Dinutuximab (Ch14.18, tradename Unituxin) and dinutuximab beta (tradename Qarziba) are monoclonal antibodies used as a second-line treatment for children with high-risk neuroblastoma. Each antibody is made of both mouse and human components and targets glycolipid GD2, expressed on neuroblastoma cells and on normal cells of neuroectodermal origin, including the central nervous system and peripheral nerves. They differ in that dinutuximab is manufactured using mouse cells, and dinutuximab beta is manufactured using hamster cells. The dosing regime differs, and dinutuximab is given in combination with granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-2 (IL-2) and 13-cis-retinoic acid (RA), while dinutuximab beta can be given alone. They both cause severe side effects, including severe pain that must be controlled with morphine, and a high risk of infusion reaction that must be controlled with antihistamines and anti-inflammatory drugs. They both work by binding to neurons and causing the bodys immune system to destroy them. Dinutuximab received marketing approval in the US and in the European Union in March 2015; the marketing approval was withdrawn in 2017. Dinutuximab beta received marketing approval in Europe in 2017. The antibody was originally called Ch14.18 and was discovered by a group at University of California San Diego led by Alice Yu; this antibody and several others were brought into clinical trials funded by the National Cancer Institute. Medical use
Dinutuximab is used as post-consolidation therapy for children with high-risk neuroblastoma, in combination with granulocyte-macrophage colony-stimulating factor, interleukin-2, 13-cis-retinoic acid.
These prions then form clusters in the brain, which are responsible for the neurodegenerative effects seen in patients.The P102L mutation, which causes a substitution of proline to a leucine in codon 102, has been found in the prion protein gene (PRNP, on chromosome 20) of most affected individuals. Therefore, it appears this genetic change is usually required for the development of the disease. Diagnosis
GSS can be identified through genetic testing. Testing for GSS involves a blood and DNA examination in order to attempt to detect the mutated gene at certain codons. If the genetic mutation is present, the patient will eventually develop GSS. Treatment
There is no cure for GSS, nor is there any known treatment to slow the progression of the disease. Therapies and medication are aimed at treating or slowing down the effects of the symptoms. The goal of these treatments is to try to improve the patients quality of life as much as possible. There is some ongoing research to find a cure, with one of the most prominent examples being the PRN100 monoclonal antibody. Prognosis
GSS is a disease that progresses slowly, lasting roughly 2–10 years, with an average of approximately five years. The disease ultimately results in death, most commonly from the patient either going into a coma, or from a secondary infection due to the patients loss of bodily functions. Research
Prion diseases, also called transmissible spongiform encephalopathies (TSEs), are neurodegenerative diseases of the brain thought to be caused by a protein that converts to an abnormal form called a prion.