Lecture 2: 2/10
Therapeu(c modali(es
Types of therapeu.cs
- Several therapeu-cal modali-es available
- Spectrum becomes broader
- Conven-onal = all types of interven-on aimed at allevia-ng and eradica-ng the effects of
disease
o Improve disease symptoms and/or prognosis
o Alleviate effects of exis-ng disease
o Directed towards disease preven-on
o Achieve permanent cure
- Non-conven-onal
o Nutraceu-cals = range of dietary prepara-ons
§ slimming diets, diets with minerals, vitamins, fiber, an-oxidants, …
§ some scien-fic ra-onale
§ not subjected to formal regulatory approval
§ Ceu-cals are oGen not regulated. Sold you as products to help to lose weight, for
example
§ In the end you can’t be sure what the effect/benefit is of nutraceu-cals
§ Also safety is not sure
o Cosmeu-cals = cosme-cs supplemented with some ac-ve (?) substances
§ reduce skin wrinkles, promote hair growth, …
§ liNle or no scien-fic ra-onale
§ free sales (but major market !!)
§ Free sale -> major market -> lot of publicity
Current therapeu.cs
Conven&onal therapeu&c drugs
- Small molecules groups
o Most of current drugs (Pharmacopoeia)
o Chemicals
o Small molecular size -> important for the phamacokine-cs, oral uptake
o Small molecular drugs/en--es
o Advantages
§ Several targets -> also a disadvantage -> less specific, side/adverse effects
§ Accepted by profession and community
§ Various routes of administra-on
§ Longterm pharmaceu-cal experience
o Disadvantages
§ It becomes more difficult to find new small molecule drugs that differen-ate
them from others
§ Broader spectrum -> lower selec-vity -> toxicity
§ Pharmacokine-c limita-ons
, • Phase I clinical trial and you need a certain plasma concentra-on -> stop
with development or change the formula-on to increase the plasma
concentra-on (and efficacy)
§ Frequent poor oral absorp-on -> improve this by adding extra substances ->
vehicles are used for this (some of this vehicles are toxic by themselves)
- Natural products or semi-synthe-cally derived)
o an-bio-cs, an-cancer, opiates, sta-ns,
Biopharmaceu&cals
- = Noval therapeu-c modali-es
- = Non small molecule drugs
- Several groups
o Pep-de/protein mediators
o Blood cloZng factors
o Enzymes
o An-bodies (an-sera, an-toxins, mAb)
o Vaccines (inac-vated, aNenuated, subunit)
o Cells/-ssues (stem cells, graG- and transplant surgery)
- Advantages
o Higher selec-vity than small molecules drugs -> open new therapeu-cal op-ons
o More straigh]orward discovery
§ You really focus on the target and design it for the target -> less toxicity
o Unexpected toxicity is less common
o Higher product quality
- Disadvantages
o Much more expensive
o Lack of oral ac-vity and short half-life
o Designed for the human pharmacological target -> no good animal model
Beyond current biopharmaceu.cals …
Gene therapy
- Correc-ng gene-c defects by altering gene-c material of cells by recombinant DNA
technology
o Introduce new genes to replace missing or dysfunc-onal ones (virus vector: non-
integrated vs. integrated DNA)
o Aim at single-gene disorders (cys-c fibrosis, haemophilia) and cancer
o Restricted to soma-c cell treatments (ban on germ-cell gene therapy experiments
- Not many gene therapy products licensed yet for clinical use
- Disappoin-ng prospects (long-term safety, gene-delivery systems, …
- Become more and more important
- OGen a rare disease -> orphan drug
- Several ways of working with this
- Broad term: for example you are going to block the transcrip-on of the gene and later the
transla-on of the mRNA to the proteins
- An-sense DNA
o oligonucleo-de sequence complementary to part of a known mRNA sequence ->
selec-ve blocking of expression
o but:
Therapeu(c modali(es
Types of therapeu.cs
- Several therapeu-cal modali-es available
- Spectrum becomes broader
- Conven-onal = all types of interven-on aimed at allevia-ng and eradica-ng the effects of
disease
o Improve disease symptoms and/or prognosis
o Alleviate effects of exis-ng disease
o Directed towards disease preven-on
o Achieve permanent cure
- Non-conven-onal
o Nutraceu-cals = range of dietary prepara-ons
§ slimming diets, diets with minerals, vitamins, fiber, an-oxidants, …
§ some scien-fic ra-onale
§ not subjected to formal regulatory approval
§ Ceu-cals are oGen not regulated. Sold you as products to help to lose weight, for
example
§ In the end you can’t be sure what the effect/benefit is of nutraceu-cals
§ Also safety is not sure
o Cosmeu-cals = cosme-cs supplemented with some ac-ve (?) substances
§ reduce skin wrinkles, promote hair growth, …
§ liNle or no scien-fic ra-onale
§ free sales (but major market !!)
§ Free sale -> major market -> lot of publicity
Current therapeu.cs
Conven&onal therapeu&c drugs
- Small molecules groups
o Most of current drugs (Pharmacopoeia)
o Chemicals
o Small molecular size -> important for the phamacokine-cs, oral uptake
o Small molecular drugs/en--es
o Advantages
§ Several targets -> also a disadvantage -> less specific, side/adverse effects
§ Accepted by profession and community
§ Various routes of administra-on
§ Longterm pharmaceu-cal experience
o Disadvantages
§ It becomes more difficult to find new small molecule drugs that differen-ate
them from others
§ Broader spectrum -> lower selec-vity -> toxicity
§ Pharmacokine-c limita-ons
, • Phase I clinical trial and you need a certain plasma concentra-on -> stop
with development or change the formula-on to increase the plasma
concentra-on (and efficacy)
§ Frequent poor oral absorp-on -> improve this by adding extra substances ->
vehicles are used for this (some of this vehicles are toxic by themselves)
- Natural products or semi-synthe-cally derived)
o an-bio-cs, an-cancer, opiates, sta-ns,
Biopharmaceu&cals
- = Noval therapeu-c modali-es
- = Non small molecule drugs
- Several groups
o Pep-de/protein mediators
o Blood cloZng factors
o Enzymes
o An-bodies (an-sera, an-toxins, mAb)
o Vaccines (inac-vated, aNenuated, subunit)
o Cells/-ssues (stem cells, graG- and transplant surgery)
- Advantages
o Higher selec-vity than small molecules drugs -> open new therapeu-cal op-ons
o More straigh]orward discovery
§ You really focus on the target and design it for the target -> less toxicity
o Unexpected toxicity is less common
o Higher product quality
- Disadvantages
o Much more expensive
o Lack of oral ac-vity and short half-life
o Designed for the human pharmacological target -> no good animal model
Beyond current biopharmaceu.cals …
Gene therapy
- Correc-ng gene-c defects by altering gene-c material of cells by recombinant DNA
technology
o Introduce new genes to replace missing or dysfunc-onal ones (virus vector: non-
integrated vs. integrated DNA)
o Aim at single-gene disorders (cys-c fibrosis, haemophilia) and cancer
o Restricted to soma-c cell treatments (ban on germ-cell gene therapy experiments
- Not many gene therapy products licensed yet for clinical use
- Disappoin-ng prospects (long-term safety, gene-delivery systems, …
- Become more and more important
- OGen a rare disease -> orphan drug
- Several ways of working with this
- Broad term: for example you are going to block the transcrip-on of the gene and later the
transla-on of the mRNA to the proteins
- An-sense DNA
o oligonucleo-de sequence complementary to part of a known mRNA sequence ->
selec-ve blocking of expression
o but:
