What’s New in the Lab-Part 1
David Baker
david.baker@qmul.ac.uk
Ideas of Today, Treatments of Tomorrow
What’s New in the Lab-Part 1
Ideas of Today, Treatments of Tomorrow
$1.5billion
10-14 years
Anonymous Thursday, June 12, 2014 6:52:00 pm
“If I was Prof G I'd tell Prof M that's he's got 3 years
to come up with the goods i.e. a cure or he'll be
signing on at the benefits office.”
www.ms-res.org
PHASE III
WORKS IN MSers
SAFE (& HINT OF WORING) IN MSers
?
PHASE I
SAFE IN HUMANS
PHASE II
IDEA
PHASE 0
SAFE IN ANIMALS
PROGRESSION-WHY DON’T WE HAVE DRUGS?
WE HAVE NO IDEAS
X
SIDE EFFECTS
Drugs Cause Harm
People Do Not Take Their Medicines
Effective Dose not Reached
SOLUTION: AVOID SIDE EFFECTS
Deliver Drugs to Where Needed
Inflammatory Penumbra
ACTIVE MS
Myelin (Brown Colour)
White Blood
Cells
Surrounding
Blood Vessel
Nerve Damage
BLOOD BRAIN BARRIER
BLOOD
CELL
MEMBRANE
DRUG
BRAIN
P GLYCOPROTEIN = DRUG PUMP
P-GLYCOPROTEIN (DRUG PUMP) IS SELECTIVELY
LOST FROM BLOOD VESSEL IN LESIONS
PERIVASCULAR LESION
White Blood cells
(Lesion)
Blood
Vessel
Without
Pump
Pump
on
Blood
vessel
P-GLYCOPROTEIN (DRUG PUMP) IS SELECTIVELY
LOST FROM BLOOD VESSEL IN LESIONS
Drug Pump Type I
Drug Pump Type 2
Abcb1 (P -glycoprotein)
Abcg2 (Breast Cancer Resistance Protein)
White blood cells= blue
Drug Pump = brown showing blood vessel wall
TARGETING THERAPY TO (LESIONS) WHERE IT IS NEEDED
Control Drug
New DRUG
BLOOD LEVELS
Activity on
P-glycoprotein
-ve
++++
Amount
BRAIN LEVELS
NEW DRUG
in
MS-Like
Disease
N-((5-(1-(2-(1H-imidazol-1-yl)ethyl)-1Hindazol-3-yl)-1,2,4-oxadiazol-3-yl)
methyl)benzamide
DETECTION LEVEL
TAKE PILL
Time (Hours)
TARGETING THERAPY TO (LESIONS) WHERE IT IS NEEDED
DRUG
CELLS
CELLS
DRUG
PUMP
CELLS
DRUG
SPINAL NERVE CONTENT
TARGETING THERAPY TO (LESIONS) WHERE IT IS NEEDED
Nerve
Loss
HEALTHY
NO-DISEASE
DMT
(LEMTRADA)
DISEASE
PLACEBO
DISEASE
NERVE PROTECTOR
(NEW DRUG)
SLOWS PROGRESSION
TARGETING THERAPY TO (LESIONS) WHERE IT IS NEEDED
WILL IT GET DEVELOPED?
OPTIC NEURITIS: PHENYTOIN TRIAL
PROXIMUS TRIAL: OXCARBAZEPINE TRIAL
SYMPTOM CONTROL-SPASTICITY
COGNITIVE
SIDE-EFFECTS
Drug
CNS
Side
Excluded Therapy Effect
BACLOFEN
CANNABIS
NO
NO
YES
YES
YES
YES
O
THERAPEUTIC
EFFECTS
VSN16R
YES
N
H
OH
N
Sensory Nerve
Sending information
of position of muscle
Spasticity –too excitement
causing Contractions
Movement Nerve
Controlling muscle
function
O
WHAT WOULD YOU WANT TO TAKE?
VSN16R & BACLOFEN
EFFECT (MUSCLE) RELAXED
VSN16R
(NO SIDE EFFECTS)
BACLOFEN
(SIDE EFFECTS)
Z Z
Z
Z
Z
CoI: Members of TeamG & UCLP are trying to commercially develop this drug
SAFE IN ANIMALS
2013
SAFE IN HUMANS
PHASE I
PHASE 0
PHASE II
2011
2002
2014
2005
2015
PHASE III
CoI: Members of TeamG & UCLP are trying to commercially develop this drug
REPURPOSING
IN THE LAB
WE & OTHERS
WE HAVE IDENTIFIED
LOTS OF EXISTING DRUGS
THAT MAY TARGET DIFFERENT
ASPECTS OF
NEURODEGENERATION
& REPAIR
THANKS FOR LISTENING