2023/3/24 15:24 Quiz: MCHM3X01 Test 1 (2023)
https://canvas.sydney.edu.au/courses/49192/quizzes/215136/take 1/5
MCHM3X01 Test 1 (2023)
Started: Mar 24 at 15:23
Quiz Instructions
This is Test 1. Material from all aspects of the lectures in weeks 1-4 may be examined in this test.
It is an online, open-book test.
The questions will be available on Tuesday 21 March from 1:00 pm and close on Friday 24 March
2023 at 11:59 pm (just before midnight). You must submit your answers below by 11:59 pm on 24
March 2023.
You will be required to write short answers to a series of questions, into the free text fields below for
submission. It is strongly recommended you prepare your answers in another document, then paste
your final answers below for submission.
Once you start the test, you will have 1-hour (plus 10 min reading time) to complete the test and can
return to the test multiple times within the 1-hour period. Only your highest attempt will be marked.
12 ptsQuestion 1
The Figure shows Mass Spectrometry Imaging (MSI) data on 4
drug compounds (Drug A, B, C, D) that bind different targets in
human tumours. The ‘Unknown’ tissue samples are from 4
2023/3/24 15:24 Quiz: MCHM3X01 Test 1 (2023)
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patients with tumours at different stages of growth. The "Control'
is a negative control. 'Calibration standards’ are small tissue
samples with various concentrations of each drug spiked in.
a. Describe Mass Spectrometry Imaging using technical detail. (4
marks)
b. What is m/z? (2 marks)
c. Which of the 4 drug compounds do you choose to progress to
clinical trial based on the data, and why? (4 marks)
d. Can you make any comments about patient tumour progression
based on the data provided? (2 marks)
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8 ptsQuestion 2
Givosiran is a new RNA interference therapy for the treatment of
porphyria. Porphyrias are rare and severe disorders of heme
biosynthesis. Patients suffering acute hepatic porphyria
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2023/3/24 15:24 Quiz: MCHM3X01 Test 1 (2023)
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experience attacks involving severe abdominal pain, vomiting
and tachycardia. These attacks are caused by upregulation of the
rate-limiting enzyme in the heme biosynthesis pathway,
aminolevulinic acid synthase 1 (ALAS1), which leads to
accumulation of neurotoxic metabolites aminolevulinic acid and
porphobilinogen. A Phase III clinical trial of givosiran in 2020
showed that patients who received givosiran experienced
significantly lower rate of porphyria attacks than those who
received a placebo.
a. What type of RNA molecule is givosiran? (1 mark)
b. Explain the rationale for attachment of three N-acetylgalactosamine
residues to the givosiran molecule. (2 marks)
c. Identify two endogenous biomolecules that you could measure to
determine the efficacy of givosiran treatment in patients? (2 marks)
d. How would you expect the levels of these two biomolecules to
change with these treatments? Include in your answer an explanation
about how these changes reflect the mechanism of action of givosiran.
(3 marks)
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10 ptsQuestion 3
Certain mutations in the gene for alpha-galactosidase (aGAL)
cause Fabry disease. These mutations result in misfolding of
aGAL and its accumulation in the endoplasmic reticulum,
followed by degradation. The options for the treatment of Fabry
disease have been increased by modern approaches to
“expanding the druggable proteome”. Migalastat is an analogue
of galactose. It has been approved for the treatment of Fabry
disease in patients with suitable aGAL mutations.
a. What class of drug does migalastat belong to? (1 mark)
b. Briefly describe the mechanism of action of migalastat - i.e. in
general terms how does it reduce the effect of the mutations. (3 marks)
c. Does treatment with migalastat provide benefit to patients? Justify
your conclusion with a reference to one published report that supports
your answer. (2 marks)
A drug company has developed a modified compound that they
think will be more effective than migalastat at preventing the
accumulation of misfolded aGAL in the kidney. They are
concerned that 2D in vitro cultures may not be the best model
system for testing the efficacy and renal toxicity of the drug.
d. What would you propose to use as a model system that is a better
representative of the kidney as a target organ? Provide a reference to
a scientific publication that supports your choice. (4 marks)
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