GeneticMedicinesIII-Feb7(s) (1) - Copy Flashcards
(54 cards)
What is Leber congenital amaurosis (LCA)?
One of the most common causes of blindness in children (1:40,000)
LCA is associated with mutations in the RPE65 gene, particularly type 2.
What gene mutation is associated with Leber congenital amaurosis?
Mutation in RPE65
RPE65 produces retinal pigment epithelial-specific protein necessary for vision.
What are the results of RPE65 mutations?
Dysfunction and degeneration of retina
This results in vision impairment.
What was the vector used in the initial clinical trials for LCA?
AAV2-RPE65 vector
This vector was injected sub-retinally.
When were the initial clinical trials for LCA conducted?
2008
The trials showed visual function improvement in all treated patients.
What improvements were observed in the study eyes during LCA trials?
Cone and rod sensitivities increased significantly
Improvements were localized to treated areas.
When was the first gene therapy for LCA approved?
October 2020
Patients must still have viable retinal cells for treatment.
What is familial lipoprotein lipase deficiency?
An autosomal-recessive disorder caused by LPL mutation
It leads to hypertriglyceridemia and related health issues.
What are the consequences of LPL mutation?
Hypertriglyceridemia, jaundice, recurrent pancreatitis, enlarged liver, cutaneous xanthomata
These conditions result from the dysfunction of fat metabolism.
What is Glybera?
Muscle-specific AAV1-LPL gene therapy
It costs ~$1 million per treatment.
What was the outcome of Glybera treatment?
40% reduction in median fasting plasma TG between 3-12 weeks
The reduction rebounded by week 26.
What disorder is associated with mutations in the factor IX gene?
Hemophilia B
Hemophilia B is an X-linked recessive disorder affecting males.
What mutation causes Hemophilia A?
Mutation in F8 gene
Hemophilia A is also an X-linked recessive disorder.
How are factor levels affected in hemophilia disorders?
Usually less than 1% of normal factor levels
This leads to increased bleeding risk.
What is Hemophilia B?
A genetic disorder caused by a deficiency of factor IX
What vector is used in the treatment of Hemophilia B?
Self-complementary adeno-associated virus (AAV) vector expressing a human factor IX transgene (scAAV2/8-LP1-hFIXco)
What was the increase in factor IX levels after treatment with scAAV2/8-LP1-hFIXco?
3-11% up to 16 months after treatment
What is the significance of the factor IX variant discovered in Hemophilia B?
It is a hyperactive FIX gene associated with thrombophilia
What is HEMGENIX and when was it approved?
A treatment for Hemophilia B, FDA approved in Nov 2022
What is the average level of factor IX achieved with HEMGENIX?
33% FIX levels
What is Roctavian and when was it approved?
A treatment for Hemophilia B, EU approved in July 2022 and FDA approved in July 2023
What is Spinal Muscular Atrophy type I?
A genetic disorder characterized by the loss of motor neurons leading to muscle weakness
What gene is targeted by Zolgensma for treating Spinal Muscular Atrophy?
SMN1 gene
What is the cost of Zolgensma?
~$2.1 million
