Matthew Campbell Ocular Genetics Unit, TCD Neuronal barrier modulation: a new technology for preservation of vision
The Problem <ul><li>98% of drugs with established potential for treating neurological diseases do not easily diffuse acros...
 
Claudin-5 <ul><li>23 kDa tight junction protein </li></ul><ul><li>In 2003, claudin-5 knockout mice were reported to show a...
<ul><li>Retinal Disease Models </li></ul><ul><li>Age-Related Macular degeneration (AMD): Major sight threatening disease i...
 
 
 
Permeability experiments using Gadolinium-diethyenetriamine-penta-acetic acid injection  Magnetic Resonance Imaging (MRI) ...
Ocular drug delivery by barrier modulation
 
Laser induced Choroidal neovascularisation (CNV) Administered Doxycycline in drinking water for 2 weeks while receiving 2 ...
“ The rationale was not to develop an RNAi therapeutic agent per se, but to use RNAi to allow the application of conventio...
<ul><li>Traumatic brain injury and cerebral edema </li></ul><ul><li>There has been little change in the treatment of acute...
 
 
Volume rendering of TBIs Cold-induced edema of the visual neocortex in mice – a model of TBI (high resolution T2 imaging)
NT siRNA CLDN5 siRNA 24 hr 48 hr 72 hr
<ul><li>Treated animals show reduced brain swelling and display significant </li></ul><ul><li>Cognitive improvement over u...
Glioblastoma Multiforme (GBM):  Grade IV brain tumour <ul><li>About 25,000 new cases of GBM diagnosed each year in Europe ...
 
 
 
Induced permeability of the blood-tumour barrier
The Ocular Genetics Unit at TCD Prof. Pete Humphries Dr. Marian Humphries Dr. Anna-Sophia Kiang Dr. Paul Kenna Prof Jane F...
Upcoming SlideShare
Loading in …5
×

Dr Matthew Campbell - AGM 2011 - AMD Drug Delivery

1,097 views

Published on

Dr Matthew Campbell (TCD) explains the latest developments out of the Trinity lab in the development of new drug therapies to treat Age-related Macular Degeneration.

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,097
On SlideShare
0
From Embeds
0
Number of Embeds
104
Actions
Shares
0
Downloads
3
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Dr Matthew Campbell - AGM 2011 - AMD Drug Delivery

  1. 1. Matthew Campbell Ocular Genetics Unit, TCD Neuronal barrier modulation: a new technology for preservation of vision
  2. 2. The Problem <ul><li>98% of drugs with established potential for treating neurological diseases do not easily diffuse across the BBB or iBRB. Systemic delivery of such compounds is either impractical or highly inefficient. </li></ul><ul><li>Neuronal edema induced by out-of-hospital cardiac arrest, stroke or traumatic brain injury is massively common and often involves severe visual impairment. Current treatments for neuronal edema are rudimentary, very often ineffective and have not changed in over 80 years </li></ul>
  3. 4. Claudin-5 <ul><li>23 kDa tight junction protein </li></ul><ul><li>In 2003, claudin-5 knockout mice were reported to show a size-selective BBB to molecules below 800 Daltons </li></ul>
  4. 5. <ul><li>Retinal Disease Models </li></ul><ul><li>Age-Related Macular degeneration (AMD): Major sight threatening disease in developed countries </li></ul><ul><li>Current therapies are limited and invasive- Direct and regular intraocular injection of antibodies targeting VEGF. No end-point has been established for treatment. </li></ul>
  5. 9. Permeability experiments using Gadolinium-diethyenetriamine-penta-acetic acid injection Magnetic Resonance Imaging (MRI) Gd-DTPA has a MW of 742 Daltons
  6. 10. Ocular drug delivery by barrier modulation
  7. 12. Laser induced Choroidal neovascularisation (CNV) Administered Doxycycline in drinking water for 2 weeks while receiving 2 I.P injections of VEGF receptor antagonist Sunitinib malate (532 Da)
  8. 13. “ The rationale was not to develop an RNAi therapeutic agent per se, but to use RNAi to allow the application of conventional drugs for treating diseases of the brain, CNS or eye”. [Professor John Rossi, commenting on the technology of Neuronal Barrier Modulation, EMBO Molecular Medicine, 2011]
  9. 14. <ul><li>Traumatic brain injury and cerebral edema </li></ul><ul><li>There has been little change in the treatment of acute brain swelling over the past 80 years. </li></ul><ul><li>In Europe alone, brain injuries cause over 66,000 deaths while almost 1.6 million people are admitted to hospital each year </li></ul><ul><li>More people suffer a traumatic brain injury (TBI) each year than the numbers diagnosed with breast, lung, prostate, brain, and colon cancer combined. These injuries can severely impact on visual function. </li></ul>
  10. 17. Volume rendering of TBIs Cold-induced edema of the visual neocortex in mice – a model of TBI (high resolution T2 imaging)
  11. 18. NT siRNA CLDN5 siRNA 24 hr 48 hr 72 hr
  12. 19. <ul><li>Treated animals show reduced brain swelling and display significant </li></ul><ul><li>Cognitive improvement over untreated animals. </li></ul><ul><li>A highly effective therapeutic for neuronal edema induced by TBI/ </li></ul><ul><li>Cardiac arrest </li></ul>
  13. 20. Glioblastoma Multiforme (GBM): Grade IV brain tumour <ul><li>About 25,000 new cases of GBM diagnosed each year in Europe and North America combined. </li></ul><ul><li>Commonly presents with symptoms of vision aberration. Prognosis for malignant GBM is extremely poor. </li></ul><ul><li>Mean survival of 20 weeks by surgical re-sectioning and 36 weeks by combined surgery and radiation, the inclusion of chemotherapy offering only minimal survival advantage, raising median survival to 40-50 weeks. </li></ul><ul><li>Major problem is the BBB and BTB – drugs can not get across. </li></ul>
  14. 24. Induced permeability of the blood-tumour barrier
  15. 25. The Ocular Genetics Unit at TCD Prof. Pete Humphries Dr. Marian Humphries Dr. Anna-Sophia Kiang Dr. Paul Kenna Prof Jane Farrar Ms Anh Nguyen Mr Finnian Hanrahan Mr James Keaney Ms Ema Ozaki

×