Treatments of Genetic Disease Flashcards
Substrate modulation strategies:
Dietary restrictions
Toxin removal
Metabolic manipulation
Dietary restriction is when you restrict consumption of the offending ____. Examples of disease targets:
Substrate
PKU
organic acidemias
Carbohydrate disease
Fatty acid oxidation disease
PKU is a disease that affects the enzyme that metabolizes _____. Patients should follow a ____ restricted diet and eat protein sources without high amounts of ____, such as vegetables, fruit, special formula, or special breads
Phenylalanine
Phenylalanine
Phenylalanine
Toxin removal facilitates ____ or ___ of toxic substrate. Example is the urea cycle disorders. ____ ____ drugs such as IV Ammonul- benzoate and phenylacetate is used for treatment.
Degradation
Removal
Ammonia-scavenging
Metabolic manipulation is used for ___ ____. Patients have a mutation in the peroxisomal transporter ____, resulting in accumulation of very long chain fatty acids (_____). Treatment is Metabolic rerouting approach using _____. ____ increases SCD1 expression.
X-linked Adrenoleukodystrophy
ABCD1
VLCFA
SCD1 (stearoyal-CoA desaturase-1)
Chloroquine
Substrate reduction therapy blocks a ___ ___ in order to reduce the build up of molecule. _____ is used to reduce the substrate.
Normal enzyme
Eligustat
Advantages and disadvantages of dietary restriction:
Advantages and disadvantages of toxin removal:
Advantages and disadvantage of substrate reduction therapy:
Product supplementation is mostly dietary supplements that provide ___ ____ directly or act as ____ to prevent toxic accumulations. Examples:
Missing compounds
Alternates
Biotin
Pyridoxal phosphate
Betaine for homocystinuria
Dojolvi
Cofactor replacement or supplement ____ endogenous activity. It is mostly oral administration. Examples:
Enhances
Tetrahydrobiopterin (BH4) used in PKU
Palynziq is a substitute for the deficient PAH
Protein replacement therapy is used to treat ____. Clotting factor VII and clotting factor IX are given to patients. Complications: patients can develop ___ and attack the clotting factors, damage to joints and muscles
Hemophilia
Antibodies
Enzyme replacement therapy provides ____ treatment and they cannot cross the blood brain barrier.
____ (donor) blood stem cell transplants can be used to treat neurologic disease.
___ ___ is a correction of patients own cells.
Lifelong
Allogeneic
Gene therapy
Examples of enzyme replacement therapy medications:
____ therapy helps the protein fold into the functional orientation, can improve function slightly. Examples are ___ ___ proteins which are natural cellular chaperones. ____ for Fabry disease and ____ for Gaucher disease.
Chaperone
Heat shock
Galafold
Ambroxol
Cystic fibrosis transmembrane regulator gene (CFTR) is ____ which regulates the flow of ____ ions across the cell membrane. CFT Modulators as treatment:
Mutated
Chlorine
____ is used for sickle cell disease. It increases the amount of fetal hemoglobin. It is ___ ___/___ ___
Hydroxyurea
Protein replacement/metabolic manipulation
Advantages and disadvantages of enzyme replacement therapy:
Advantages and disadvantages of chaperone therapy:
Gene modification therapies:
1.
2.
Antisense oligonucleotides (ASOs)
Small interfering RNA (siRNA)
Anti sense oligonucleotides (ASO) are short ___, single stranded ___. They are used in ___ ___ ____ and ___ ___ ___. Oligonucleotides do not readily cross the __ __ __ and therefor require invasive delivery methods such as ____ or ____ routes
Synthetic
RNA
Duchenne muscular dystrophy
Spinal muscular atrophy
Blood brain barrier
Intrathecal
Intraventricular
ASO methods:
Target degradation and blocking the binding of RNA binding ____ gene expression.
Inhibits
ASO methods:
Helps in exon skipping or inclusion and increases the amount of protein translated from a downstream ORF both ___ gene expression.
Increase
Spinal muscular atrophy (SMA) is autosomal recessive mutations in the _____ gene. Progressive ___ ___. Assembly of ____. There are four subtypes.
SMN1 (survival motor neuron 1)
Muscle weakness
snRNPs
Spinal muscular dystrophy evolutionary duplication in a second gene ___, identical to SMN1 apart from __ nucleotides. It causes aberrant splicing and skipping of _____.
____ promotes SMN2 exon 7 inclusion. Intrathecal administration. Given every 4 months.
SMN2
5
Exon 7
Nusinerson
Duchenne muscular dystrophy is and Xlinked disease characterized by progressive ___ ___ and ____. Causes by a frameshift of nonsense mutations in ____. Treatment is ____, once weekly IV treatment
Muscular wasting
Cardiomyopathy
DMD
Eteplirsen/Exondys 51
Small interfering RNA (siRNA) are small __ ___ RNA. It divides into single strand and binds to target ___. They are helpful in gain of function disorders.
Double stranded
mRNA
Hereditary transthyretin Amyloidosis is an autosomal dominant disease with a mutation in ___, causing accumulation of ____. Symptoms are sensorimotor neuropathy, renal, cardiac, and GI dysfunction. ____ (siRNA) for treatment, helps the cleavage of mRNA.
TTR
amyloid
Patisiran
Stem cell therapy is ___ medicine that utilized stem cells to become ____ to differentiate into specific cellular lineages. Various types of stem cells used:
Regenerative
Programmed
____ stem cells transplant (HSCT) involves the transplantation of stem cells from the __ ___, __ ___, or ___ __ blood.
Hematopoietic
Bone marrow
Peripheral blood
Umbilical cord blood
Lupus, SCID, leukemia, sickle cell, lysosomal disorders are all treated with ____ ___ ___ ___.
Hematopoietic Stem Cell Transplant (HSCT)
HSCT advantages and disadvantages:
___ stem cells are capable of differentiating into any cell type. There are no current FDA approved drugs for this.
Embryonic
Embryonic stem cell advantages and disadvantages:
Induced pluripotent stem cells (iPSCs) are generated by ____ adult somatic cells. No current FDA approved drugs. There are no ___ considerations with this type.
Reprogramming
Ethical
Induced pluripotent stem cells (iPSCs) advantages and disadvantages:
Gene therapy uses a gene to treat or prevent or cure a disease. Usually adds __ __ of a gene that is mutated or ___ the defective gene.
New copies
Replaces
Common vehicles for gene therapy are ___ virus, ___ ___ virus, and ____.
Adeno
Adeno-associated
Retrovirus
Viral versus non-viral vectors:
___ ___ gene therapy is less invasion than ex vivo. There is the possibility of an ___ reaction and it is ___.
In vivo
Immune
Costly
___ ___ gene therapy involves removing the __ __ and manipulating them and then readministering them. Less likely ___ reaction, potential for ___ ___ and it costly.
Ex vivo
Patient’s cells
Immune
Clonal expansion
Review:
Summary:
