Carriers of ataxia-telangiectasia gene display additional protein fraction and changes in the environment of SH groups in erythrocyte membrane

Rybczyńska, Maria; Pawlak, A.L.; Hoffmann, S. K.; Ignatowicz, R

doi:10.1016/0005-2736(90)90272-p

Cited by 5 publications

(1 citation statement)

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“…One finding that needs further exploration is the low level of DSP-erythrocyte encapsulation (almost half of the patients had mean infusion bag doses of less than 5 mg of DSP) and high level of variability in this trial, in comparison to previous studies that used EryDex as treatment device [20-25]. This may be due to an intrinsic biochemical change in the cell membrane of the erythrocyte in AT patients, as previously reported [26,27]. These changes in physico-chemical properties could influence the encapsulation of DSP into AT patients’ erythrocytes and the consequent release of the active drug into the circulation.…”

Section: Discussionmentioning

confidence: 55%

Intra-Erythrocyte Infusion of Dexamethasone Reduces Neurological Symptoms in Ataxia Teleangiectasia Patients: Results of a Phase 2 Trial

Chessa

Leuzzi

Plebani

et al. 2014

Orphanet J Rare Dis

122

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BackgroundAtaxia Teleangiectasia [AT] is a rare neurodegenerative disease characterized by early onset ataxia, oculocutaneous teleangiectasias, immunodeficiency, recurrent infections, radiosensitivity and proneness to cancer. No therapies are available for this devastating disease. Recent observational studies in few patients showed beneficial effects of short term treatment with betamethasone. To avoid the characteristic side effects of long-term administration of steroids we developed a method for encapsulation of dexamethasone sodium phosphate (DSP) into autologous erythrocytes (EryDex) allowing slow release of dexamethasone for up to one month after dosing. Aims of the study were: the assessment of the effect of EryDex in improving neurological symptoms and adaptive behaviour of AT patients; the safety and tolerability of the therapy.MethodsTwenty two patients (F:M = 1; mean age 11.2 ± 3.5) with a confirmed diagnosis of AT and a preserved or partially supported gait were enrolled for the study. The subjects underwent for six months a monthly infusion of EryDex. Ataxia was assessed by the International Cooperative Ataxia Rating Scale (ICARS) and the adaptive behavior by Vineland Adaptive Behavior Scales (VABS). Clinical evaluations were performed at baseline and 1, 3, and 6 months.ResultsAn improvement in ICARS (reduction of the score) was detected in the intention-to-treat (ITT) population (n = 22; p = 0.02) as well as in patients completing the study (per protocol PP) (n = 18; p = 0.01), with a mean reduction of 4 points (ITT) or 5.2 points (PP). When compared to baseline, a significant improvement were also found in VABS (increase of the score) (p < 0.0001, ITT, RMANOVA), with statistically significant increases at 3 and 6 months (p < 0.0001). A large inter-patient variability in the incorporation of DSP into erythrocytes was observed, with an evident positive effect of higher infusion dose on ICARS score decline. Moreover a more marked improvement was found in less neurologically impaired patients. Finally, a 19 month-extension study involving a subgroup of patients suggested that Erydex treatment can possibly delay the natural progression of the disease.EryDex was well tolerated; the most frequent side effects were common AT pathologies.ConclusionsEryDex treatment led to a significant improvement in neurological symptoms, without association with the typical steroid side effects.Trial registrationCurrent Controlled Trial 2010-022315-19SpA

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Section: Discussionmentioning

confidence: 55%