Cell depletion therapy

Question 1

Discuss Sphingosine-1-phosphate

Answer 1

• A signalling lipid produced by the plasma membrane.

Question 2

What are S1P Receptors?

Answer 2

• A class of G protein-coupled receptors that are targets of Sphingosine-1-phosphate.

Question 3

What is the function of S1P?

Answer 3

• S1P regulates lymphocyte trafficking in immunity and allergy by attracting the lymphocytes to migrate via various receptors.

Question 4

What is the MOA of Fingolimod (FTY720)?

Answer 4

• Derivative of fungal isolate (Isaria sinclairii).
• Orally active S1P1 receptor agonist, requires phosphorylation.
• Causes receptor internalization:
• Prevents egress of lymphocytes from lymphoid tissue in response to S1P.
• Reduces lymphocyte levels.
• Reduces hyperactivity of astrocytes.

Question 5

What are the adverse effects of Fingolimod?

Answer 5

• Effects on heart rate and conduction.
• Macular oedema.
• 7 cases of skin cancers.
• 1 definite case and 2 probable cases of PML.
• Increased infections: 2 deaths from herpes virus infections.

Question 6

What is the MOA of Siponimod?

Answer 6

• Next generation S1P1 antagonist
• Selective for S1P1 & S1P5
• Fingolimod binds S1P 1,3,4&5
• Approved for MS

Question 7

What is CD52 and what targets it?

Answer 7

• Found on mature lymphocytes.
• Alemtuzumab is a monoclonal antibody against CD52.
• Used for relapsing-remitting MS and T-cell leukaemia.
• Potential for treatment of HIV?
• Can lead to increase in autoimmune disease.