Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy.

BACKGROUND: In X-linked adrenoleukodystrophy, mutations in ABCD1 lead to loss of function of the ALD protein. Cerebral adrenoleukodystrophy is characterized by demyelination and neurodegeneration. Disease progression, which leads to loss of neurologic function and death, can be halted only with allogeneic hematopoietic stem-cell transplantation. METHODS: We enrolled boys with cerebral adrenoleukodystrophy in a single-group, open-label, phase 2-3 safety and efficacy study. Patients were required to have early-stage disease and gadolinium enhancement on magnetic resonance imaging (MRI) at screening. The investigational therapy involved infusion of autologous CD34+ cells transduced with the elivaldogene tavalentivec (Lenti-D) lentiviral vector. In this interim analysis, patients were assessed for the occurrence of graft-versus-host disease, death, and major functional disabilities, as well as changes in neurologic function and in the extent of lesions on MRI. The primary end point was being alive and having no major functional disability at 24 months after infusion. RESULTS: A total of 17 boys received Lenti-D gene therapy. At the time of the interim analysis, the median follow-up was 29.4 months (range, 21.6 to 42.0). All the patients had gene-marked cells after engraftment, with no evidence of preferential integration near known oncogenes or clonal outgrowth. Measurable ALD protein was observed in all the patients. No treatment-related death or graft-versus-host disease had been reported; 15 of the 17 patients (88%) were alive and free of major functional disability, with minimal clinical symptoms. One patient, who had had rapid neurologic deterioration, had died from disease progression. Another patient, who had had evidence of disease progression on MRI, had withdrawn from the study to undergo allogeneic stem-cell transplantation and later died from transplantation-related complications. CONCLUSIONS: Early results of this study suggest that Lenti-D gene therapy may be a safe and effective alternative to allogeneic stem-cell transplantation in boys with early-stage cerebral adrenoleukodystrophy. Additional follow-up is needed to fully assess the duration of response and long-term safety

Study Group)

Objective: In this study, it was aimed to evaluate the relationship between vitamin D level and pain severity, localization and duration in patients with non-specific musculoskeletal pain.Materials and Methods: Patients who applied to physical medicine and rehabilitation outpatient clinics due to non-specific muscle pain in 19 centers in Turkey were retrospectively screened. Three thousand four hundred fourpatients were included in the study, whose pain level was determined by visual analog scale (VAS) and the painful region, duration of pain and vitamin D level were reached. D group was found to be D deficient (group 1) when 25 (OH) D level was 20 ng/mL or less and group D 2 (vitamin D deficiency) was higher than 30 ng/mL (group 3). The groups were compared in terms of pain duration, localization and severity. In addition, the correlations of pain localization, severity and duration with vitamin D levels were examined.Results: D vitamin deficiency was detected in 2202 (70.9%) of 3 thousand four hundred and four registered patients, and it was found that vitamin D deficiency in 516 (16.6%) and normal vitamin D in 386 (12.4%). The groups were similar in terms of age, body mass index, income level, duration of complaint, education level, family type and working status (p>0.05). There was no statistically significant difference between groups in terms of VAS, pain localization and duration scores (p>0.05).Conclusion: Our study shows that vitamin D deficiency in patients with nonspecific musculoskeletal pain is not associated with the severity and duration of pain