100% tevredenheidsgarantie Direct beschikbaar na betaling Zowel online als in PDF Je zit nergens aan vast
logo-home
Summary Molecular Therapy €5,99   In winkelwagen

Samenvatting

Summary Molecular Therapy

 17 keer bekeken  0 keer verkocht

Summary of all the Molecular therapy lectures

Voorbeeld 4 van de 85  pagina's

  • 16 november 2023
  • 85
  • 2023/2024
  • Samenvatting
Alle documenten voor dit vak (11)
avatar-seller
stellav19
PHARMACODYNAMICS & -KINETICS


LE: PERSONALIZED HEALTHCARE

ROLE OF MOLECULAR (OMICS) BIOMARKER DATA IN PERSONALIZED HEALTHCARE

Vicious circle of patient → X-omics → personalized healthcare (= personalized diagnosis, therapy and
participation) → therapy monitoring → patient

PERSONALIZED HEALTHCARE IN RARE METABOLIC DISEASES

Diagnosis:

- Genetic screening: tri whole exome sequencing (mother, father, child)
- Metabolic screening: e.g. urine analysis

→ genetic metabolic disorder = inborn errors of the metabolism

e.g. Uridine monophosphate synthase (UMPS) deficiency:

- personalized diagnosis: high orotic acid
- personalized therapy: uridine supplementation
- however: route to therapeutic drug difficult (import, insurances)
o alternative: food supplementation @ local drug store

Lessons learned:

- on personal diagnosis: technology innovation is driving impact in personalized healthcare &
combination of genetic and metabolic screening is a strong approach towards identifying mechanism
of disease
- on personalized medicine: impressive effect of uridine therapy, increase quality of life for patient and
family & frequent issues regarding expensive medication vs cheap supplements

Other story: personalized healthcare in multiple myeloma

- 2nd most common haematological malignancy
- Monoclonal plasma cells in bone marrow that secrete a M protein
- Treated by chemo, steroids and specific drugs
- ~50% of patients achieve minimal residual disease (MRD)
- Need to restart therapy as soon as disease relapses
- Diagnostic test for MM: blood M-protein gel electrophoresis
- Current test for MRD: isolate bone marrow, analysis stromal cells by flow cytometry or genomics (PCR,
NGS)
o Problems: cumbersome and invasive procedure for repetitive monitoring & sampling error
caused by tumour heterogeneity
o Can we use plasma proteomics to monitor MRD?
▪ Approach: direct measurement of rearranged region of the M-protein targeted
proteomics in plasma samples (= MS MRD method)
• Mass spectrometry strongly increases sensitivity detection M-protein as it is
feasible for monitoring and early detection relapses & re-analysis of
archived gels possible
▪ Parallel reaction monitoring (PRM)

1

, o Conclusion: sequencing-MRD vs mass spectrometry-MRD: similar sensitivity & perform
equally well as prognostic marker

Lessons learned:

- Technology innovation is driving impact in personalized healthcare
- Analysis of dynamic biomarkers is key in monitoring Minimal Residual Disease to:
- Mass spectrometry has added value and good potential here
- Collaboration between clinic, lab specialists, proteomics labs + between academics and industry is
needed and works!
o Analytical development
o Clinical validation
 Clinical omics data to drive personalized healthcare: personalized analysis → diagnosis of (new)
disease mechanisms → initiation and monitoring of (new) personalized therapies

DIGITAL BIOMARKERS

e.g. smartwatch, minion, etc

Advantages digital biomarkers

- Continuous monitoring versus 1 snapshot observation
- Real world data versus data from clinically controlled circumstances
- More comprehensive and rich data sets
- Truely personalized
- Strong potential in molecular + clinical + digital + environmental biomarkers for optimal insight in
complex biological systems
- Better basis to drive Personalized health(care)
- Better support for phase 1, 2, 3, 4 clinical trials

Digital biomarkers enable personalized health monitoring: past (population) → present (subgroups) → future
(individual data through self-monitoring)

Wearables: personalized Parkinson project

- Bas Bloem, The personalized Parkinson Project: examining disease progression through broad
biomarkers in early Parkinson’s disease
o Verily study watch: Scheduled tasks: e.g. seated rest, hand opening
o Enables frequent and reliable remote measurements of motor function

Personalized health(care) model

- Primary prevention: avoiding disease
- Secondary prevention: screening to identify
disease the earliest
- Tertiary prevention: managing disease post
diagnosis to stop or slow

A personalized data-driven GPS for health

- Monitor on background
- Alert when you are at risk



2

, - Advice what to do, Doctor as coach?

3 INNOVATION GAPS

- Research to research
- Research to clinic
o Numerous biomarkers are discovered → only few being validated/confirmed → only fewer
being diagnostic tested (whole pathway takes a lot of time)
▪ Also goes for the digital markers, e.g. smartphone app detects bacteria/diseases
o Also quality issues in commercial health biomarker analysis, e.g. 23andMe ‘post-traumatic
test syndrome’ of medical advice falsely given by the company
- Research to society

Big hopes for big data, but.. crap data will remain crap data even if mare FAIR (findable accessible
interoperable reusable) and AI-ready

- Publication bias: the failure to publish the results of a study on the basis of the direction or strength of
the study findings.
- Funding bias: the tendency of a scientific study to support the interests of the study's financial
sponsor.

Choice for scientists: discover or confirm?

Most importantly: always focus on the end user: patient/citizen

➔ Big debate about ethical, legal, societal aspects

Afterthought: there is no single reflection of health

- ‘Funhouse mirror effect’: everything reflects you
- Multiple sources of your data
o Clinical chemistry
o Omics analyses
o Digital biomarkers/ wearables
o Self-testing health checks
o Social media
o Surrounding
- Each are a skewed image of you
- How to deal with all of this for your personal health(care)

LE: PHARMACODYNAMICS AND PHARMACOKINETICS

- Everything is poison depending on the dose (Paracelsus)
- Pharmacology = the science that is concerned with the uses, effects and modes of action of chemicals
on the function of living systems
- There are different levels to pharmacology: molecule, cell, organ, organism, family, population →
Pharmacotherapy focusses on patients

PHARMACOTHERAPY

- What does the patient do with the drug: pharmacokinetics; e.g.
- What does the drug do with the patient: pharmacodynamics; e.g. binding to target and changing the
receptor

3

, ➔ Together they form rational pharmacotherapy

‘mechanism-based pharmacotherapy’ (=Rational pharmacotherapy) vs ‘evidence-based pharmacotherapy’ (= it
does not matter how it works, as long as it works, e.g. paracetamol)

Pharmacological phases in pharmacotherapy

Dosis

- Exposition phase: behaviour of a substance in the environment, changes in the application form,
available for uptake.
- Toxicokinetic phase: Absorption, distribution, biotransformation (toxification, detoxification),
excretion. ADME
- Toxicodynamic phase: Interactions with receptors or other (macro) molecules at the site of the
operation

Effect

DRUG-RECEPTOR-INTERACTIONS

Types of interactions

- Ligand-gated ion channels (ionotropic receptors
- G-protein-coupled receptors (metabotropic)
- Kinase-linked receptors
- Nuclear receptors
➔ Think of the type of rection you need when choosing pathway

Binding sites

- Receptors: agonist, antagonist
- Ion channels: blockers, modulators
- Enzymes: inhibitor, false substrate, pro-drug
- Transporters: normal transport, inhibitor, false substrate

Different types of binding: covalent, ionic, hydrogen, hydrophobic, van der waals

e.g. monarch butterfly is toxic to humans as the larvae sequester toxic steroids, known as cardenolides, from
milkweed → ouabain/digoxine also used as medicine → binds to the NA,K-ATPse receptor

RELATION CONCENTRATION – RECEPTOR OCCUPATION




4

Voordelen van het kopen van samenvattingen bij Stuvia op een rij:

Verzekerd van kwaliteit door reviews

Verzekerd van kwaliteit door reviews

Stuvia-klanten hebben meer dan 700.000 samenvattingen beoordeeld. Zo weet je zeker dat je de beste documenten koopt!

Snel en makkelijk kopen

Snel en makkelijk kopen

Je betaalt supersnel en eenmalig met iDeal, creditcard of Stuvia-tegoed voor de samenvatting. Zonder lidmaatschap.

Focus op de essentie

Focus op de essentie

Samenvattingen worden geschreven voor en door anderen. Daarom zijn de samenvattingen altijd betrouwbaar en actueel. Zo kom je snel tot de kern!

Veelgestelde vragen

Wat krijg ik als ik dit document koop?

Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.

Tevredenheidsgarantie: hoe werkt dat?

Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.

Van wie koop ik deze samenvatting?

Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper stellav19. Stuvia faciliteert de betaling aan de verkoper.

Zit ik meteen vast aan een abonnement?

Nee, je koopt alleen deze samenvatting voor €5,99. Je zit daarna nergens aan vast.

Is Stuvia te vertrouwen?

4,6 sterren op Google & Trustpilot (+1000 reviews)

Afgelopen 30 dagen zijn er 80364 samenvattingen verkocht

Opgericht in 2010, al 14 jaar dé plek om samenvattingen te kopen

Start met verkopen
€5,99
  • (0)
  Kopen