Treatments of Genetic Disease Flashcards

1
Q

Substrate modulation strategies:

A

Dietary restrictions
Toxin removal
Metabolic manipulation

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2
Q

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

A

Substrate

PKU
organic acidemias
Carbohydrate disease
Fatty acid oxidation disease

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3
Q

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

A

Phenylalanine
Phenylalanine
Phenylalanine

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4
Q

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.

A

Degradation
Removal
Ammonia-scavenging

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5
Q

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.

A

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

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6
Q

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

A

Normal enzyme
Eligustat

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7
Q

Advantages and disadvantages of dietary restriction:

A
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8
Q

Advantages and disadvantages of toxin removal:

A
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9
Q

Advantages and disadvantage of substrate reduction therapy:

A
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10
Q

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

A

Missing compounds
Alternates

Biotin
Pyridoxal phosphate
Betaine for homocystinuria
Dojolvi

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11
Q

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

A

Enhances

Tetrahydrobiopterin (BH4) used in PKU

Palynziq is a substitute for the deficient PAH

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12
Q

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

A

Hemophilia
Antibodies

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13
Q

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.

A

Lifelong
Allogeneic
Gene therapy

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14
Q

Examples of enzyme replacement therapy medications:

A
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15
Q

____ 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.

A

Chaperone
Heat shock
Galafold
Ambroxol

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16
Q

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

A

Mutated
Chlorine

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17
Q

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

A

Hydroxyurea

Protein replacement/metabolic manipulation

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18
Q

Advantages and disadvantages of enzyme replacement therapy:

A
19
Q

Advantages and disadvantages of chaperone therapy:

A
20
Q

Gene modification therapies:
1.
2.

A

Antisense oligonucleotides (ASOs)
Small interfering RNA (siRNA)

21
Q

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

A

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

22
Q

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

A

Inhibits

23
Q

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

A

Increase

24
Q

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

A

SMN1 (survival motor neuron 1)
Muscle weakness
snRNPs

25
Q

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.

A

SMN2
5
Exon 7

Nusinerson

26
Q

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

A

Muscular wasting
Cardiomyopathy
DMD
Eteplirsen/Exondys 51

27
Q

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

A

Double stranded
mRNA

28
Q

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.

A

TTR
amyloid
Patisiran

29
Q

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

A

Regenerative
Programmed

30
Q

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

A

Hematopoietic
Bone marrow
Peripheral blood
Umbilical cord blood

31
Q

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

A

Hematopoietic Stem Cell Transplant (HSCT)

32
Q

HSCT advantages and disadvantages:

A
33
Q

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

A

Embryonic

34
Q

Embryonic stem cell advantages and disadvantages:

A
35
Q

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

A

Reprogramming
Ethical

36
Q

Induced pluripotent stem cells (iPSCs) advantages and disadvantages:

A
37
Q

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.

A

New copies
Replaces

38
Q

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

A

Adeno
Adeno-associated
Retrovirus

39
Q

Viral versus non-viral vectors:

A
40
Q

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

A

In vivo
Immune
Costly

41
Q

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

A

Ex vivo
Patient’s cells
Immune
Clonal expansion

42
Q

Review:

A
43
Q

Summary:

A