BackgroundIntrathecal pseudodelivery is a new route of drug delivery to the CNS based on an implantable device endowed with a smart system of nanoporous membranes. We have developed a miniaturized prototype of the device for rodents. Here we present preliminary results on the use of antiAbeta mAbs intrathecally pseudodelivered in the APP/PS1 mouse model of Alzheimer’s disease.Method28‐week‐old male mice, APP/PS1 and non‐transgenic were used. The device was implanted subcutaneously in the back of the mouse and connected to one of the lateral ventricles via a catheter, also subcutaneous. The reservoir of the devices was filled with artificial CSF (aCSF) or with a solution of anti‐amyloid beta (Ab) antibody (clone 6E10, Biolegend) in aLCR. The infusion period was three weeks, during which animal welfare aspects were assessed. After this time, the mice were sacrificed for histopathological evaluation. All procedures were performed in accordance with institutional guidelines approved by the Ethical Committee in Research of Universidad de Oviedo.Result Safety: The device was successfully implanted in a total of 18 mice. Three mice showed complications 3 days after surgery, including lethargy and significant weight loss. This could be due to the surgery itself or to the post‐operative medication. The rest of the mice recovered perfectly and returned to normal activity 4 days after surgery.Efficacy: Immunohistochemistry was performed to assess the size of Ab plaques, using a rabbit polyclonal anti‐Ab antibody (Invitrogen). The surface area occupied by the plaques in each of the APP/PS1 mice was determined. The results show a decrease in the area occupied by Ab‐positive plaques in the mice treated with the antibody. Although not statistically significant, there is a tendency for treated mice to have a smaller area occupied by plaques.ConclusionsOur results show that:• Intrathecal pseudodelivery of mAbs is a feasible route of drug delivery for neurodegenerative diseases.• Intrathecal pseudodelivery of Ab‐mAb alleviates pathology in an Alzheimer’s disease model.• Albeit preliminary efficacy and safety results are promising, further studies are needed.
ResumenIntroducción. El meningocele sacro anterior es una rara forma de disrafismo espinal, localizado en el espacio presacro extraperitoneal. Generalmente es asintomático y suele presentarse como una pequeña masa pélvica.Caso clínico. Presentamos el caso de un niño de 10 años de edad que desarrolla una meningitis bacteriana consecuencia de un absceso pararectal que se comunica con una cavidad meningocélica sacra anterior. Recibe tratamiento quirúrgico realizándose con éxito un abordaje posterior.Conclusión. La finalidad de la cirugía es reparar el defecto dural y obliterar la comunicación existente entre el saco tecal y el defecto herniario. El abordaje posterior es la técnica quirúrgica más efectiva puesto que tiene menor riesgo de daño neurológico que el abordaje anterior.PALABRAS CLAVE. Meningocele sacro anterior. Masa pélvica. Absceso pararectal. Defecto dural. Occult anterior sacral meningocele SummaryBackground. The anterior sacral meningocele is a rare form of spinal dysraphism located in the presacral extraperitoneal space. It is generally asymptomatic and appears as a small pelvic mass.Case description. We present a case of a 10 year-old male that developes a bacteria meningitis because of a pararectal abscess that is connected with an anterior sacral meningocele. We successfully treated it using a posterior approach.Conclusion. The aim of the surgery is to repair the dural defect and to obliterate the communication between the thecal sac and the herniation defect. The posterior approach is the simplest and most effective surgical technique because the lower risk of neurological injury than the anterior approach.KEY WORDS. Anterior sacral meningocele. Pelvic mass. Pararectal abscess. Dural defect.
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