Treatment of genetic diseases in the present

Question 1

most treatment strategies for genetic disorders do not

Answer 1

alter the underlying genetic mutation.

Question 2

preventitive therapy for genetic diseases

Answer 2

carrier screening and prenatal diagnosis

preimplantation diagnosis

Question 3

therapeutic approaches for inherited metabolic diseases: currently available

Answer 3

metabolic manipulation
protein/enzyme replacement
cell/organ transplantation

Question 4

therapeutic approaches for inherited metabolic diseases: under development

Answer 4

pharmacologic chaperones
RNA interference
gene therapy
genome editing
stem cell therapy

Question 5

PKU cofactor supplementation

Answer 5

Kuvan for tetrahydrobiopterin (B4).

it is a B4 cofactor.

Question 6

PKU alternative enzyme for substrate clerance

Answer 6

PEG-PAL (pegylated recombinant phenylalanine ammonia lyase)

Question 7

PEG-PAL

Answer 7

a phenylalanine ammonia lyase that breaks down phenylalaine to harmless components.
Treatment does not work in all patients

Question 8

pegylating something means

Answer 8

coating it in a substanced called PEG. it masks the substance from the host’s immune system, preventing an immune/allergic response. it helps the substance last longer.

Question 9

urea cycle defects (UCDs) treatment strategies

Answer 9

dietary management (special amino acid formulas)
buphenyl (sodium phenylbutyrate)
liver transplant

Question 10

principles of UCD treatment

Answer 10

restrict substrate: special amino acid formulas
provide cofactors N-carbamylglutamate
provide product: arginine fro distal defects, citralline for proximal defects
provide alternative elimination routes.

Question 11

homocystinuria: mode of inheritance

Answer 11

autosomal recessive

Question 12

homocystinuria: pathology

Answer 12

reduced activity of cystathionine beta-synthase
accumulation of homocystein and methionine interfere with collage cross linking.
increased cardiovascular risk increased in heterozygote.

Question 13

homocystinuria: treatment

Answer 13

methionine restriction, cyteine and pyridoxine supplements

Question 14

__% of homocystinuria patients respond to pyridoxine treatment.

Answer 14

50%

Question 15

obstacles to enzyme replacement in lysosomal disorders

Answer 15

inability to produce large quantities of pure human enzymes.

inability to target enzymes to key sites of pathology, especially to the brain and bone.

lack of animal models for pre-clinical trials

concern for possible immunologic reactions

Question 16

principles for effect ERT: enzyme delivery is

Answer 16

receptor mediated and dose dependent.

Uptake depends on receptor density on cell membranes.

Question 17

gaucher, type 1: areas easier and harder to reach

Answer 17

easy: liver, spleen
hard: bone

Question 18

fabry: easier and hearderto reach

Answer 18

easy: endothelium
hard: kidney, heart

Question 19

MPS I, II, VI: easier and harder to reach

Answer 19

easy: liver, spleen
hard: bone, brain, cartilage

Question 20

pompe: easier and harder to reach

Answer 20

easy: smooth muscle
hard: skeletal muscle

Question 21

the metabolic defect in gaucher disease

Answer 21

glycosyl ceramide is broken into glucose and ceramide by acid beta-glucosidase (glucocerebrosidase)

Question 22

gaucher disease type 1

Answer 22

onset: childhood/adult
hepathosplenomegaly
hypersplenism
bone fractures
no neurodegeneration
ethnic predilection: Ashkenazi Jewish

Question 23

gaucher disease type 2

Answer 23

onet: infancy
hepatosplenomegaly
hypersplenism
no bone fractures
neurodegenration
ethnic prediction: panethnic

Question 24

gaucher disease type 3

Answer 24

onset: juvenile
hepatosplenomegaly
hypersplenism
bone fractures
neurodegenration
death 2 - 4th decade
ethnic predilection: swedish

Question 25

glucocerebrosidase distribution in rat eliver

Answer 25

the highets amount of mannose terminated is found in non-parenchymal cells

Question 26

enzyme replacement therapy in type 1 gaucher disease

Answer 26

increased hemoglobin
increased leukocyte and latelet counts
decreased spleen and liver volume
decreased bone crises; improved skeleton
decreased fatigue

Question 27

enzyme therapy in type I gaucher disease

Answer 27

it reverses lysosomal storage but is ineffective for neurologic disease

Question 28

lessons learned from ERT for gaucher disease

Answer 28

ERT works!

dose dependent enzyme delivery:
receptor mediated enzyme uptake: mannose
inability to cross blood-brain barrier

Question 29

enzyme replacement therapy prevents progressive manifestations of

Answer 29

Gaucher disease, and ameliorates Gaucher disease associated anemia, thrombocytopenia, organomegaly, bone pain and bone crises.

Question 30

pluripotent hematopoietic stem cells example

Answer 30

a bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.

Question 31

autologous transplant

Answer 31

stem cells are removed from the patient before high dose chemotherapy or radiation treatment. After chemotherapy your stem cells are put back in your body to make normal blood cells.

Question 32

allogenic transplant

Answer 32

stem cells are removed from another person, called a donor. Donor’s genes must at least partly match your genes.

Question 33

umbilical cord blood transplant

Answer 33

stem cells are removed from a newborn baby’s umbilical cord right after birth. The stem cells are frozen and stored until they are needed for a transplant. These cells are very immature so there is less of a need for matching.

Question 34

advantages of cord blood versus matched donor

Answer 34

easy to obtain and store
less stringent matching requirements
fewer graft versus host reactions