Diagnosis
Blood tests may show anaemia and their lipid profiles are generally similar to people with more common familial hypercholesterolemia, including elevated total cholesterol, elevated low-density lipoprotein cholesterol, decreased high-density lipoprotein cholesterol and elevated serum transaminases.Liver biopsy findings will generally show a bright yellow-orange color, enlarged, lipid-laden hepatocytes and Kupffer cells, microvesicular and macrovesicular steatosis, fibrosis, and cirrhosis. The only definitive tests are genetic, which may be conducted in any number of ways. Screening
Because LAL deficiency is inherited, each sibling of an affected individual has a 25% chance of having pathological mutations in LAL genes from both their mother and their father, a 50% chance of having a pathological mutation in only one gene, and a 25% chance of having no pathological mutations. Genetic testing for family members and genetic prenatal diagnosis of pregnancies for women who are at increased risk are possible if family members carrying pathological mutations have been identified. Management
LAL deficiency can be treated with sebelipase alfa is a recombinant form of LAL that was approved in 2015 in the US and EU. The disease of LAL affects < 0.2 in 10,000 people in the EU. According to an estimate by a Barclays analyst, the drug will be priced at about US$375,000 per year.It is administered once a week via intraveneous infusion in people with rapidly progressing disease in the first six months of life.
Patisiran, sold under the brand name Onpattro, is a medication used for the treatment of polyneuropathy in people with hereditary transthyretin-mediated amyloidosis, a fatal rare disease that is estimated to affect 50,000 people worldwide.It is the first small interfering RNA-based drug approved by the U.S. Food and Drug Administration (FDA) and the first drug approved by the FDA to treat this condition. It is a gene silencing drug that interferes with the production of an abnormal form of transthyretin. Patisiran utilizes a novel approach to target and reduce production of the TTR protein in the liver via the RNAi pathway.Patisiran was developed and is marketed by Alnylam. The FDA considers it to be a first-in-class medication. History
Patisiran was granted orphan drug status, fast track designation, priority review and breakthrough therapy designation due to its novel mechanism and the rarity of the condition it treats. It was approved for medical use in the United States and in the European Union in August 2018. The per-patient cost is between US$451,430 and US$677,145 per year, depending on the number of vials needed. Formulation
The siRNA active component of Patisiran is formulated into lipid nanoparticles, which protect the RNA and facilitate its delivery to target tissues. The lipid nanoparticle formulation includes buffer components, as well as the lipid components DLin-MC3-DMA, Distearoylphosphatidylcholine, cholesterol, and the PEGylated lipid DMG-PEG 2000. Society and culture
Economics
As of 2020, there were 1050 people globally receiving patisiran, generating $65.5M in net-revenues for Alnylam Pharmaceuticals. References
External links
"Patisiran". Drug Information Portal. U.S. National Library of Medicine.