Treatments of Genetic Disease

Question 1

Substrate modulation strategies:

Answer 1

Dietary restrictions
Toxin removal
Metabolic manipulation

Question 2

Dietary restriction is when you restrict consumption of the offending ____. Examples of disease targets:

Answer 2

Substrate

PKU
organic acidemias
Carbohydrate disease
Fatty acid oxidation disease

Question 3

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

Answer 3

Phenylalanine
Phenylalanine
Phenylalanine

Question 4

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.

Answer 4

Degradation
Removal
Ammonia-scavenging

Question 5

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.

Answer 5

X-linked Adrenoleukodystrophy
ABCD1
VLCFA
SCD1 (stearoyal-CoA desaturase-1)
Chloroquine

Question 6

Substrate reduction therapy blocks a ___ ___ in order to reduce the build up of molecule. _____ is used to reduce the substrate.

Answer 6

Normal enzyme
Eligustat

Question 7

Advantages and disadvantages of dietary restriction:

Answer 7

Question 8

Advantages and disadvantages of toxin removal:

Answer 8

Question 9

Advantages and disadvantage of substrate reduction therapy:

Answer 9

Question 10

Product supplementation is mostly dietary supplements that provide ___ ____ directly or act as ____ to prevent toxic accumulations. Examples:

Answer 10

Missing compounds
Alternates

Biotin
Pyridoxal phosphate
Betaine for homocystinuria
Dojolvi

Question 11

Cofactor replacement or supplement ____ endogenous activity. It is mostly oral administration. Examples:

Answer 11

Enhances

Tetrahydrobiopterin (BH4) used in PKU

Palynziq is a substitute for the deficient PAH

Question 12

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

Answer 12

Hemophilia
Antibodies

Question 13

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.

Answer 13

Lifelong
Allogeneic
Gene therapy

Question 14

Examples of enzyme replacement therapy medications:

Answer 14

Question 15

____ 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.

Answer 15

Chaperone
Heat shock
Galafold
Ambroxol

Question 16

Cystic fibrosis transmembrane regulator gene (CFTR) is ____ which regulates the flow of ____ ions across the cell membrane. CFT Modulators as treatment:

Answer 16

Mutated
Chlorine

Question 17

____ is used for sickle cell disease. It increases the amount of fetal hemoglobin. It is ___ ___/___ ___

Answer 17

Hydroxyurea

Protein replacement/metabolic manipulation

Question 18

Advantages and disadvantages of enzyme replacement therapy:

Answer 18

Question 19

Advantages and disadvantages of chaperone therapy:

Answer 19

Question 20

Gene modification therapies:
1.
2.

Answer 20

Antisense oligonucleotides (ASOs)
Small interfering RNA (siRNA)

Question 21

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

Answer 21

Synthetic
RNA
Duchenne muscular dystrophy
Spinal muscular atrophy
Blood brain barrier
Intrathecal
Intraventricular

Question 22

ASO methods:
Target degradation and blocking the binding of RNA binding ____ gene expression.

Answer 22

Inhibits

Question 23

ASO methods:
Helps in exon skipping or inclusion and increases the amount of protein translated from a downstream ORF both ___ gene expression.

Answer 23

Increase

Question 24

Spinal muscular atrophy (SMA) is autosomal recessive mutations in the _____ gene. Progressive ___ ___. Assembly of ____. There are four subtypes.

Answer 24

SMN1 (survival motor neuron 1)
Muscle weakness
snRNPs

Question 25

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.

Answer 25

SMN2 5 Exon 7 Nusinerson

Question 26

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

Answer 26

Muscular wasting Cardiomyopathy DMD Eteplirsen/Exondys 51

Question 27

Small interfering RNA (siRNA) are small __ ___ RNA. It divides into single strand and binds to target ___. They are helpful in gain of function disorders.

Answer 27

Double stranded mRNA

Question 28

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.

Answer 28

TTR amyloid Patisiran

Question 29

Stem cell therapy is ___ medicine that utilized stem cells to become ____ to differentiate into specific cellular lineages. Various types of stem cells used:

Answer 29

Regenerative Programmed

Question 30

____ stem cells transplant (HSCT) involves the transplantation of stem cells from the __ ___, __ ___, or ___ __ blood.

Answer 30

Hematopoietic Bone marrow Peripheral blood Umbilical cord blood

Question 31

Lupus, SCID, leukemia, sickle cell, lysosomal disorders are all treated with ____ ___ ___ ___.

Answer 31

Hematopoietic Stem Cell Transplant (HSCT)

Question 32

HSCT advantages and disadvantages:

Answer 32

Question 33

___ stem cells are capable of differentiating into any cell type. There are no current FDA approved drugs for this.

Answer 33

Embryonic

Question 34

Embryonic stem cell advantages and disadvantages:

Answer 34

Question 35

Induced pluripotent stem cells (iPSCs) are generated by ____ adult somatic cells. No current FDA approved drugs. There are no ___ considerations with this type.

Answer 35

Reprogramming Ethical

Question 36

Induced pluripotent stem cells (iPSCs) advantages and disadvantages:

Answer 36

Question 37

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.

Answer 37

New copies Replaces

Question 38

Common vehicles for gene therapy are ___ virus, ___ ___ virus, and ____.

Answer 38

Adeno Adeno-associated Retrovirus

Question 39

Viral versus non-viral vectors:

Answer 39

Question 40

___ ___ gene therapy is less invasion than ex vivo. There is the possibility of an ___ reaction and it is ___.

Answer 40

In vivo Immune Costly

Question 41

___ ___ gene therapy involves removing the __ __ and manipulating them and then readministering them. Less likely ___ reaction, potential for ___ ___ and it costly.

Answer 41

Ex vivo Patient’s cells Immune Clonal expansion

Question 42

Review:

Answer 42

Question 43

Summary:

Answer 43