Hypophosphatasia (; also called deficiency of alkaline phosphatase, phosphoethanolaminuria, or Rathbuns syndrome; sometimes abbreviated HPP) is a rare, and sometimes fatal, inherited metabolic bone disease. Clinical symptoms are heterogeneous, ranging from the rapidly fatal, perinatal variant, with profound skeletal hypomineralization, respiratory compromise or vitamin B6 dependent seizures to a milder, progressive osteomalacia later in life. Tissue non-specific alkaline phosphatase (TNSALP) deficiency in osteoblasts and chondrocytes impairs bone mineralization, leading to rickets or osteomalacia. The pathognomonic finding is subnormal serum activity of the TNSALP enzyme, which is caused by one of 388 genetic mutations identified to date, in the gene encoding TNSALP. Genetic inheritance is autosomal recessive for the perinatal and infantile forms but either autosomal recessive or autosomal dominant in the milder forms. The prevalence of hypophosphatasia is not known; one study estimated the live birth incidence of severe forms to be 1:100,000. and some studies report a higher prevalence of milder disease. Symptoms and signs
There is a remarkable variety of symptoms that depends, largely, on the age of the patient at initial presentation, ranging from death in utero to relatively mild bone problems with or without dentition symptoms in adult life although neurological and extra-skeletal symptoms are also reported. The stages of this disease are generally included in the following categories: perinatal, infantile, childhood, adult, benign prenatal and odontohypophosphatasia.
Bamlanivimab is a monoclonal antibody developed by AbCellera Biologics and Eli Lilly as a treatment for COVID-19. The medication was granted an emergency use authorization (EUA) by the US Food and Drug Administration (FDA) in November 2020, and the EUA was revoked in April 2021.Bamlanivimab is an IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2. The aim is to block viral attachment and entry into human cells, thus neutralizing the virus, and help preventing and treating COVID-19.Bamlanivimab emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19.Bamlanivimab is also used as part of the bamlanivimab/etesevimab combination that was granted an EUA by the FDA.In June 2021, the US Office of the Assistant Secretary for Preparedness and Response (ASPR) paused distribution of bamlanivimab and etesevimab together, and etesevimab alone (to pair with existing supply of bamlanivimab), due to the increase of circulating variants. Studies
Bamlanivimab has been studied in several trials. Some initial results on bamlanivimab seemed promising, with one review saying that it "decrease[s] viral load when given early on in the course of SARS-CoV-2 infection and favourably impact[s] clinical outcomes for patients with mild-to-moderate COVID-19". However, further results have not shown any clinically relevant benefit. Animal trials
An initial trial tested bamlanivimab in rhesus monkeys. Administration of the drug reduced SARS-CoV-2 replications in the upper and lower respiratory tract of monkeys.Following these results in a non-human primate model, several human studies were initiated.