Q1
a. Mass spectrometry can generate high-resolution images that depict the distribution of
various proteins in tissue sections. By coating the tissue section with a 50-150µm MALDI
matrix, which is sprayed onto the surface and amplified by laser firing across the deposits, a
spectral signal image of the tissue sample can be generated and compared to a database to
produce the tissue image.
b. The m/z is the mass-to-charge ratio. m is the mass and z is the charge number of ions.
c. Drug A is suitable for clinical trials as it is the only drug that has shown efficacy against all
stages of tumor growth, and its concentration test (10) has yielded favorable results.
Additionally, the comparison of four sample states (which showed positive results) to the
control (which demonstrated an obvious negative result) is statistically significant.
d. Patient 1 represents the initial stage of tumor progression as all drugs are effective against
it. Patient 3 is in the intermediate stage as all drugs, except drug D, can still be used to target
it. Patients 2 and 4 are in the advanced stages as only one drug can be used to target them.
Q2
1. Givosiran is a siRNA which is a double-stranded RNA which can attach with target mRNA
to silence it.
2. Attach three N-acetylgalactosamine (GalNAc) molecules to Givosiran siRNA can make the
siRNA enter into the hepatocytes rapidly because the GalNAc can binds the asialoglycoprotein
receptor (ASGR) with high affinity.
3. aminolevulinic acid and porphobilinogen.
4. The decreased levels of aminolevulinic acid and porphobilinogen can confirm that the
ALAS1 expression was inhibited by the Givosiran via silencing the mRNA of ALAS1 to reduce
the enzyme production in the heme biosynthesis pathway.
Q3
1. Pharmacological chaperone
2. Migalastat can binds with certain mutated aGAL to stabilized it from misfolding to facilitate
the catabolysis of substrate of aGAL to reduce the accumulation of the substrate.
3. Sunder-Plassmann’s (2018) clinical trials identified that although migalastat is related with
headache, left ventricular hypertrophy and left ventricular index decrease in the long term
treatment, migalastat can effectively reduces many symptoms of Fabry disease such as
dicreasing disease substrate accumulation, stabilizing renal function, decreasing cardiac mass
and improving gastrointestinal signs.
Reference list:
Sunder-Plassmann, G., Schiffmann, R., & Nicholls, K. (2018). Migalastat for the treatment of
Fabry disease. Expert Opinion on Orphan Drugs, 6(5), 301 – 309.
https://doi.org/10.1080/21678707.2018.1469978
4. Although organs are physically independent in organisms, the communications via blood
and lymph are still very frequent, sometimes the toxicity will occur in the secondary tissue but
not the target tissue after process of absorption/distribution/metabolism/excretion/toxicity
(ADMET) (Picollet-D’hahan, N, 2021).
As a result, it is better to test the drug in the multi-organ model to mimic the efficacy and
toxicity in the post-clinical trials.
Reference list:
Picollet-D’hahan, N., Zuchowska, A., Lemeunier, I., & Le Gac, S. (2021). Multiorgan-on-a-Chip:
A Systemic Approach To Model and Decipher Inter-Organ Communication. Trends in
Biotechnology, 39(8), 788–810. https://doi.org/10.1016/j.tibtech.2020.11.014