Molecular therapy lectures
Name: Abduallah Lemdjad
Course: Molecular therapies
Study year: 2023/2024
,Table of Contents
Lecture 1 – Personalized healthcare .................................................................................. 4
Lecture 2 – Pharmacodynamics and pharmacokinetics ...................................................... 4
2.1 Volume distribution ............................................................................................................ 5
2.2 T half-life ............................................................................................................................ 5
2.3 Steady state concentration .................................................................................................. 5
Lecture 3 – Biotransformation ........................................................................................... 6
Phase I reactions....................................................................................................................... 6
Phase II reactions...................................................................................................................... 7
Lecture 4 – Transport proteins ........................................................................................... 7
Lecture 5 – Drug targeting and delivery (part I) ................................................................. 8
Nanoparticles – liposomes ........................................................................................................ 9
How to make liposomes ................................................................................................................................. 9
Lecture 6 – Drug targeting and delivery (part II) .............................................................. 11
Antibody drugs conjugate ....................................................................................................... 11
Immunocytokines ................................................................................................................... 12
Oligonucleotides ..................................................................................................................... 12
Lecture 7 – Drug development ......................................................................................... 14
Target selection ...................................................................................................................... 15
Hit identification ..................................................................................................................... 15
Hit-to-lead/lead identification ................................................................................................. 15
Lead optimization ................................................................................................................... 15
Lecture 8 – Genetic therapy for retinal disease ................................................................ 16
Inherited retinal disease ......................................................................................................... 16
The RPE65 story ...................................................................................................................... 17
Lecture 9 – Splicing modulation therapy .......................................................................... 18
AON-based therapy for CEP290-assocaited LCA ....................................................................... 18
Stargardt disease .................................................................................................................... 18
Lecture 10 - Genome editing therapy ............................................................................... 19
Lecture 11 – Renal physiology ......................................................................................... 20
Reabsorption and secretion ......................................................................................................................... 20
The renal corpuscle ...................................................................................................................................... 20
The vascular pole and the tubular pole ........................................................................................................ 20
The juxtaglomerular apparatus .................................................................................................................... 22
Lecture 12 – Drug-induced renal pathologies ................................................................... 23
,Lecture 13 - Receptor tyrosine kinase .............................................................................. 24
Lecture 14 – Modern cancer therapies ............................................................................. 26
Lecture 15 – GPCR-mediated signaling ............................................................................ 28
GPCR regulation of PKC ........................................................................................................... 29
Homologous desensitization through GRK2 ............................................................................. 29
Lecture 16 – Pain management, focus on GPCR ............................................................... 30
, Lecture 1 – Personalized healthcare
Personalized diagnosis, therapy and participation make up their personalized healthcare. The first
step when a patient is admitted to the hospital is a genetic screening (Whole Exosome Sequencing).
After that a metabolic screening is performed. The metabolic screening indicated that there was a too
high level of orotic acid due to uridine monophosphate synthase deficiency.
Multiple myeloma is characterized by monoclonal plasma cells over producing M proteins. Is
diagnosed via gel electrophoresis, where a clear band is visible caused by gamma chains. Minimal
Residual Disease
Lecture 2 – Pharmacodynamics and pharmacokinetics
Pharmacokinetics is what does the patient do with the drug and pharmacodynamics is what does the
drug do with the patient (what is the effect of the drug on the patient). In mechanism-based
pharmacotherapy, the mechanism is determined, and a drug is used/developed to interfere with this
mechanism. In evidence-based pharmacotherapy, the drug that is used is effective however the
mechanism is unknown (for example paracetamol). Agonist binds and stimulates a receptor, while an
antagonist binds and supresses a receptor. Receptors can be divided into four groups:
1. Ligand-gated ion channels
2. G protein-coupled receptor
3. Nuclear receptor
4. Kinase-linked receptor
With a non-competitive antagonist, the 100% efficiency can never be reached.
All substances are poisons, it is the dose and the exposure that determines whether the substance is
toxic. Exposure to toxins is determined by metabolism and transport (toxicokinetic). There are two
types of toxic exposure on the human body: systemic exposure and tissue exposure. Toxicokinetic is
regarded as the movement of xenobiotics through your body. Exposure of toxic substances usually goes
through inhalation, ingestion and skin contact.
Name: Abduallah Lemdjad
Course: Molecular therapies
Study year: 2023/2024
,Table of Contents
Lecture 1 – Personalized healthcare .................................................................................. 4
Lecture 2 – Pharmacodynamics and pharmacokinetics ...................................................... 4
2.1 Volume distribution ............................................................................................................ 5
2.2 T half-life ............................................................................................................................ 5
2.3 Steady state concentration .................................................................................................. 5
Lecture 3 – Biotransformation ........................................................................................... 6
Phase I reactions....................................................................................................................... 6
Phase II reactions...................................................................................................................... 7
Lecture 4 – Transport proteins ........................................................................................... 7
Lecture 5 – Drug targeting and delivery (part I) ................................................................. 8
Nanoparticles – liposomes ........................................................................................................ 9
How to make liposomes ................................................................................................................................. 9
Lecture 6 – Drug targeting and delivery (part II) .............................................................. 11
Antibody drugs conjugate ....................................................................................................... 11
Immunocytokines ................................................................................................................... 12
Oligonucleotides ..................................................................................................................... 12
Lecture 7 – Drug development ......................................................................................... 14
Target selection ...................................................................................................................... 15
Hit identification ..................................................................................................................... 15
Hit-to-lead/lead identification ................................................................................................. 15
Lead optimization ................................................................................................................... 15
Lecture 8 – Genetic therapy for retinal disease ................................................................ 16
Inherited retinal disease ......................................................................................................... 16
The RPE65 story ...................................................................................................................... 17
Lecture 9 – Splicing modulation therapy .......................................................................... 18
AON-based therapy for CEP290-assocaited LCA ....................................................................... 18
Stargardt disease .................................................................................................................... 18
Lecture 10 - Genome editing therapy ............................................................................... 19
Lecture 11 – Renal physiology ......................................................................................... 20
Reabsorption and secretion ......................................................................................................................... 20
The renal corpuscle ...................................................................................................................................... 20
The vascular pole and the tubular pole ........................................................................................................ 20
The juxtaglomerular apparatus .................................................................................................................... 22
Lecture 12 – Drug-induced renal pathologies ................................................................... 23
,Lecture 13 - Receptor tyrosine kinase .............................................................................. 24
Lecture 14 – Modern cancer therapies ............................................................................. 26
Lecture 15 – GPCR-mediated signaling ............................................................................ 28
GPCR regulation of PKC ........................................................................................................... 29
Homologous desensitization through GRK2 ............................................................................. 29
Lecture 16 – Pain management, focus on GPCR ............................................................... 30
, Lecture 1 – Personalized healthcare
Personalized diagnosis, therapy and participation make up their personalized healthcare. The first
step when a patient is admitted to the hospital is a genetic screening (Whole Exosome Sequencing).
After that a metabolic screening is performed. The metabolic screening indicated that there was a too
high level of orotic acid due to uridine monophosphate synthase deficiency.
Multiple myeloma is characterized by monoclonal plasma cells over producing M proteins. Is
diagnosed via gel electrophoresis, where a clear band is visible caused by gamma chains. Minimal
Residual Disease
Lecture 2 – Pharmacodynamics and pharmacokinetics
Pharmacokinetics is what does the patient do with the drug and pharmacodynamics is what does the
drug do with the patient (what is the effect of the drug on the patient). In mechanism-based
pharmacotherapy, the mechanism is determined, and a drug is used/developed to interfere with this
mechanism. In evidence-based pharmacotherapy, the drug that is used is effective however the
mechanism is unknown (for example paracetamol). Agonist binds and stimulates a receptor, while an
antagonist binds and supresses a receptor. Receptors can be divided into four groups:
1. Ligand-gated ion channels
2. G protein-coupled receptor
3. Nuclear receptor
4. Kinase-linked receptor
With a non-competitive antagonist, the 100% efficiency can never be reached.
All substances are poisons, it is the dose and the exposure that determines whether the substance is
toxic. Exposure to toxins is determined by metabolism and transport (toxicokinetic). There are two
types of toxic exposure on the human body: systemic exposure and tissue exposure. Toxicokinetic is
regarded as the movement of xenobiotics through your body. Exposure of toxic substances usually goes
through inhalation, ingestion and skin contact.
