The zebrafish (Danio rerio),
a new model system for proof of concept studies

Ard Peeters
Chardon Pharma
The Product
Chardon Pharma evaluates whether an idea or compound has therapeutic
potential. This is called obtaining proof...
POC can be obtained both in predictive animal models
and in small scale clinical studies. Performing these
studies is our ...
POC can be obtained both in predictive animal models
and in small scale clinical studies. Performing these
studies is our ...
POC can be obtained both in predictive animal models
and in small scale clinical studies. Performing these
studies is our ...
Characteristics of zebrafish
- Small, robust freshwater fish
- Easy to maintain, high fecundity (200 eggs / week)
Characteristics of zebrafish
-

Small, robust freshwater fish
Easy to maintain, high fecundity (200 eggs / week)
Most orga...
Characteristics of zebrafish
-

Small, robust freshwater fish
Easy to maintain, high fecundity (200 eggs / week)
Most orga...
Characteristics of zebrafish
-

Small, robust freshwater fish
Easy to maintain, high fecundity (200 eggs / week)
Most orga...
Advantages of zebrafish models
Costs
Rodent POC study:
Human POC study:
Danio POC study:

50 - 100 k€
500 – 10.000 k€
0,5 ...
Examples of Danio rerio research within Chardon Pharma

1. High throughput behavioral drug screening
2. Target finding for...
High throughput behavioral drug screening

Ethanol
High throughput behavioral drug screening

Pentylenetetrazole
High throughput behavioral drug screening

Buspirone
High throughput behavioral drug screening
Measuring blood brain barrier (BBB) penetration
5 dpf

Sibutramine
5 dpf: ED50 <...
Target finding for Chorea Huntington
Collaboration with EHDN

- Autosomal dominant neurological disorder
- CAG repeat in h...
Target finding for Chorea Huntington

No change

KO of potential
target
Behavioral observation
Huntingtin aggregation

Cha...
Target finding for Chorea Huntington

No change

KO of potential
target
Behavioral observation
Huntingtin aggregation

Cha...
Heart regeneration research
Funded by MIT; Collaboration with Duke university

- Heart attacks induce muscle damage and he...
Heart regeneration research

Yes

KO of potential
target

Heart regeneration ?
Induction of
heart failure

Assay developme...
Heart regeneration research

Yes

KO of potential
target

Heart regeneration ?
Induction of
heart failure

10 days

No
Screening of compounds for osteoporosis
Bone content = bone formation (osteoblasts) – bone degradation (osteoclasts)

Oste...
Screening of compounds for osteoporosis
New treatment option:

Osteoblast stimulators

Available testmodels:
1. Human oste...
Screening of compounds for osteoporosis
New treatment option:

Osteoblast stimulators

Available testmodels:
1. Human oste...
Screening of compounds for osteoporosis
New treatment option:

Osteoblast stimulators

Available testmodels:
1. Human oste...
Screening of compounds for osteoporosis
New treatment option:

Osteoblast stimulators

Available testmodels:
1. Human oste...
Screening of compounds for osteoporosis
PTH

BMP2A

Alendronate (bisphosphonate)
Screening of compounds for osteoporosis
table 1. Osteogenic effect of substances involved in the WNT-signaling pathway. Re...
Questions?

Ideas for collaboration?
Upcoming SlideShare
Loading in …5
×

SMB 24102013 Ard Peeters - ChardonPharma

730 views

Published on

Published in: Technology, Business
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
730
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
22
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

SMB 24102013 Ard Peeters - ChardonPharma

  1. 1. The zebrafish (Danio rerio), a new model system for proof of concept studies Ard Peeters Chardon Pharma
  2. 2. The Product Chardon Pharma evaluates whether an idea or compound has therapeutic potential. This is called obtaining proof of concept (POC). The Approach • We scout for new ideas that require proof of concept studies before they can be commercialized (scouting) • We invest intellectually in these ideas by bringing in our scientific and drug development expertise (consultancy). • We invest in these ideas financially via our business angels network (investment). • We perform the proof of concept studies (preclinical, phase I, phase IIA) (CRO). • We write and file patents for the ideas (patent application). • We bring the inventor in contact with an industrial partner (match making).
  3. 3. POC can be obtained both in predictive animal models and in small scale clinical studies. Performing these studies is our expertise.
  4. 4. POC can be obtained both in predictive animal models and in small scale clinical studies. Performing these studies is our expertise. A new model system is Danio rerio (the zebrafish)
  5. 5. POC can be obtained both in predictive animal models and in small scale clinical studies. Performing these studies is our expertise. A new model system is Danio rerio (the zebrafish)
  6. 6. Characteristics of zebrafish - Small, robust freshwater fish - Easy to maintain, high fecundity (200 eggs / week)
  7. 7. Characteristics of zebrafish - Small, robust freshwater fish Easy to maintain, high fecundity (200 eggs / week) Most organs fully functional between 3 – 5 dpf. Larvae are transparent
  8. 8. Characteristics of zebrafish - Small, robust freshwater fish Easy to maintain, high fecundity (200 eggs / week) Most organs fully functional between 3 – 5 dpf. Larvae are transparent Genome fully sequenced Genome, genetic pathways and development highly conserved between zebrafish and humans - Easy genetic manipulation
  9. 9. Characteristics of zebrafish - Small, robust freshwater fish Easy to maintain, high fecundity (200 eggs / week) Most organs fully functional between 3 – 5 dpf. Larvae are transparent Genome fully sequenced Genome, genetic pathways and development highly conserved between zebrafish and humans - Easy genetic manipulation - Large behavioral repertoire
  10. 10. Advantages of zebrafish models Costs Rodent POC study: Human POC study: Danio POC study: 50 - 100 k€ 500 – 10.000 k€ 0,5 – 5 k€ Timelines Rodent POC study: Human POC study Danio POC study: 1 – 12 months 6 – 24 months 1 – 5 days No DEC Challenge Acceptance of the models
  11. 11. Examples of Danio rerio research within Chardon Pharma 1. High throughput behavioral drug screening 2. Target finding for Chorea Huntington 3. Heart regeneration research 4. Screening of compounds for osteoporosis
  12. 12. High throughput behavioral drug screening Ethanol
  13. 13. High throughput behavioral drug screening Pentylenetetrazole
  14. 14. High throughput behavioral drug screening Buspirone
  15. 15. High throughput behavioral drug screening Measuring blood brain barrier (BBB) penetration 5 dpf Sibutramine 5 dpf: ED50 < 0,01mg/ml 12 dpf: ED50 > 0,1mg/ml 12 dpf
  16. 16. Target finding for Chorea Huntington Collaboration with EHDN - Autosomal dominant neurological disorder - CAG repeat in huntingtin gene - Huntingtin aggregates leading to neurodegeneration - Transgenic zebrafish model - Different CAG repeat in huntingtin gene - Huntingtin aggregates
  17. 17. Target finding for Chorea Huntington No change KO of potential target Behavioral observation Huntingtin aggregation Changed Danio with HD Assay development Drug screening Identified target
  18. 18. Target finding for Chorea Huntington No change KO of potential target Behavioral observation Huntingtin aggregation Changed Danio with HD 10 days
  19. 19. Heart regeneration research Funded by MIT; Collaboration with Duke university - Heart attacks induce muscle damage and heart failure - Human heart muscle cannot regenerate - Zebrafish heart muscle has regenerative capacity.
  20. 20. Heart regeneration research Yes KO of potential target Heart regeneration ? Induction of heart failure Assay development Drug screening Potential causal factor No
  21. 21. Heart regeneration research Yes KO of potential target Heart regeneration ? Induction of heart failure 10 days No
  22. 22. Screening of compounds for osteoporosis Bone content = bone formation (osteoblasts) – bone degradation (osteoclasts) Osteoporosis: Bone content ↓ = bone formation ↓ – bone degradation ↑ Osteoporosis treatment Bone content ↓ = bone formation ↓ – bone degradation ↑
  23. 23. Screening of compounds for osteoporosis New treatment option: Osteoblast stimulators Available testmodels: 1. Human osteoblast culture (no interaction with osteoclasts) 2. Rodent model (invasive, time consuming, costly)
  24. 24. Screening of compounds for osteoporosis New treatment option: Osteoblast stimulators Available testmodels: 1. Human osteoblast culture (no interaction with osteoclasts) 2. Rodent model (invasive, time consuming, costly) The alternative Danio rerio
  25. 25. Screening of compounds for osteoporosis New treatment option: Osteoblast stimulators Available testmodels: 1. Human osteoblast culture (no interaction with osteoclasts) 2. Rodent model (invasive, time consuming, costly) The alternative Danio rerio
  26. 26. Screening of compounds for osteoporosis New treatment option: Osteoblast stimulators Available testmodels: 1. Human osteoblast culture (no interaction with osteoclasts) 2. Rodent model (invasive, time consuming, costly) The alternative Danio rerio
  27. 27. Screening of compounds for osteoporosis PTH BMP2A Alendronate (bisphosphonate)
  28. 28. Screening of compounds for osteoporosis table 1. Osteogenic effect of substances involved in the WNT-signaling pathway. Red arrows indicates a negative effect (4 decreases or 3 decreases and one neutral effect). Green arrows indicate a positive effect (4 increases or 3 increases and one neutral effect). Compound name effect Compound name effect Compound name effect foxy-5 1,04 Box5 1,07 CCT036477 anandamide 0,78 TNP-470 0,86 Busutinib QS-11 0,93 IWR-1 1,15 Carnosol diarylsulfonesulfonamide 0,19 XAV939 0,88 Favanone IQ1 1,17 IWP-2 0,90 Retinoic acid SB-216763 0,71 Bafilomycin A1 0,81 Pterostilbene BIO 0,93 Sulindac Sulfide 1,28 Hexachlorophene TWS-119 0,62 Celecoxib 1,58 DHA CHIR99021 1,08 Diclofenac.Na 1,20 EPA IM-12 1,00 Niclosamide 1,56 JS-K AR-A014418 1,17 ICG-001 0,66 Pyrvinium pamoate kenpaullone 0,77 Harmine.HCl 0,44 Apigenin sodium valprolate 0,58 Curcumin 0,85 Ellagic acid dihydrate BML-284 0,77 PNU-74654 0,80 D4476 Deoxycholic acid 0,76 Quercetin 0,68 Trichostatin A Reservatrol 0,91 BML285 0,52 5-Aza-2-deoxycytidine PGE2 0,87 NO-ASA 0,64 Thalomide WAY-262611 0,92 FH-535 0,71 Genistein Purpurogallin 0,85 Val-Val-Val 0,75 PP2 Exifone 0,79 BML286 0,95 NCI16221 Gallic acid 0,65 Sulindac 1,62 Doxorubicin.HCL Riluzole 1,42 EGCG 0,73 3253-5986 LY456236.HCL 0,53 imatinib mesylate 1,01 Usnic Acid (-)-Terreic acid 0,80 Troglitazone 0,64 Forskolin 0,77 Rosiglitazone maleate 0,92 0,96 0,72 0,94 0,96 0,95 0,81 0,82 0,61 0,99 1,13 0,91 1,38 1,29 0,60 0,31 1,20 1,51 1,39 1,35 0,75 0,25 1,25 0,99
  29. 29. Questions? Ideas for collaboration?

×