focused on the calculated bond lengths and barriers to rotation about the C-O bond(s) in [CH2OH]+, [CH3CHOH]+, [(CH3)2COH]+, CH3OH and [CH2OCH3]+ and the C-N bond in [CH2NH2]+. Trends in these data are consistent with appreciable π-bonding only in the C-O connections which correspond to the C=O bond in the parent aldehyde or ketone from which the oxonium ion may be considered to be derived by protonation or alkyl cationation.

Astaxanthin supplementation modulates cognitive function and synaptic plasticity in young and aged mice.

The incidence of neurodegenerative disorders and cognitive impairment is increasing. Rising prevalence of age-related medical conditions is associated with a dramatic economic burden; therefore, developing strategies to manage these health concerns is of great public health interest. Nutritionally based interventions have shown promise in treatment of these age-associated conditions. Astaxanthin is a carotenoid with reputed neuroprotective properties in the context of disease and injury, while emerging evidence suggests that astaxanthin may also have additional biological activities relating to neurogenesis and synaptic plasticity. Here, we investigate the potential for astaxanthin to modulate cognitive function and neural plasticity in young and aged mice. We show that feeding astaxanthin to aged mice for 1 month improves performance on several hippocampal-dependent cognitive tasks and increases long-term potentiation. However, we did not observe an alteration in neurogenesis, nor did we observe a change in microglial-associated IBA1 immunostaining. This demonstrates the potential for astaxanthin to modulate neural plasticity and cognitive function in aging.

Long noncoding RNA MALAT1 in exosomes drives regenerative function and modulates inflammation-linked networks following traumatic brain injury.

BACKGROUND: Neuroinflammation is a common therapeutic target for traumatic brain injury (TBI) due to its contribution to delayed secondary cell death and has the potential to occur for years after the initial insult. Exosomes from adipose-derived stem cells (hASCs) containing the long noncoding RNA MALAT1 are a novel, cell-free regenerative approach to long-term recovery after traumatic brain injury (TBI) that have the potential to modulate inflammation at the genomic level. The long noncoding RNA MALAT1 has been shown to be an important component of the secretome of hASCs. METHODS: We isolated exosomes from hASC containing or depleted of MALAT1. The hASC-derived exosomes were then administered intravenously to rats following a mild controlled cortical impact (CCI). We followed the rats with behavior, in vivo imaging, histology, and RNA sequencing (RNA Seq). RESULTS: Using in vivo imaging, we show that exosomes migrate into the spleen within 1 h following administration and enter the brain several hours later following TBI. Significant recovery of function on motor behavior as well as a reduction in cortical brain injury was observed after TBI in rats treated with exosomes. Treatment with either exosomes depleted of MALAT1 or conditioned media depleted of exosomes showed limited regenerative effects, demonstrating the importance of MALAT1 in exosome-mediated recovery. Analysis of the brain and spleen transcriptome using RNA Seq showed MALAT1-dependent modulation of inflammation-related pathways, cell cycle, cell death, and regenerative molecular pathways. Importantly, our data demonstrates that MALAT1 regulates expression of other noncoding RNAs including snoRNAs. CONCLUSION: We demonstrate that MALAT1 in hASC-derived exosomes modulates multiple therapeutic targets, including inflammation, and has tremendous therapeutic potential for treatment of TBI.

HIV Non-Nucleoside Reverse Transcriptase Inhibitor Efavirenz Reduces Neural Stem Cell Proliferation in Vitro and in Vivo.

The prevalence of HIV-associated neurocognitive disorders (HAND) remains high despite combination antiretroviral therapy (cART). There is evidence that neural stem cells (NSCs) can migrate to sites of brain injury such as those caused by inflammation and oxidative stress, which are pathological features of HAND. Thus, reductions in NSCs may contribute to HAND pathogenesis. Since the HIV non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) has previously been associated with cognitive deficits and promotion of oxidative stress pathways, we examined its effect on NSCs in vitro as well as in C57BL/6J mice. Here we report that EFV induced a decrease in NSC proliferation in vitro as indicated by MTT assay, as well as BrdU and nestin immunocytochemistry. In addition, EFV decreased intracellular NSC adenosine triphosphate (ATP) stores and NSC mitochondrial membrane potential (MMP). Further, we found that EFV promoted increased lactate dehydrogenase (LDH) release, activation of p38 mitogen-activated protein kinase (MAPK), and increased Bax expression in cultured NSCs. Moreover, EFV reduced the quantity of proliferating NSCs in the subventricular zone (SVZ) of C57BL/6J mice as suggested by BrdU, and increased apoptosis as measured by active caspase-3 immunohistochemistry. If these in vitro and in vivo models translate to the clinical syndrome, then a pharmacological or cell-based therapy aimed at opposing EFV-mediated reductions in NSC proliferation may be beneficial to prevent or treat HAND in patients receiving EFV.

NT-020 treatment reduces inflammation and augments Nrf-2 and Wnt signaling in aged rats.

BACKGROUND: Aging is associated with a decline in stem cell proliferation that is thought to be a result of dysregulated signaling in the neurogenic niche. This results in a diminished and less efficient pool of progenitors. The Wnt pathway plays a key role in the proliferation and differentiation of progenitor cells. Recent publications suggest that the age-related decline in the function of Wnt is a contributor to age-dependent decline in neural progenitors. Similarly, the aged neurogenic niche is characterized by higher levels of inflammatory cytokines. This increased inflammation contributes to the declining function of neural progenitor cells. NT-020, a proprietary blend of polyphenols, has been shown to increase proliferation of neural progenitors and improve cognitive function in aged rats. PURPOSE AND METHODS: In this study, we examined the neurogenic niche in the subgranular zone of the dentate gyrus (SGZ) and the subventricular zone (SVZ) of young and aged rats to determine if dietary supplementation with NT-020 could regulate inflammation and oxidative stress response pathways in neurons, astrocytes, and microglia. Further, we examined NT-020's ability to modulate Wnt signaling in the aged neurogenic niche. To accomplish this, we utilized gene PCR arrays and immunohistochemistry. RESULTS: We observed an increase in nuclear localization of immunopositive labeling of ß-catenin, HO-1, and Nrf2 in all subsets of cell types in both young and aged rats in the SGZ and SVZ following NT-020 treatment. NeuN-positive cells showed a basal increase in nuclear ß-catenin in the aged rats, which was not observed in doublecortin (DCX)-labeled cells, microglia, or astrocytes. Reverse transcription polymerase chain reaction (RT-PCR) analysis of isolated hippocampal tissue revealed that a significant percent of genes involved with inflammation are affected by treatment with NT-020. In addition, several genes that regulate Wnt activity were affected by supplementation. CONCLUSIONS: The results suggest that NT-020 activates oxidative stress response pathways and supports pro-neurogenic gene expression in the hippocampus. This may represent the mechanism by which the NT-020 formula enhances performance in learning and memory tasks in aged mice.

Anti-human α-synuclein N-terminal peptide antibody protects against dopaminergic cell death and ameliorates behavioral deficits in an AAV-α-synuclein rat model of Parkinson's disease.

The protein α-synuclein (α-Syn) has a central role in the pathogenesis of Parkinson's disease (PD) and immunotherapeutic approaches targeting this molecule have shown promising results. In this study, novel antibodies were generated against specific peptides from full length human α-Syn and evaluated for effectiveness in ameliorating α-Syn-induced cell death and behavioral deficits in an AAV-α-Syn expressing rat model of PD. Fisher 344 rats were injected with rAAV vector into the right substantia nigra (SN), while control rats received an AAV vector expressing green fluorescent protein (GFP). Beginning one week after injection of the AAV-α-Syn vectors, rats were treated intraperitoneally with either control IgG or antibodies against the N-terminal (AB1), or central region (AB2) of α-Syn. An unbiased stereological estimation of TH+, NeuN+, and OX6 (MHC-II) immunostaining revealed that the α-Syn peptide antibodies (AB1 and AB2) significantly inhibited α-Syn-induced dopaminergic cell (DA) and NeuN+ cell loss (one-way ANOVA (F (3, 30) = 5.8, p = 0.002 and (F (3, 29) = 7.92, p = 0.002 respectively), as well as decreasing the number of activated microglia in the ipsilateral SN (one-way ANOVA F = 14.09; p = 0.0003). Antibody treated animals also had lower levels of α-Syn in the ipsilateral SN (one-way ANOVA F (7, 37) = 9.786; p = 0.0001) and demonstrated a partial intermediate improvement of the behavioral deficits. Our data suggest that, in particular, an α-Syn peptide antibody against the N-terminal region of the protein can protect against DA neuron loss and, to some extent behavioral deficits. As such, these results may be a potential therapeutic strategy for halting the progression of PD.

Fractalkine over expression suppresses α-synuclein-mediated neurodegeneration.

In Parkinson's disease, α-synuclein is known to activate microglia and this activation has been proposed as one of the mechanisms of neurodegeneration. There are several signals produced by neurons that have an anti-inflammatory action on microglia, including CX3CL1 (fractalkine). We have shown that a soluble form of CX3CL1 is required to reduce neuron loss in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and that fractalkine agonism can reduce neuron loss in a 6-hydroxydopamine lesion model. Here, we show that fractalkine can reduce α-synuclein-mediated neurodegeneration in rats. Rats that received fractalkine showed abrogated loss of tyrosine hydroxylase and Neu-N staining. This was replicated in animals where we expressed fractalkine from astrocytes with the glial fibrillary acid protein (GFAP) promoter. Interestingly, we did not observe a reduction in MHCII expression suggesting that soluble fractalkine is likely altering the microglial state to a more neuroprotective one rather than reducing antigen presentation.

Hospital Dementia Services Project: aged care and dementia services in New South Wales hospitals.

AIMS: To describe the availability of aged care and dementia services in public hospitals in New South Wales (NSW), Australia in 2006/2007. METHOD: Hospitals were surveyed about issues relevant to dementia in acute care including the types of aged care wards and staff, policies, practices, clinics, community services and resources for dementia care. RESULTS: Responses were obtained from 163 hospitals (82%); responding hospitals represented 93.4% of NSW hospital beds, 96.7% of multiday episodes of care. Hospitals that had a Specialist Mental Health Service for Older People (SMHSOP) and an Aged Care Service (ACS) had the highest levels of dementia-related services and policies. Few hospitals without ACS or SMHSOP had clinics for dementia assessment, secure beds for disturbed behaviour, or services to manage patients with dementia and medical or behavioural comorbidity in the community. CONCLUSION: Dementia services in NSW hospitals are closely aligned with ACS and SMHSOP, with limited dementia services in hospitals without ACS or SMHSOP.

Characteristics of rural hospital services for people with dementia: findings from the Hospital Dementia Services Project.

OBJECTIVE: To obtain information about aged care services in rural New South Wales public hospitals, and to describe key operational aspects of their service delivery models. DESIGN: A mixed methods design was used to combine data collected from: (i) a survey of public hospitals and (ii) qualitative site visits in a sample of eleven rural sites. SETTING: Rural public hospitals in NSW, Australia. PARTICIPANTS: Qualitative data were collected from multidisciplinary clinicians, managers and community service providers who participated in site visits in 2010 and from surveys of NSW public hospitals in 2009/10 about aged care and dementia services. RESULTS: Survey and site visit findings demonstrated that rural hospitals have fewer secure beds for managing patients with disturbed behaviour due to dementia and delirium and fewer speciality aged care staff than metropolitan hospitals. Site visit participants also described how secure environments can aid care for people with dementia even in the absence of clinical specialists. CONCLUSION: The care of people with dementia in rural hospitals is constrained by access to specialist aged care staff and the physical environment of the hospital. Clinicians are adept at maximising resources to manage diagnosis and transitions for people with dementia. Further understanding of how key operational aspects of clinical leadership and environmental modifications impact on a range of patient outcomes would be valuable.

A spirulina-enhanced diet provides neuroprotection in an α-synuclein model of Parkinson's disease.

Inflammation in the brain plays a major role in neurodegenerative diseases. In particular, microglial cell activation is believed to be associated with the pathogenesis of neurodegenerative diseases, including Parkinson's disease (PD). An increase in microglia activation has been shown in the substantia nigra pars compacta (SNpc) of PD models when there has been a decrease in tyrosine hydroxylase (TH) positive cells. This may be a sign of neurotoxicity due to prolonged activation of microglia in both early and late stages of disease progression. Natural products, such as spirulina, derived from blue green algae, are believed to help reverse this effect due to its anti-inflammatory/anti-oxidant properties. An adeno-associated virus vector (AAV9) for α-synuclein was injected in the substantia nigra of rats to model Parkinson's disease and to study the effects of spirulina on the inflammatory response. One month prior to surgeries, rats were fed either a diet enhanced with spirulina or a control diet. Immunohistochemistry was analyzed with unbiased stereological methods to quantify lesion size and microglial activation. As hypothesized, spirulina was neuroprotective in this α-synuclein model of PD as more TH+ and NeuN+ cells were observed; spirulina concomitantly decreased the numbers of activated microglial cells as determined by MHCII expression. This decrease in microglia activation may have been due, in part, to the effect of spirulina to increase expression of the fractalkine receptor (CX3CR1) on microglia. With this study we hypothesize that α-synuclein neurotoxicity is mediated, at least in part, via an interaction with microglia. We observed a decrease in activated microglia in the rats that received a spirulina- enhanced diet concomitant to neuroprotection. The increase in CX3CR1 in the groups that received spirulina, suggests a potential mechanism of action.

CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity.

The protective/neurotoxic role of fractalkine (CX3CL1) and its receptor CX3C chemokine receptor 1 (CX3CR1) signaling in neurodegenerative disease is an intricate and highly debated research topic and it is becoming even more complicated as new studies reveal discordant results. It appears that the CX3CL1/CX3CR1 axis plays a direct role in neurodegeneration and/or neuroprotection depending on the CNS insult. However, all the above studies focused on the role of CX3CL1/CX3CR1 signaling in pathological conditions, ignoring the relevance of CX3CL1/CX3CR1 signaling under physiological conditions. No approach to date has been taken to decipher the significance of defects in CX3CL1/CX3CR1 signaling in physiological condition. In the present study we used CX3CR1⁻/⁻, CX3CR1⁺/⁻, and wild-type mice to investigate the physiological role of CX3CR1 receptor in cognition and synaptic plasticity. Our results demonstrate for the first time that mice lacking the CX3CR1 receptor show contextual fear conditioning and Morris water maze deficits. CX3CR1 deficiency also affects motor learning. Importantly, mice lacking the receptor have a significant impairment in long-term potentiation (LTP). Infusion with IL-1ß receptor antagonist significantly reversed the deficit in cognitive function and impairment in LTP. Our results reveal that under physiological conditions, disruption in CX3CL1 signaling will lead to impairment in cognitive function and synaptic plasticity via increased action of IL-1ß.

An open-label, multicenter study of the efficacy and safety of a weekday/weekend treatment regimen with calcitriol ointment 3 microg/g and clobetasol propionate spray 0.05% in the management of plaque psoriasis.

High-potency topical corticosteroids are the cornerstone of psoriasis therapy. Although highly effective, long-term use of topical steroids can cause adverse side effects. Additionally, steroids alone do not address the multiple pathophysiologic factors that cause the disease. Psoriasis regimens that utilize high-potency steroids combined with nonsteroid-containing products such as vitamin D analogs have been used for many years to manage the disease, not only for the short-term treatment of the disease but also for long-term treatment to minimize the recurrence of symptoms. We report an open-label, multicenter study designed to evaluate a weekday/ weekend treatment regimen involving calcitriol ointment 3 microg/g and clobetasol propionate spray 0.05% for moderate plaque psoriasis. Participants applied calcitriol ointment 3 microg/g twice daily on the weekdays and clobetasol propionate spray 0.05% twice daily on the weekends for up to 4 weeks. Participants were evaluated at baseline, week 2, and week 4. The results of this study demonstrate that a 4-week regimen of calcitriol ointment 3 microg/g treatment on weekdays and clobetasol propionate spray 0.05% on weekends is effective and well-tolerated for the treatment of moderate plaque psoriasis.

An open-label, multicenter study of the efficacy and safety of an AM/PM treatment regimen with clobetasol propionate spray 0.05% and calcitriol ointment 3 microg/g in the management of plaque psoriasis.

Psoriasis is a chronic condition with serious quality-of-life ramifications. Dermatologists seek alternative treatments of patients with plaque psoriasis that provide both efficacy and safety while minimizing exposure to high-potency steroids that can have adverse effects following long-term use. We report an open-label, multicenter study designed to evaluate a morning/evening (AM/PM) treatment regimen involving clobetasol propionate spray 0.05% and calcitriol ointment 3 microg/g for moderate plaque psoriasis. Participants applied clobetasol propionate spray 0.05% in the morning and calcitriol ointment 3 microg/g in the evening for up to 4 weeks. Participants were evaluated at baseline, week 2, and week 4. The results of this study indicate that a 4-week regimen of clobetasol propionate spray 0.05% treatment in the morning and calcitriol ointment 3 microg/g in the evening is efficacious and without unexpected safety issues for the management of moderate plaque psoriasis.

Clobetasol propionate 0.05% spray for the management of moderate-to-severe plaque psoriasis of the scalp: results from a randomized controlled trial.

BACKGROUND: Clobetasol propionate 0.05% spray is available for treating moderate-to-severe plaque psoriasis; however, there is limited information with plaque psoriasis of the scalp. OBJECTIVE: Evaluate the efficacy, safety, and quality-of-life impact of clobetasol propionate 0.05% spray in patients with moderate to severe plaque psoriasis of the scalp. METHODS: Multicenter, randomized, double-blind, vehicle-controlled study involving 81 men and women with moderate-to-severe (Global Severity Score [GSS] = 3 or 4) plaque psoriasis of the scalp. Eligible patients were treated with clobetasol propionate 0.05% spray or vehicle spray, which was applied twice daily for up to four weeks. The primary efficacy end point was the GSS of psoriasis of the scalp after four weeks. Safety assessments included local tolerability, presence of Cushing's syndrome, and adverse events. RESULTS: At the end of treatment, 85 percent (35/41) of patients in the clobetasol propionate 0.05% spray group achieved success (GSS clear or almost clear), compared with 13 percent (5/40) in the vehicle spray group (P is less than .001). The proportion of patients treated with clobetasol propionate 0.05% spray who achieved a rating of clear (GSS = 0) after two weeks and at the end of treatment was 12 percent and 51 percent, respectively. Clobetasol propionate 0.05% spray was well tolerated, and there were no serious adverse events or reported cases of folliculitis or Cushing's syndrome. CONCLUSION: Treatment with clobetasol propionate 0.05% spray for up to four weeks is effective and well tolerated for moderate-to-severe plaque psoriasis of the scalp.