Publications by authors named "Sara Haghighi"

11 Publications

  • Page 1 of 1

Open-label study with the monoamine stabilizer (-)-OSU6162 in myalgic encephalomyelitis/chronic fatigue syndrome.

Brain Behav 2021 Apr 2;11(4):e02040. Epub 2021 Feb 2.

Gottfries Clinic, Affiliated with Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Objectives: The purpose of the present study was to investigate the safety and tolerability of the monoaminergic stabilizer (-)-OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In addition, a potential therapeutic effect of (-)-OSU6162 in ME/CFS was evaluated by means of observer-rated scales and self-assessment rating scales.

Materials And Methods: In the current study using an open-label single-arm design ME/CFS patient received treatment with (-)-OSU6162 during 12 weeks. The patients received the following doses of (-)-OSU6162: 15 mg b.i.d. during the first 4-week period, up to 30 mg b.i.d. during the second 4-week period and up to 45 mg b.i.d. during the third 4-week period, with follow-up visits after 16 and 20 weeks.

Results: Out of 33 included patients, 28 completed the 12 weeks treatment period. (-)-OSU6162 was well tolerated; only one patient discontinued due to an adverse event. Vital signs and physical examinations showed no abnormal changes. Blood analyses showed an increase in serum prolactin. Therapeutically, improvements were seen on the Clinical Global Impression of Change scale, the FibroFatigue scale, the Mental Fatigue Scale, the Fatigue Severity Scale, Beck Depression Inventory, and the Short Form 36 Health Survey Questionnaire.

Conclusions: (-)-OSU6162 is well tolerated in ME/CFS patients and shows promise as a novel treatment to mitigate fatigue and improve mood and health-related quality of life in ME/CFS. Obviously, the present results need to be confirmed in future placebo-controlled double-blind trials.
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http://dx.doi.org/10.1002/brb3.2040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035472PMC
April 2021

RebiQoL: A randomized trial of telemedicine patient support program for health-related quality of life and adherence in people with MS treated with Rebif.

PLoS One 2019 5;14(7):e0218453. Epub 2019 Jul 5.

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

RebiQoL was a phase IV multicenter randomized study to assess the impact of a telemedicine patient support program (MSP) on health-related quality of life (HRQoL) in patients with relapsing-remitting MS (RRMS) being administered with Rebif with the RebiSmart device. The primary endpoint was to assess the impact of MSP compared to patients only receiving technical support for RebiSmart on HRQoL at 12 months, using the psychological part of Multiple Sclerosis Impact Scale (MSIS-29), in patients administered with Rebif. A total of 97 patients diagnosed with RRMS were screened for participation in the study of which 3 patients did not fulfill the eligibility criteria and 1 patient withdrew consent. Of the 93 randomized patients, 46 were randomized to MSP and 47 to Technical support only. The demographic characteristics of the patients were well-balanced in the two arms. There were no statistical differences (linear mixed model) in any of the primary (difference of 0.48, 95% CI: -8.30-9.25, p = 0.91) or secondary outcomes (p>0.05). Although the study was slightly underpowered, there was a trend towards better adherence in the MSP group (OR 3.5, 95% CI 0.85-14.40, p = 0.08) although not statistically significant. No unexpected adverse events occurred. This study did not show a statistically significant effect of the particular form of teleintervention used in this study on HRQoL as compared to pure technical support, for MS patients already receiving Rebif with the RebiSmart device. Trial Registration: ClinicalTrials.gov: NCT01791244.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218453PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611587PMC
February 2020

Open study with (-)-OSU6162 in multiple sclerosis-related fatigue.

Acta Neurol Scand 2018 Dec 22;138(6):482-489. Epub 2018 Aug 22.

Gottfries Clinic, affiliated with Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Objectives: The main objective of this study was to investigate the tolerability and safety of the monoaminergic stabilizer (-)-OSU6162 in patients with multiple sclerosis (MS). In addition, a potential therapeutic effect of (-)-OSU6162 with focus on MS-related fatigue was estimated by means of various self-assessment rating scales as well as a clinical investigator-rated scale.

Materials And Methods: In this open-label, single-arm study, 30 MS patients received treatment with the monoaminergic stabilizer (-)-OSU6162 during 12 weeks. The dose of (-)-OSU6162 was 15 mg twice daily during the first 4-week period, up to 30 mg twice daily during the second 4-week period and up to 45 mg twice daily during the third 4-week period, with follow-up visits after 16 and 20 weeks. MS-related fatigue was rated by the clinical investigator or by self-assessments, using mainly established rating scales. Twenty-five patients completed the study.

Results: (-)-OSU6162 was well tolerated by all patients, and no serious adverse events were observed. Therapeutically, improvements were observed with respect to fatigue and mood, as judged by ratings on the Mental Fatigue Scale (MFS), Short Form-36 (SF-36) scale and Beck Depression Inventory (BDI). Furthermore, the large majority of patients were rated as globally improved in the medical observers' rating scale Clinical Global Impression of Change (CGI-C).

Conclusions: In view of its good tolerability, (-)-OSU6162 may offer a new treatment option for alleviating mental fatigue, as well as depression, in MS. Larger, randomized double-blind controlled trials are warranted to confirm the present preliminary observations.
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http://dx.doi.org/10.1111/ane.13007DOI Listing
December 2018

Tolerability and efficacy of the monoaminergic stabilizer (-)-OSU6162 (PNU-96391A) in Huntington's disease: a double-blind cross-over study.

Acta Neuropsychiatr 2014 Oct;26(5):298-306

5Department of Neurology,Sahlgrenska University Hospital,Gothenburg/Skaraborg Hospital,Skövde,Sweden.

Objective: To evaluate the safety (primary objective) and efficacy (secondary objective) of (-)-OSU6162 in Huntington's disease (HD).

Methods: In a double-blind, cross-over trial, patients with HD were randomly assigned to start treatment on either (-)-OSU6162 or placebo. After 4 weeks, those patients who initially received active drug were switched to placebo for another 4 weeks, and vice versa. During the first week the (-)-OSU6162 dose was 15 mg twice daily, during the second week 30 mg twice daily, and during the last 2 weeks 45 mg twice daily. Motor, cognitive, mental and social functions were rated by the clinical investigator or by self-assessment, using established rating scales.

Results: Fifteen patients fulfilling inclusion and exclusion criteria completed the study. (-)-OSU6162 was well tolerated by all patients and no adverse effects were observed. (-)-OSU6162 treatment significantly improved the Short Form 36 Vitality score, mainly due to an improvement of the individual item 'worn-out' (VT3). In addition, an improvement of depressive symptoms was found using Beck Depression Inventory. In contrast to a general trend of improvement in several non-motor variables only small and non-significant differences between (-)-OSU6162 and placebo were found regarding motor functions.

Conclusions: (-)-OSU6162 offers promise for the treatment of HD, as a drug with good tolerability, capable of improving the patients' experienced non-motor functions such as energy and mood and thus alleviating symptoms of great importance for their quality of life.
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http://dx.doi.org/10.1017/neu.2014.16DOI Listing
October 2014

The effect of live, attenuated measles vaccine and measles infection on measles antibody levels in serum and CSF of patients with multiple sclerosis or clinically isolated syndrome.

J Neuroimmunol 2011 Jun 7;235(1-2):98-103. Epub 2011 May 7.

Institute of Neuroscience and Physiology, Department of Neurology, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden.

High occurrence of measles, rubella and varicella zoster antibodies has been used as a biomarker for MS (the MRZ test). We analyzed measles antibody titres with respect to measles infection/measles vaccination status in 166 patients with MS or clinically isolated syndrome. Fifty blood donors served as controls. Measles vaccination yielded CSF measles antibodies in fewer patients (62%) than measles infection did (87%, p=0.001) and yielded lower measles titres in both serum and CSF (p<0.001). Controls had lower CSF measles titres than patients with measles vaccination alone (p<0.001). Childhood vaccinations probably reduce the sensitivity of the MRZ diagnostic test for MS.
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http://dx.doi.org/10.1016/j.jneuroim.2011.04.002DOI Listing
June 2011

Efficacy and safety of the dopaminergic stabilizer Pridopidine (ACR16) in patients with Huntington's disease.

Clin Neuropharmacol 2010 Sep-Oct;33(5):260-4

Prima Psychiatry, Danderyd Hospital, Stockholm, Sweden.

Objectives: To evaluate the efficacy and safety of the dopaminergic stabilizer pridopidine (ACR16) in patients with Huntington's disease (HD).

Methods: In a randomized, double-blind, placebo-controlled, 4-week trial, patients with HD received pridopidine (50 mg/d, n = 28) or placebo (n = 30). The primary outcome measure was the change from baseline in weighted cognitive score, assessed by cognitive tests (Symbol Digit Modalities, verbal fluency, and Stroop tests). Secondary outcome measures included changes in the Unified Huntington's Disease Rating Scale, Hospital Anxiety and Depression Scale, Leeds Sleep Evaluation Questionnaire, Reitan Trail-Making Test A, and Clinical Global Impression of Change. Safety assessments were also performed.

Results: There was no significant difference between pridopidine and placebo in the change from baseline of the weighted cognitive score. However, secondary measures such as affective symptoms showed trends toward improvement, and there was significant improvement in voluntary motor symptoms compared with placebo (P < 0.05). Pridopidine was well tolerated, with a safety profile similar to placebo.

Conclusions: Pridopidine shows promise as a treatment for some of the symptoms of HD. In this small-scale study, the most notable effect was improvement in voluntary motor symptoms. Larger, longer-term trials are warranted.
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http://dx.doi.org/10.1097/WNF.0b013e3181ebb285DOI Listing
January 2011

Converging pathways of chromogranin and amyloid metabolism in the brain.

J Alzheimers Dis 2010 ;20(4):1039-49

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Gothenburg and Mölndal, Sweden.

Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (AbetaPP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic AbetaPP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of AbetaPP-derived molecules in cerebrospinal fluid (CSF) with chromogranin (Cg) derived peptides, representing the regulated secretion. Patients with Alzheimer's disease (AD, N=32), multiple sclerosis (MS, N=50), and healthy controls (N= 70) were enrolled. CSF was analyzed for the amyloid peptides Abeta1-42, Abetax-42, Abetax-40, Abetax-38, alpha-cleaved soluble AbetaPP (sAbetaPPalpha), beta-cleaved soluble AbetaPP (sAbetaPPbeta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes AbetaPP into Abeta, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. CSF Cg levels correlated to sAbetaPP and Abeta peptides in AD, MS, and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. These results suggest that a large part of AbetaPP in the human central nervous system is processed in the regulated secretory pathway of neurons.
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http://dx.doi.org/10.3233/JAD-2010-091651DOI Listing
October 2010

Relapses in multiple sclerosis are associated with increased CD8+ T-cell mediated cytotoxicity in CSF.

J Neuroimmunol 2008 May 8;196(1-2):159-65. Epub 2008 Apr 8.

Sahlgrenska Academy, Department of Neurology, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.

MS is thought to be mediated by CD4(+) T-helper cells. To investigate the importance of CD8(+) cytotoxic T-cells in MS we analyzed peripheral blood T-cells by DNA microarray, and plasma and CSF levels of granzymes from MS patients and controls. Cytotoxic gene expression was decreased in peripheral T-cells from RRMS patients whereas plasma levels of granzymes were unchanged. However, granzyme levels were elevated in the CSF of RRMS patients at relapse compared with controls and remission. Thus, CD8+ T-cell-mediated cytotoxicity is confined to the CSF/CNS compartment in RRMS patients and may be involved in the immunopathogenesis of clinical relapses.
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http://dx.doi.org/10.1016/j.jneuroim.2008.03.001DOI Listing
May 2008

Cerebrospinal fluid concentrations of peptides derived from chromogranin B and secretogranin II are decreased in multiple sclerosis.

J Neurochem 2007 Dec 22;103(5):1932-9. Epub 2007 Oct 22.

Department of Neurochemistry and Psychiatry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden.

Novel biomarkers for multiple sclerosis (MS) could improve diagnosis and provide clues to pathogenesis. In this study surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to analyze protein expression in CSF from 46 MS patients, 46 healthy siblings to the patients, and 50 unrelated healthy controls. Twenty-four proteins in the mass range 2-10 kDa were expressed at significantly different levels (p < 0.01) in a robust manner when comparing the three groups. Identities of three proteins were determined using biochemical purification followed by tandem mass spectrometric analysis. Immunoprecipitation experiments confirmed the identities for two peptides derived from chromogranin B (m/z 6252) and from secretogranin II (m/z 3679). These peptides were all decreased in MS when compared with siblings or controls. Radioimmunoassays specific for each peptide confirmed these differences. The lowered concentrations did not correlate to the axonal damage marker neurofilament light protein and may thus reflect functional changes rather than neurodegeneration. Further studies will investigate the involvement of these peptides in MS pathogenesis.
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http://dx.doi.org/10.1111/j.1471-4159.2007.04985.xDOI Listing
December 2007

Elevated cerebrospinal fluid F2-isoprostane levels indicating oxidative stress in healthy siblings of multiple sclerosis patients.

Neurosci Lett 2007 Mar 30;414(3):233-6. Epub 2006 Dec 30.

Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgren's University Hospital, S-431 80 Mölndal, Sweden.

Lipid peroxidation has been implicated in the pathogenesis of multiple sclerosis (MS). Isoprostanes, isomers of prostaglandins, are produced by free radical-mediated peroxidation of fatty acids in vivo and can be quantified in biological fluids. This study examines the levels of cerebrospinal fluid (CSF) F2-isoprostanes (F2-iPs) in MS patients (n=46), their healthy siblings (n=46) and unrelated controls (n=50). The median CSF F2-iP concentration (range) was significantly higher in siblings of MS patients, as compared to healthy controls (40.0 [7.1-68.7] and 29.1 [6.4-60.3] pg/mL, respectively, p=0.031). MS patients demonstrated F2-iP levels intermediate between siblings and controls. F2-iP levels in MS patients and siblings correlated significantly (R=0.360, p=0.012). These results suggest that siblings of MS patients have an increased oxidative stress response to environmental and/or genetic factors that may be involved in MS pathogenesis.
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http://dx.doi.org/10.1016/j.neulet.2006.12.044DOI Listing
March 2007

Cystatin C in cerebrospinal fluid and multiple sclerosis.

Ann Neurol 2007 Aug;62(2):193-6; discussion 205

Department of Clinical Neuroscience, University of Göteborg, Sahlgrenska University Hospital/Mölndal, Mölndal, Sweden.

Objective: A recent study using surface-enhanced laser desorption/ionization time-of-flight analysis of cerebrospinal fluid identified a 12.5 kDa truncated isoform of cystatin C (CysC) as a specific biomarker for multiple sclerosis (MS).

Methods: Surface-enhanced laser desorption/ionization time-of-flight analysis of cerebrospinal fluid samples from 43 MS patients and 46 healthy control subjects.

Results: Full-length CysC (13.4 kDa) concentration was similar in MS and control samples. The 12.5 kDa CysC protein was produced from full-length CysC by N-terminal cleavage during storage at -20 degrees C.

Interpretation: The 12.5 kDa CysC isoform is a storage-related artifact and is not useful as a diagnostic marker for MS.
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http://dx.doi.org/10.1002/ana.20945DOI Listing
August 2007