AAV-mediated expression of HLA-G1/5 reduces severity of experimental autoimmune uveitis

AbstractNon-infectious uveitis (NIU) is an intractable, recurrent, and painful disease that is a common cause of vision loss. Available treatments of NIU, such as the use of topical corticosteroids, are non-specific and have serious side effects which limits them to short-term use; however, NIU requires long-term treatment to prevent vision loss. Therefore, a single dose therapeutic that mediates long-term immunosuppression with minimal side effects is desirable. In order to develop an effective long-term therapy for NIU, an adeno-associated virus (AAV) gene therapy approach was used to exploit a natural immune tolerance mechanism induced by the human leukocyte antigen G (HLA-G). To mimic the prevention of NIU, naïve Lewis rats received a single intravitreal injection of AAV particles harboring codon-optimized cDNAs encoding HLA-G1 and HLA-G5 isoforms one week prior to the induction of experimental autoimmune uveitis (EAU). AAV-mediated expression of the HLA-G-1 and -5 transgenes in the targeted ocular tissues following a single intravitreal injection of AAV-HLA-G1/5 significantly decreased clinical and histopathological inflammation scores compared to untreated EAU eyes (p < 0.04). Thus, localized ocular gene delivery of AAV-HLA-G1/5 may reduce the off-target risks and establish a long-term immunosuppressive effect that would serve as an effective and novel therapeutic strategy for NIU, with the potential for applications to additional ocular immune-mediated diseases.

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Long-term use of anagrelide in young patients with essential thrombocythemia

Blood ◽

10.1182/blood.v97.4.863 ◽

2001 ◽

Vol 97 (4) ◽

pp. 863-866 ◽

Cited By ~ 106

Author(s):

Elizabeth C. Storen ◽

Ayalew Tefferi

Keyword(s):

Side Effects ◽

Essential Thrombocythemia ◽

Young Patients ◽

Drug Efficacy ◽

Initial Response ◽

Drug Dosage ◽

Similar Proportion ◽

Term Therapy ◽

Long Term Treatment

Abstract Anagrelide is a novel platelet-lowering agent that has recently been approved for use in essential thrombocythemia (ET) and related disorders. Short-term drug efficacy and toxicity data have previously been presented. The purpose of this study was to obtain additional information regarding long-term anagrelide use. This is a retrospective series of 35 young patients (17 to 48 years) with ET who received anagrelide treatment before 1992. Initial drug dosage ranged between 1 and 10 mg/d, and the median maintenance dosage was 2.5 mg/d. The overall initial response rate of 94% included 74% complete remissions and 20% partial remissions. Of the 33 responding patients, 27 (82%) remained on anagrelide therapy for a median of 10.8 years (range, 7 to 15.5). Of these, 66% maintained a complete and 34% a partial remission over the study period. In general, the reporting of somatic side effects decreased over time, and anemia was the only new side effect that emerged after long-term therapy. Eight patients (24%) experienced a more than 3 g/dL decrease in hemoglobin level. Despite active therapy, 20% of the patients experienced a total of 10 thrombotic episodes, and a similar proportion experienced major hemorrhagic events. All thrombohemorrhagic complications occurred at a platelet count of more than 400 × 109/L. It is concluded that long-term treatment of ET with anagrelide is associated with decreased reporting of initial side effects and the development of mild-to-moderate anemia. Complete normalization of platelet counts may be needed to minimize residual thrombohemorrhagic risk during therapy.

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Aspects of Long-Term Treatment with Neuroleptics Historical and Literature Review—Personal Experience with Fluspirilene and Penfluridol

Journal of International Medical Research ◽

10.1177/030006057500300210 ◽

1975 ◽

Vol 3 (2) ◽

pp. 114-124 ◽

Cited By ~ 1

Author(s):

Lucian Floru

Keyword(s):

Side Effects ◽

Literature Review ◽

Personal Experience ◽

Term Treatment ◽

Term Therapy ◽

Tabular Form ◽

Long Term Effects ◽

Long Term Treatment ◽

Long Term Therapy

The literature on neuroleptics with substance-specific long-term effects (fluspirilene, penfluridol) is reviewed in tabular form. This is followed by a report of personal investigations on 76 schizophrenics who were treated with fluspirilene initially within the hospital and later on an out-patient basis, on 86 patients who were treated with it exclusively at the out-patients' department, as well as on 123 schizophrenic psychoses treated with penfluridol in the out-patients' department. The side-effects caused by the two substances are compared. Pre-requisites for effective long-term therapy with a few complications are discussed.

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Instant Hydrogelation of Dexamethasone-Peptide Conjugate Attenuates Experimental Autoimmune Uveitis (EAU) Without Causing Apparent Ocular Side-Effects

SSRN Electronic Journal ◽

10.2139/ssrn.3751556 ◽

2019 ◽

Author(s):

Renshu Zhang ◽

Jianhong Zhou ◽

Dan Lin ◽

Yuhan Hu ◽

Bo Jin ◽

...

Keyword(s):

Side Effects ◽

Experimental Autoimmune Uveitis ◽

Autoimmune Uveitis ◽

Ocular Side ◽

Experimental Autoimmune

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Slow-Release Terbutaline and Theophylline for the Long-Term Therapy of Children With Asthma: A Latin Square and Factorial Study of Drug Effects and Interactions

PEDIATRICS ◽

10.1542/peds.84.1.119 ◽

1989 ◽

Vol 84 (1) ◽

pp. 119-125

Author(s):

Olivia Kit Wun Chow ◽

Kam Pui Fung

Keyword(s):

Side Effects ◽

Slow Release ◽

Clinical Symptoms ◽

Combined Therapy ◽

Latin Square ◽

Term Therapy ◽

Long Term Effects ◽

Long Term Treatment ◽

Children With Asthma

To evaluate the long-term effects of slow-release formulations of theophylline and terbutaline on pulmonary function, clinical symptoms, and side effects, 24 children with stable and moderately severe perennial asthma participated in a prospective double-blind crossover study. The patients and the treatments were randomized according to the Latin square design to eliminate all possible period/climate biases throughout the protracted study period. The treatments consisted of terbutaline, 5 mg, theophylline, 200 mg, the combination, and placebo, given twice daily orally and crossing over every 28 days. The two drugs, administered alone or in combination, improved lung function and symptoms when compared with placebo. The interaction of theophylline and terbutaline was quantitatively shown by 2 x 2 factorial statistical design to be essentially additive rather than synergistic in the control of asthma. No increase in side effects was noted when the combined therapy was used. These findings suggest therapeutic advantages to combining submaximal oral doses of sustained-release theophylline and terbutaline for the long-term treatment of children with asthma.

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