Mechanism and Therapy

Partnering Event
Session:
Mechanisms and Therapy,
including cell therapy
CHARLES S. IRVING
Charles S. Irving, PhD, CEO
+972-54-524-5677
[email protected]
Topic: Mechanisms and therapies, including cell therapy
Subject of interest:
Therapeutic cells derived from human embryonic stem cell (hESC) for the
treatment of neural and retinal degenerative diseases
Core Technology:
• Methods for neural and retinal cell differentiation and transplantation
• Translation of research methods to cGMP production
• Use of clinical grade hESCs as starting material
• Cell characterization and animal models
• Safety testing of hESC derived cells
No existing Israel – Canada partnerships yet
Cell Cure Neurosciences
Team:
CSO :
Prof. Benjamin Reubinoff, Head of hESC Research Center, Hadassah
Consultants:
Prof. Tamir Ben Hur, Head Neurology, Hadassah
Prof. Eyal Banin, Head Macular Degeneration Group, Hadassah
Company Core Team working with Hadassah experts
Accomplishments:
- Mid-brain dopaminergic neural progenitor cells for Parkinson’s disease
- Oligodendrocyte progenitor cells for demyelinating diseases•
- Retinal pigmented epithelium (RPE) cells for dry age-related macular degeneration•
- License Option Agreement with Teva for OpRegen®
Modes and Areas of Collaborations:
- Consortiums, tech transfers (NDAs, MTAs, licenses)
- Disease targets and platform technologies
cell lines and purification methods, scaffolds, devices of delivery, assays of
biodistribution
microfluidic systems for point-of-care cell concentration and resuspension
ADRIAN HAREL
BrainStorm Cell Therapeutics Ltd.
12 Bazel St., POB 10019 Kiryat Aryeh, Petach Tikva, Israel 49001
Tel: (972) 3.923.6384, Fax: (972) 3.923.6385
E-mail: [email protected]
Web: www.brainstorm-cell.com

Stem Cell Therapy for ALS

NurOwn ™ autologous adult stem cells
transplanted into patients

Major accomplishments:

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Brainstorm was granted FDA orphan drug designation for
NurOwn™ as a candidate stem cell therapy for ALS.
Brainstorm obtained Israeli Ministry of Health clearance for a
clinical trial for its differentiated stem cell therapy.
Phase I/II trial for treatment of ALS initiated the at the Hadassah
University Medical Center, Jerusalem in June 2011.
No existing partnership between Brainstorm and
Canada
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NurOwn™ Therapy Step by Step
Stem cells are harvested from the Bone marrow, and Mesenchymal Stromal cells
(MSC) isolated from the total bone marrow population and then expanded and
induced to differentiate into MSC-NTF cells. The cells are then transplanted back
into the patient at the site of damage (into the brain for Parkinson’s disease, the
muscles or Spinal cord for ALS and Spinal cord Injury).
7
Proposed Research Projects
 Animal model for motor-neuron degeneration
Development of new animal models for neuron degeneration allowing
to investigate the effect of stem cell transplantation
 Production process in Serum-Free Medium
Development of a production process based on Serum-Free Medium
(SFM) devoid of human-derived components, suitable for use in any
worldwide location in which BrainStorm may wish to establish its
production process.
 Neuroprotection cell-based assays
Development of functional in-vitro cell based assays in which
Neuroprotection of Brainstorm’s NTF secreting cells can be evaluated.
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MICHAEL G. FEHLINGS
Name: Michael G. Fehlings MD PhD; University of Toronto Neuroscience Program
Contact: Tel: 416-603-5072; email: [email protected]
•
•
•
•
Topic: Mechanisms and Therapy (Cell therapy)
Subject of interest: Neural stem cells as a strategy for remyelination of CNS
white matter injury/disease
Core technology: Neural stem cells; non-viral induced pluripotent stem cells
About the group and major accomplishments:
– Collaborations with NeuroDevNet NCE
– Multidisciplinary SCI-NET team which is focused on combining neural stem cells,
bioengineered strategies and neurosurgical strategies for the treatment of brain and spinal
cord injury (team is led by Michael Fehlings and includes Derek van der Kooy, Molly Shoichet,
Andras Nagy, Cindi Morshead, Charles Tator)
•
Existing partnership between Israel and Canada– Some initial linkages with Michal Schwartz (Weitzman Institute)
•
Suggestions for mode of collaboration (for example consortium)– Opportunities for collaboration through NeuroDevNet NCE
– Through Ontario Brain Institute/University of Toronto Neuroscience Program
Schematic of Fibroblast to Axonal Remyelination:
The Promise of Induced Pluripotent Stem Cells
iPS cell
FRIDA GRYNSPAN
Mechanisms and Therapy, including cell therapy
Subject of Interest: Development of Cell-based Therapeutics.
About the Company: Pluristem Therapeutics Inc. is a leading developer of placentabased cell therapies. The company owns a patented PLX (PLacental eXpanded) cells drug
delivery platform. Pluristem has a strong patent portfolio, GMP certified manufacturing and
research facilities, strategic relationships with major research institutions and a seasoned
management team. The R&D team include 10 PhD and 2 MD covering the fields of
cellular therapy, immunology , and angiogenesis.
Core technology: The company has developed and owns a unique cell manufacturing
technology. The cell product(s) release a cocktail of therapeutic proteins in response to a
host of local and systemic ischemic and inflammatory signals. PLX cells are grown using the
company’s proprietary 3D micro-environmental technology and are an off-the-shelf product
that requires no tissue matching prior to administration.
Major accomplishments: PLX-PAD, has successfully completed 2
dose escalation
Phase I clinical trials totaling 27 patients suffering from critical limb ischemia (CLI) in
Germany and the USA. The product was found to be safe and potentially effective for the
treatment of end stage peripheral artery disease.
Major Accomplishments cont.:
Pluristem received an approval for its pivotal Phase II/III study in critical limb ischemia (CLI)
from both the EMEA and the FDA.
Pluristem and the Berlin-Brandenburg Center for Regenerative Therapies (BCRT), in
cooperation with the Charité - University of Medicine in Berlin, announced the results of a
preclinical study demonstrating significant improvement in the recovery of muscle function,
when compared to controls, following the local administration of PLX cells in a muscle injury
mice model.
Pluristem's has entered into an exclusive out-license agreement with United Therapeutics
Corporation (NasdaqGS: UTHR) for the use of Pluristem’s PLX to develop and
commercialize a cell-based product for the treatment of Pulmonary Hypertension (PH).
Pre-clinical animal models have demonstrated PLX cells are also potentially effective in
nerve pain, when administered locally, and in inflammatory bowel disease, MS and stroke,
when administered systemically. Furthermore we are currently studying the effect of iv
infusion of PLX cells on the BM after exposure to semi lethal doses of radiation.
Possible modes of collaboration The Company is interested in exploring through
collaborative efforts additional indications including, but not limited to, MS, Parkinson and
Alzheimer’s disease. The aim of the Company is to check the therapeutic effect of the cells
at the basic research and preclinical levels as to develop clinically relevant programs that will
lead to clinical trials in the after mentioned indications.
SHULAMIT LEVENBERG
Prof. Shulamit Levenberg Tissue Engineering Lab
Technion- Israel Institute of Technology, Department of Biomedical Engineering
+972(4)8294810; [email protected]
• TOPIC: Mechanisms and Therapy, including cell therapy
• SUBJECT OF INTEREST: Tissue Engineering Strategies for Spinal Cord Repair
Aims:
1) Develop a clinically relevant implantable construct using cells seeded on a biodegradable
scaffold;
2) Test the ability of this construct to promote neural regeneration and functional recovery
following implantation into a mouse model of spinal cord injury.
• CORE TECHNOLOGY: Vascularization of engineered tissues; Stem cell differentiation on 3D
scaffolds; Controlling stem cell microenvironments
Lesman. et al, Submitted, 2011
Levy et al .Tissue Eng. 2009
Levenberg, et al Blood 2007,
Levenberg et al , J. Vascular Res, 2005
Levenberg et al, Nat Biotech, 2005
Caspi et al . Circ Res, 2007
Lesman et al. Tissue Eng 2010
Lesman et al. Ann N Y A S. 2010
Lesman et al. Biotech Bioeng,
2010
Olfactory bulb cells grown on PLLA/PLGA scaffolds
p75NTR
Phalloidin
Heart Muscle
scaffold
Merged
X 1.6
Confocal Imaging of Vascularization
Network on PLLA/PLGA Scaffold and its
integartion with the host vasculature
EXISTING PARTNERSHIP BETWEEN ISRAEL AND CANADA: Prof. Charles
Tator (Toronto Western Research Institute, Canada), a world leader in spinal
cord regeneration with extensive experience in experimental SCI models,
stem cell transplantation, and spinal cord ischemia. He has over 270 peerreviewed articles, and many prestigious awards.
•
SUGGESTIONS FOR MODE OF COLLABORATION: Development and
characterization of the cellular construct will be performed in Prof.
Levenberg’s lab. The potential of the cellular construct to promote
functional neural regeneration will be tested in animal models in
collaboration with other groups.
Nature Biotech, 2005, Circulation Res. 2007
Tissue Eng. Rev. 2009, Tissue Eng. 2010, Ann NY Acad Sci. 2010
ARIE DAGAN
REUVEN OR
Dr. Arie Dagan [email protected]
052-2462593
Prof. Reuven Or [email protected] 02-6776561
Topic: Cell therapy
Subject of interest:
Core technology: We develop an innovative homogenic culture of human
neural cell lines derived from UCB by adding our novel synthetic
sphingolipid analogues combined with differentiation and proliferation
factors at different developmental stages of cell differentiation.
The Bone Marrow Transplantation Department at Hadassah Hebrew University Medical
Center operates as a national center for bone marrow transplantation and stem-cell-based
medicine.
* The department uses stem cells from various sources including bone marrow, peripheral
blood, umbilical cord blood and the placenta.
* The department treats patients of all ages who are in need of bone marrow
transplantation. Treatment is provided within an integrated setting including both inpatient
and ambulatory treatment centers.
* The department includes a laboratory complex which is affiliated with the Hebrew
University’s School of Medicine.
* The laboratory's team, headed by Prof. Reuven Or, includes a number of highly
respected and accomplished scientists who conduct advanced research with a focus on
biological mechanisms of stem cells derived from cord blood and bone marrow.
The biochemistry laboratory at the Hebrew University specializes in the development of
novel synthetic sphingolipid analogues for manipulation of sphingolipid metabolism and cell
regulation. We are developing inhibitors of enzymes participating in the sphingolipid
cascade as novel agents in cancer chemotherapy. Another research focuses on
sphingolipid signaling, in particular Ceramide and Sphingosine-1-Phosphate, in the acute
pathophysiology of CNS injury, neurodegenerative diseases and repair mechanisms.
GFAPFITC
MAP2FITC
Staining of Neuronal markers in human
neural cell line derived from umbilical
cord blood
PHILIP LAZAROVICI
HADAR ARIEN-ZAKAY
The Hebrew University of Jerusalem
Institute for Drug Research, School of Pharmacy
Laboratory of NeuroPharmacology
Prof. Philip Lazarovici,
[email protected], 972-2-6758729
Dr. Hadar Arien-Zakay,
Laboratory of Brain Trauma
Prof. Esther Shohami
[email protected],
972-2-6757513
Sheba Medical Center
Division of Hemathology,
BMT&CBB
Prof. Arnon Nagler
[email protected]
972-3-5305830
[email protected], 972-2-6757767
Topic - Mechanisms and Therapy, including cell therapy
Subject of interest – Mechanisms of stem cells therapeutic effect in brain ischemia
Core technology – Stem cells, ischemic and neuroprotection in vitro and in vivo
validated pharmacological models
About the group and major accomplishments –
** Accelerating drug discovery towards licensing in neurology and regenerative
medicine.
** Unique expertise in molecular pharmacology of growth factors and stem cells for
novel lead compounds and cell therapy.
** Over 20 years of pharmacological contracts with companies including Fidia Italy;
USA: McNeil Pharmaceutical, Promega; Japan: Kyowa Hakko Kogyo; Israel: Alomone
Labs, Sigma, Compugene, D-Pharm, Given Imaging, Teva, Rafa, Pluristem.
Existing partnership between Israel and Canada – Prof. David Kaplan and
Prof. Freda Miller, Hospital for Sick Children MaRs Center, University of
Toronto, Toronto; Prof. Uri Saragovi, Dep. Pharmacology, McGill University, Montreal
Suggestions for mode of collaboration – contract services, licensing, consortium (Yissum)
Regenerative medicine: mechanisms of stem cell therapeutic effects
Delivery
systems
Tissue engineered scaffolds
for brain implantation
Non-invasive far near
infra-red imaging
Proteomics and
immune assays
Traumatic ischemic brain injury mice model (wild type, transgenic and knock out)
Neurovascular ischemic pharmacological models in vitro (OGD)
(Primary, cloned and stem cell derived cortical, sensory and sympathetic neurons,
Brain capillary endothelium, Transformed neuronal and glial cells)
Neurotrophins
(NGF, BDNF, GDNF)
Angiogenic growth factors
(VEGF, FGF-2)
Antioxidants
(Glutathione, Carnosine,
Homocarnosine)
Human cord blood and derived neuroprotective progenitors
Adult skin neuronal stem cells
ERAN PERLSON
Molecular Mechanisms of
Axonal Transportand of Neurodegeneration
Eran Perlson,
TAU Medical School
Department of Physiology and Pharmacology
• Alterations in axonal transport leads to neurodegenerative diseases
• Dynein play a role both in long distance signaling and in receptors
clustering and targeting for example in the neuromuscular junction
In vitro microfluidic platform with motor
neuron cell bodies on one side and muscle
cells on the other, creates a powerful
system to study axonal transport and
neuromuscular junction maintenance
mechanisms
Knowledge /
Control over
Components
Complexity
From in vitro to In vivo model systems
Our current efforts are focused on studying molecular mechanisms of:
•
Axonal transport
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Communication between the neuron and its environments
•
Retrograde signaling and cell survival
•
Synapse stability and maintenance
•
RNA transport in health and disease
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Receptors spatial targeting
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Virus trafficking
•
Membrane dynamics
•
Microfluidic system, single molecule and nanotechnology
TONY CRUZ
Tony Cruz
Transition Therapeutics Inc.
416-260-7770, [email protected]
• Topic: Mechanisms and Therapy
• Subject of Interest: CNS drug development
• About Transition
– Clinical and preclinical stage drug candidates in CNS, inflammatory and
metabolic indications
– Expertise in advancing preclinical drug candidates to the clinic
– Expertise in clinical trials in Alzheimer’s disease, multiple sclerosis,
traumatic brain injury and other non-CNS indications
– Strategic partnerships with large pharma (Elan and Eli Lilly)
– Listed on NASDAQ (TTHI) and TSX (TTH)
• Leveraging resources and expertise between Israel and Canada for
novel CNS drug development
LEVERAGE OF RESOURCES AND EXPERTISE BETWEEN ISRAEL AND CANADA
FOR NOVEL CNS DRUG DEVELOPMENT
1. Establish a system to evaluate and rapidly fund innovation with clear and short-term goals to
validate technology towards product development and partnerships
2. Identify expertise and/or third party businesses in both countries to take on the design and
execution of drug development, including manufacturing, preclinical and clinical studies for
individual projects
3. Identify expertise and /or third party businesses in both countries to take on the design and
execution of the development of devices and diagnostics
4. In order to fund development of these projects, establish clear guidelines and criteria to rapidly
fund innovative projects:
• Evaluation team for each area
• Team to develop strategy/plan to proof of concept or value creation point that meets
all industry standards
• Develop a business strategy and timelines for program to advance, recruit investment
and potential partnerships
• Develop a competitive analysis for the program and criteria for development to meet
market needs
• Team to evaluate progress and discontinue funding if criteria are not met or changes
in competitive environment no longer makes the investment worthy.
5. Establish a fund or budget for funding innovation alone or in partnership with industry/investors
MALKA COHEN-ARMON
ILANA GOZES
Tel-Aviv University
PI: Prof. M. Cohen-Armon, D.Sc.
Dept. of Physiology & Pharmacology and Neufeld Cardiac Research Institute,
Sackler School of Medicine, [email protected]
Co-PI: Prof. I. Gozes. Ph.D.
Dept. of Human Molecular Genetics and Biochemistry, Sackler School of Medicine,
Editor-in-Chief, Journal of Molecular Neuroscience and Chief Scientific Officer Allon
Therapeutics Inc. www.allontherapeutics.com
Topic: Mechanisms and Therapy, including cell therapy
Subjects of Interest: Molecular mechanisms underlying long-term memory formation
Exclusive erasure of memories by PARP inhibitors (frightening
or compulsive memories)
Core technology:
Biochemical pharmacological and cell biology methods.
Signal transduction mechanisms targeting gene expression
PARP proteins and chromatin remodeling
Collaboration with Inotek Inc., MA, USA.
Major accomplishments: Discovery of signal transduction mechanisms
underlying long-term memory formation
Relevant references
• Long-term memory requires polyADP-ribosylation. Cohen-Armon et al., Science
2004, 304: 1820-1823
• PolyADP-ribosylation is involved in neurotrophic activity. Visochek et al., J. Neurosci.
2005, 25:7420-7428.
• DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity:
A link to histone acetylation. Cohen-Armon et al., Mol. Cell 2007, 25: 297-308
• PARP-1 activation in the ERK signaling pathway. Cohen-Armon M., Trends In
Pharmacol. Sci. 2007, 28: 556-560
• PolyADP-ribosylation is required for long-term memory formation in mammals.
Goldberg et al. J. Neurochem. 2009, 111:72-79
Existing partnership between Israel and Canada: None
Suggestions for mode of collaboration: Consortium
DANIEL GOLDOWITZ
Name: Daniel Goldowitz
NeuroDevNet, Centre for Molecular Medicine and Therapeutics, Children
Family Research Inst., Dept Medical Genetics, UBC
Contact: 604-875-3822, [email protected]
• Topic: Mechanisms and Therapy, including cell therapy
• Brain Development
• Animal models, gene expression, clinical studies in Autism, Cerebral Palsy,
and Fetal Alcohol Spectrum Disorder
• NeuroDevNet is the first trans-Canadian Network that is focused on Brain
Development
• Ilan Golani, Nissim Ben-Arie, Michal Begin
• There are excellent researchers and potential companies engaged in issues
related to brain development that could be catalyzed toward action
through this initial meeting.
EREZ LEVANON
•
Mechanisms and Therapy, including cell therapy
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•
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Subject of interest : RNA editing in the brain
Core technology: global screen for RNA editing
About the group and major accomplishments:
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3 postdocs, 4 PhD Students
Large scale Identification of editing in human (Levanon at el, Nature
biotechnology 2004)
Genomic screen for editing sites (Li*, Levanon* at el ;Science 2009)
Editing in primate (Paz, Levanon at el ; PNAS 2010)
Editing in aging (Nicholas at el Mech Ageing Dev. 2010)
Existing partnership between Israel and Canadna -none
Suggestions for mode of collaboration: -consortium?…
A to I RNA editing
•
RNA editing is a post-transcriptional
change in the RNA sequence
Adenosine is converted by ADAR protain into
inosine- and read as Guanosine.
• RNA editing is essential,
Altered editing patterns were found in brain
related diseases.
• Editing lead to complexity of the
human brain transcriptome
• A-to-I RNA editing is common in
human and usually primate specific
Glutamate receptor
Serotonin receptor
Screen for RNA editing by padlock
Target Capturing technology
pol
lig
feature 1
feature 2
PCR
Illumina)
Li*, Levanon* et al . Science 2009
Editing examples
E>G
Ca2+-dependent secretion activator (CADPS)
Editing rescues a
stop codon (UAG)
into tryptophan
(UGG).
Adding 29 amino
acids to the protein
amyloid beta A4 precursor protein-binding
MOSHE SZYF
Name: Moshe Szyf McGill University Montreal Canada
Contact: 514-398-7107 [email protected]
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Topic: Mechanism and Therapy
Subject of interest: Epigenetic therapeutics in mental health
Core technology: Epigenetics pharmacology and biochemistry
About the group and major accomplishments: Discovery of behavioral
epigenetics and discovery of DNA methylation as a therapeutic target and
developing of DNA methylation pharmacology
• Existing partnership between Israel and Canada; to be determined.
• Suggestions for mode of collaboration: pharmaceutical spinoff
collaboration for developing epigenetic drugs for mental health
Epigenetic pharmacology reverses epigenetic programming of
behavior
MICHAEL S. KOBOR
Name: Michael S. Kobor
Centre for Molecular Medicine and Therapeutics, Child and Family Research
Institute, Department of Medical Genetics, University of British Columbia
NeuroDevNet NCE & AllerGen NCE; Scholar Canadian Institute for Advanced
Research
Contact: 604 875-‐3803; [email protected]
•
•
Topic: Mechanisms and Therapy, including cell therapy
Subject: Epigenetics in human health and disease
–
–
•
•
Core technology: High throughput quantitative measurements for epigenetic
Major accomplishments:
–
–
–
–
–
•
•
Fetal alcohol syndrome, early brain and biological development,
neurodegenerative disorder, healthy aging and age‐related diseases
Discovery two key enzymes involved in epigenetic regulation and gene expression
Revealed mechanisms for early-‐life environments such as poverty and
parental stress “get under the skin” to affect health across life-‐span
Established with Michael Hayden and Max Cynader the “Genetics and
Epigenetics Centre” of the Canadian Longitudinal Study of Aging
Existing partnership between Israel and Canada: None as of yet
Suggestions for mode of collaboration: Israel-‐Canada consortium for
population and disease cohorts with joint and coordinated measures,
interfacing with companies focused on technology development and
biomarker discovery
GERSHON GOLOMB
Gershon Golomb
School of Pharmacy, Faculty of Medicine,
The Hebrew University of Jerusalem
[email protected]
http://research.ekmd.huji.ac.il/researchers.asp?id=268#page_211
Topic: “Mechanisms and Therapy, including cell therapy”
Canadian Collaborators
M. Griffith, Ottawa Eye Institute, Ottawa Hosp.
F. Gu, Institute of Nanotechnology, U. Waterloo
Ongoing Research Topics
• Anti-inflammatory
effects
by
nanoparticles
of
bisphosphonates.
• Nanoparticles of antisense and siRNA in mammary
carcinoma.
• Immunomodulation by nanoparticles.
• Targeted nanoparticles in cancer therapy.
50 nm
100 nm
BBB Transport by Nanoparticles Exploiting
the Innate - Immunity System (TransBrain)
• The brain is under immunological surveillance
– Increased BBB passage of monocytes/neutrophils
• brain-associated inflammatory disorders (multiple
sclerosis, Alzheimer's disease, Cancer, TBI and more)
• Specific liposomes and polymeric NP are
phagocytized by circulating monocytes
– discharge their encapsulated drug in the brain
tissues.
ILLANA GOZES
•
•
•
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•
Topic: Mechanisms and Therapy
Subject of interest: Neuroprotection, nerve cell skeleton and
transport system, learning, memory, motor function,
neurodevelopment, neurodegenerative and neuropsychiatric
diseases
Core technology: Neuroprotective proteins
About the group and major accomplishments: Discovery of
neuroportective genes and drug candidates preclinical
discovery team (TAU)– davunetide in phase II/III clinical trials in
progressive supranuclear Palsy (PSP), a Parkinson-like
syndrome (Allon)
Existing partnership Israel and Canada: TAU (Ramot) and Allon.
Suggestions for mode of collaboration: Consortium - TAU Center for
Neurodevelopment, Neurodegeneration, Neuroprotection:
deciphering mechanisms + cell/animal/ high throughput and
proof of concept testing facilities concentrating on
Israeli/Canadian innovations.
Fundamental Mechanism of Action
Microtubules
Essential for neuronal structure and function
Neurodegeneration
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Destabilization and breakdown of
microtubules
Progressive loss of function
Tau hyperphosphrylation
Leads to cell death
Neuroprotection

Recent reviews
Gozes et al., Curr Alzheimer Res. 2009; 6:455-60.
Morimoto et al., Chimica Oggi / Chemistry Today. 2009; 27: 16-20.
Gozes I., Curr Alzheimer Res 7:685-696, 2010
Gozes I. Curr Pharm Des 17:1040-1044, 2011


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NAP (davunetide) crosses the blood brain
barrier
Stabilizes and repairs microtubules
Reduces Tau hyperphosphrylation
Restores neuronal structure and function
53
GAVISH MOSHE
VEENMAN LEO
PAPADOPOULOS VASSILIOS
• Topic (Mechanisms and therapies, including cell therapy )
• Subject of interest (drug development against neurodegeneration)
• Core technology (Synthesis of specific quinazolines, assays of cell viability
and related processes in cell culture, assays of cell death of glia and neurons in
animal models)
• About the group and major accomplishments
We study the role of the mitochondrial 18 kDa Translocator Protein (TSPO) in
mechanisms related to cell death.
We have developed ligands for the TSPO that prevent cell death otherwise
induced by the TSPO in cell culture and animal models.
• Existing partnership between Israel and Canada
We have published several articles together regarding TSPO function.
• Suggestions for mode of collaboration (for example consortium)
Bilateral partnership for testing of drugs developed by the partners.
The synthetic TSPO ligand MGV-1 protects
astrocytes in the amygdala and the pyriform cortex
A) KA + vehicle
C) KA + MGV1 treatment
B) KA + Vehicle
D) vehicle + vehicle (control)
Gavish Moshe, Veenman Leo, Papadopoulos Vassilios
URI WORMSER
Uri Wormser
Institute of Drug Research
The Hebrew University
[email protected]
Topic: Mechanisms and Therapy, including cell therapy
Subject of Interest: Development of peptides for
autoimmune diseases
Core Technology:
a) Development of peptides for treatment of multiple
sclerosis
Effect of orally
administered IIIM1 (H2A
fragment) in the rat
model
4
Neurological score
Neurological score
Effect of orally administered
IIIM1 (H2A fragment) in the
mouse model
3
2
1
*
0
6
10
*
14
*
*
18
*
22
Time (d) after immunization
3
2
1
*
* *
* *
0
8
12
16
20
24
28
Time (d) after immunization
Effect of orally
administered Japanese
rice extract in the mouse
model
Effect of ip injected RA1 (Japanese rice
peptide) in the mouse model
4
4
1
* *
* * *
Neurological score
RA1
Neurological score
Neurological score
Oryza Japonica extract
2
0
3
control
control
3
Effect of orally administered
RA1 (Japanese rice peptide) in
the mouse model
3
2
1
*
*
* * *
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Time (d) after immunization
2
1
0
0
control
RA1
* * * * *
0 2 4 6 8 10 12 14 16 18 20 22 24 26
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Time (d) after immunization
Time (d) after immunization
b) Development of peptides for treatment
of systemic lupus erythematosus
100
Control
IIIM1
75
50
25
*
*
*
0
0 4 8 12 16 20 24 28
Urinary protein (mg/dl)
Proteinuria (mg/dl)
125
Relevant publications of our group
Effect of 1g/kg UBE (antitrypsin
fragment) in lupus model
Effect of IIIM1 in
lupus model
200
control
UBE
150
100
50
*
0
1
4
*
**
** **
7 10 13 16 19 22 25 28
Days of treatment
Treatment period (days)
•Brodsky, B. et al.Toxicol. Appl. Pharmacol.
229(3), 342-350 (2008).
•Shapira, E et al. J. Autoimmun. 35, 98-106
(2010) .
•Finkelstein, Y et al. Neurotoxicology, 31(5),
608-620 (2010).
•Shapira, E., et al. Lupus 20(5), 463-472
(2011).
•Schussheim, Y., et al. Peptides, 32(1), 125130 (2011).
NAPHTALI SAVION
Topic:
Mechanisms and Therapy, including cell therapy
Subject:
Antioxidant for the treatment of neuro-degenerative diseases –
Autism; MS;
Rational:
Autism and MS are associated with low reserves of glutathione
(GSH) and increase susceptibility to oxidative stress
Molecule:
Allylmercapto-N-Acetyl-Cysteine (ASSNAC)
Mechanism:
ASSNAC slowly attacks free sulfhydryls by the thiol-disulfide
exchange reaction, resulting in NRF2 mediated increased
expression of phase II detoxifying enzymes;
Effects:
Elevation of GSH level by multiple mechanisms:
(I)
(II)
(III)
up-regulation of GCLM expression (GSH synthesis)
supply of cysteine in the form of N-Acetyl-Cysteine (NAC)
up-regulation of cystine transporter (xCT).
Preliminary results:
•
ASSNAC significantly elevates GSH level in endothelial and nerve
derived cell lines and protects these cells from oxidative stress
•
Treatment of experimental autoimmune encephalomyelitis (EAE) mouse
model with ASSNAC (50 mg/kg/day) significantly increases brain GSH
level and attenuates the disease clinical symptoms
Accomplishments:
•
•
•
Patent on eye drops - licensed to Tubilux, Italy
product on market: Lipimix
Patent on platelet function test – co-founder of Matis Medical
product on market: Impact-R
Chief Scientific Consultant and R&D service to ColBar Lifesiences
products on market: Ossix and Evolence
Mode of collaboration:
Joint R&D; License agreement;
DANIEL SEGAL
•
Topic: Therapy
•
Subject of interest: Amyloidogenic diseases.
•
Core technology: Design and synthesis of novel small molecules;
testing them in vitro, in fruit-flies, in mice.
•
About the group: Collaborating with protein chemistry lab of Ehud Gazit, and
mouse neurobiology lab of Dan Frenkel.
•
Major accomplishments: Demonstrated efficacy and lack of toxicity of novel
naphthoquinones, peptidomimetics and cinnamon extracts in inhibiting toxic
amyloids in Alzheimer’s and Parkinson’s disease.
•
Existing partnership between Israel and Canada: None.
•
Suggestions for mode of collaboration: Partnering with academia/Biotech on
drug development and preclinical/clinical testing.
MOUSSA B.H. YOUDIM
ORLY WEINREB
ET
&
NPF
The Canada-Israel Technology Innovation
Partnering Event, Tel Aviv 06 July, 2011
Mechanisms and Therapy;
Neuroprotective-Neurorescue Drugs for Alzheimer’s disease
Moussa B.H. Youdim and Orly Weinreb
Eve Topf Center of Excellence for Neurodegenerative Diseases
Research Technion-Faculty of Medicine, Israel
Eve Topf Center is studying the cascades of molecular and neurochemical
mechanisms involved in the process of neurodegeneration in Alzheimer's,
Parkinson's and Amyotrophic lateral sclerosis diseases, as well as their cellular
and animal models by employing transcriptomic and proteomic profiling.
The ultimate goal is to develop novel neuroprotective and neurorestorative
drugs with disease modifying activity as multi-target compounds.
(Youdim et al., Trends Pharmacol Sci 2005;26:27-35).
ET
&
NPF
The Canada-Israel Technology Innovation
Partnering Event, Tel Aviv 06 July, 2011
Mechanisms and Therapy;
Neuroprotective-Neurorescue Drugs for Alzheimer’s disease
Moussa B.H. Youdim and Orly Weinreb
Eve Topf Center of Excellence for Neurodegenerative Diseases
Research Technion-Faculty of Medicine, Israel
(e-mails: [email protected]; [email protected];
Tel:+972-48295291)
Eve Topf Center is studying the cascades of molecular and neurochemical
mechanisms involved in the process of neurodegeneration in Alzheimer's,
Parkinson's and Amyotrophic lateral sclerosis diseases, as well as their cellular
and animal models by employing transcriptomic and proteomic profiling.
The ultimate goal is to develop novel neuroprotective and neurorestorative
drugs with disease modifying activity as multi-target compounds.
(Youdim et al., Trends Pharmacol Sci 2005;26:27-35).
Neuroprotective-Neurorescue Drugs for Alzheimer’s disease
So far, we have discovered and developed the anti-Parkinsonian drug Azilect® (rasagiline; Teva
Co. Israel) and multi-target drugs ladostigil (TVP3326), now in Phase IIb control clinical studies in
Alzheimer's disease (AD), and in cooperation with company Varinel Inc. (West Chester, PA, USA)
the novel neuroprotective-neurorestorative the iron chelating M30 series.
M30 was designed from the prototype iron chelator, VK28 (5-[4-(2- hydroxyethyl) piperazine-1ylmethyl]-quinoline-8-ol) (Varinel Inc. USA) and enriched with the propargyl moiety of the antiParkinson's MAO-B inhibitor, rasagiline and thus, inherited some of their neuroprotective and
neurorestorative properties ( Zheng et al., J Pept Res 2005;66:190-203).
M30 is a selective iron-chelating and free radical scavenging core structure, which is associated
with inhibition of lipid peroxidation and membrane damage, as well as a unique potent and brain
selective inhibitory activity directed against both monoamine oxidase (MAO)-A and -B, thereby
increasing brain levels of dopamine, serotonin and noradrenalin (Weinreb et al.,
Neurotherapeutics. 2009;6(1):163-74).
M30 possesses neuroprotective/neurorestorative activities against N-methy-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)- and the the proteasome inhibitor, lactacystin- induced neurotoxicity in
mice, similar to those of the rasagiline, the latter properties associated with the propargylamine
moiety (Gal et al., J Neurochem 2005;95:79-88; Zhu W. et al., 2007 Faseb J 21, 3835-44).
Recently, we have demonstrated that M30 involved in the regulation of the Alzheimer's amyloid
precursor protein (APP) levels/processing in neuronal cells cultures models of AD, and
attenuated cerebral A pathology and behavioral deficits in the APP/Presenilin 1 (PS1) double
transgenic mice model of AD (Avramovich-Tirosh et al., J Neurochem 2007;100:490-502;
Kupershmidt et al., Fasbe J. Submitted ).
AMIRAM GOLDBLUM
(HANNA ROSENMANN)
The Hebrew University of Jerusalem Institute for Drug Research
Molecular Modeling and Drug Design Lab
Contact: Amiram Goldblum
[email protected] +972-544-653292
•
•
•
•
•
Topic: Mechanisms and Therapy in Alzheimer’s Disease
Subject of interest: Multitargeted inhibition of beta and gamma
Secretases
Core technology: In Silico, Computational, Prize winning
algorithm (generic algorithm)
About the group and major accomplishments:The Goldblum Group
developed the top optimization algorithm called “Iterative Stochastic
Elimination” (ISE), used for finding “many needles in a haystack” –
achieving unprecedented enrichmetns in several drug discovery
campaigns: acetylcholinesterase inhibitors, Bcr-Abl oligomerization
inhibition, Differential cytoctoxicity to colon cancer cells vs. normal
human and more
Suggestions for mode of collaboration: Need for Organic Synthesis
counterparts and Analytical and Pharmaceutical Chemistry for
measuring molecular properties in pharmacokinetic relevant models
The Hadassah Hebrew University Medical Center, Jerusalem
Department of Neurology, The Agnes Ginges center for Human Neurogenetics
Laboratory of Neurogenetics
Contact: Hanna Rosenmann
[email protected] +972-505-172295
•
•
Topic: Mechanisms and Therapy in Alzheimer’s Disease
Subject of interest: Multitargeted inhibition of beta and gamma
secretases
•
•
•
Core technology: Neuronal cell and animal models for Alzheimer’s
disease (biochemical, immunological, pathological and
behavioral studies)
About the group and major accomplishments: The Rosenmann Group
generated novel animal models for Alzheimer’s disease (using
transgenic, environmental and immunological approaches), and
investigated the effect of environmental risk factors on Alzheimer’s
related tangle pathology. This group developed new therapeutic
approaches, such as tau immunotherapy. The Laboratory of
Molecular Neurogenetics, headed by Hanna Rosenmann, serves as a
National Center for Molecular Genetic Diagnosis and CSF Biomarker
Analysis
Suggestions for mode of collaboration: Further validating of effective
molecules (which reduce amyloid levels and secretase activities) in
cell and animal models
ALEX KOZAK
Dr. Alex Kozak, CEO & President
[email protected]
D-PHARM LTD.
D-Pharm Ltd. 2011 Overview
73
Brief Summary
• Topic:
Mechanisms and Therapy
• Main Interests:
Innovative medicine for
treatment of neurodegenerative diseases
• Core technology: Membrane Active
2+
2+
2+
Chelators (MAC) of Zn , Ca , Cu ions
D-Pharm Ltd. 2011 Overview
74
Brief Summary
• Key achievement: Introduction of First in
class Broad-Spectrum Neuroprotective drugs:
– DP-b99: Phase III in Acute Stroke
– Preclinical products in Dementias & ALS
• Canadian partner: The Canadian Stroke
Consortium
• Collaboration strategy: One-to-One and/or in
Consortium
D-Pharm Ltd. 2011 Overview
75
IMRIC, Hebrew University-Hadassah School of Medicine
Ronit Sharon PhD
Email: [email protected]; tel: 972 2 675 8170
•Topic: Mechanisms of therapy
•Subject of interest: neurodegenerations, Parkinson’s disease
•Core technology: purification and analyses of proteins, molecular and cellular biology,
neuropathology
•About the group: We are interested in biochemical, molecular and cell biology aspects
of neuronal degeneration during aging of the mammalian brain, in particular,
Parkinson’s diseases and the related synucleinopathies.
We perform extensive studies related to the trafficking, processing and secretion of
alpha synuclein (a-Syn), a protein critically implicated in the pathogenesis of Parkinson’s
disease and the synucleinopathies. We have discovered that a-Syn normally occurs in
oligomeric forms and interacts with certain brain lipids. We have further shown that
these oligomeric forms progressively accumulate into Lewy bodies, the prototype
pathogenic insults, when neuronal lipid metabolism is altered. To follow on these
findings, we now seek the identification and control of the specific metabolic pathway
involved in a-Syn toxicity, focusing on specific pathways of gene regulation, for the
development a therapy for Parkinson’s disease.
•Existing partnerships with Canada: none
•Mode of collaboration: a consortium
SHAI RAHIMIPOUR
•
Topic
Mechanisms and therapies, including cell therapy
•


Subject of interest
Multiple Sclerosis (MS)
Alzheimer’s Disease (AD)
•


Core technology
Nano-sized self-assembled neuroprotecting peptides (MS, AD)
Targeted protein microspheres for Amyloid beta clearance (AD)
•



About the group and major accomplishments
2 Research Associates
2 Ph.D. Students
4 MSc. Students
•
About the group and major accomplishments

Development of combinatorial and HTS methods
for discovery of neuroprotecting self-assembled unnatural peptides

Discovery of nano-sized peptides with potent in
vitro anti-inflammatory and neuroprotecting activity

Potent protecting activity in EAE mice model of MS

Development of a novel method to generate surface
modified protein microspheres

Discovery of microspheres that can selectively bind
amyloid beta, inhibit its aggregation and reduce its
toxicity to neurons

Discovery of microspheres that enhance the
phagocytosis of amyloid beta for better clearance
•
Suggestions for mode of collaboration (for example consortium)

Establishment a medium size consortium to study the effect of the
nano-sized peptides and microspheres in related animal models
toward preclinical studies.
DAN T MAJOR
•
•
Topic: Mechanism and Therapy, including cell therapy
Subject of interest: Enzyme mechanisms and rational drug design
using molecular modeling tools
Core technology: Cutting-edge methodologies for molecular
modeling including
•
–
–
–
–
•
Expertise in physical basis for enzyme catalysis and molecular recognition
In-depth modeling tools (quantum/classical simulation software platforms)
Large-scale in-silico drug design tools (protein modeling, docking, screening)
Long experience in racemase enzymes (e.g. Serine racemase – NMDAdependent pathological conditions including Alzheimer’s disease, amyotrophic
lateral sclerosis, and schizophrenia)
About the group and major accomplishments: The Major group is
a theoretical group involved in modeling of biological systems as well
as nanotechnology systems.
–
–
–
–
Group has 10 members (3 post-docs, 2 Ph.D., 5 M.Sc.)
PI is Alon fellow (MOS), Krill prize 2010 (Wolf foundation)
18 publications in first 3.5 years at BIU (PNAS, JACS [×3])
Equipment: Computer cluster of 236 computing cores
HANOCH SENDEROWITZ
Structure/
Sequence
Structure-based
Modeling
Virtual Library
Ligand-based
Modeling
Screening
Known Ligands
Mechanism and Therapy
• Target independent
Virtual Hits
Scoring
• Data dependent
• Virtual screening
Binding Assays
Leads
3D Optimization
In silico
Chemistry
Biology
Drug Candidate
• Molecular simulations
• QSAR/QSPR
• Computational ADME
The group
• One post-doc
• One Ph.D. student
• Six master students
• Multiple software tools
• Medium size computational
cluster
R516
R1070
Y563
F1068
• Open to suggestions about
nature of the collaboration
LAURENT BENISVY
ARIE GRUZMAN
•
•
•
•
Topic : Mechanisms and therapies, including cell therapy
Subject of interest: Potential drugs for neurodegenerative diseases
Core technology: Organic synthesis / in vitro cell experiments
About the group and major accomplishments: New project (2 years)
Work submitted to
Angewandte Chemie
•
•
-
Existing partnership between Israel and Canada: No
Suggestions for mode of collaboration:
In vivo experiments/ BBB crossing experiments
Topic: Novel synthetic chemical
chaperones as a basis for ALS
(Amyotrophic Lateral Sclerosis)
treatment.
Subject of interest: Design and Synthesis of New anti-ALS Therapeutics
Agents.
Core technology: In our search for small molecules that can prevent the formation of
toxic misfolding proteins and aggregates, we have synthesized chemical chaperons
that primarily targeting cell organelles and areas where ALS –related proteins are
aggregating (ER, lysosomes and mitochondria). Refolding by chemical chaperons will
enable lysosome proteolytic enzymes and the proteosome system to cleave the
misfolded proteins properly and decrease ALS progression.
My group: My scientific group has expertise in following fields: organic synthesis,
analytical chemistry, pharmacology, pharmacokinetic and biochemistry. Preliminary
results of our work was published at 2007: Gruzman A, et al. A common molecular signature
in SOD1 for both Sporadic and Familial Amyotrophic Lateral Sclerosis. Proc Natl Acad Sci U S A
2007, 104, 12524-12529.
Existing partnership between Israel and Canada: We do not have yet a
partnerships with Canadian scientists.
ARIE GRUZMAN
Topic: Novel synthetic chemical
chaperones as a basis for ALS
(Amyotrophic Lateral Sclerosis)
treatment.
Subject of interest: Design and Synthesis of New anti-ALS Therapeutics
Agents.
Core technology: In our search for small molecules that can prevent the formation of
toxic misfolding proteins and aggregates, we have synthesized chemical chaperons
that primarily targeting cell organelles and areas where ALS –related proteins are
aggregating (ER, lysosomes and mitochondria). Refolding by chemical chaperons will
enable lysosome proteolytic enzymes and the proteosome system to cleave the
misfolded proteins properly and decrease ALS progression.
My group: My scientific group has expertise in following fields: organic synthesis,
analytical chemistry, pharmacology, pharmacokinetic and biochemistry. Preliminary
results of our work was published at 2007: Gruzman A, et al. A common molecular signature
in SOD1 for both Sporadic and Familial Amyotrophic Lateral Sclerosis. Proc Natl Acad Sci U S A
2007, 104, 12524-12529.
Existing partnership between Israel and Canada: We do not have yet a
partnerships with Canadian scientists.
Suggestions for mode of collaboration: We are looking for cooperation with
Canadian biologists for in vitro and in vivo studies. In particular:
1. Validation of the mechanism of the action of novel chemical chaperones.
2. Testing of the effective in vitro compounds in ALS mice models (mice motor
functions, motor neurons survival, tissue morphology changes, and life span)
3. Optimization of the pharmacokinetic parameters of active in vivo compounds to
improve its bioavailability, oral activity, biodegradation, transmembrane
permeability, potency, and efficacy.
Chemical chaperones
[wtSOD1]damaged
mSOD1 or others
misfolded proteins
[wtSOD1]damaged
mSOD1 or others
misfolded proteins
Accumulation
of toxic SOD-1
species
Aggregation
Motor
neuron
death
Proteolytic
enzymes
Degradation
Cell survival
Accumulation
of toxic SOD-1 species
Aggregation
Motor
neuron
death
Degradation
Cell survival
The final aim of the
project is to develop a
lead compound that is
active in vivo with a
known mechanism of
action and improved
pharmacokinetic
parameters.
Such a compound should
be used in clinical trials in
the next stage of this
drug design project.
JULIA SHIFMAN
Technology: design of protein-protein interactions
•
Subject of interest: design of calmodulinbased sensors and biomarkers
Past accomplishments:
•
–
--
design of calmodulin molecules with high specificity and affinity to
one target protein, e.g CaMKII
Yosef et al, JMB 2009
design of Ca-deficient CaMs
Shifman et al, PNAS 2006
CaMKII
Present collaborators:
Prof. Kevin Truong, •
CaN
Department of Electrical Engineering, University of Toronto – design of
switches and sensors based on Ca-binding proteins.
JACOB GOLENSER
Jacob Golenser
The Hebrew University of Jerusalem
The Kuvin Centre for the Study of Infectious and Tropical
Diseases
Tel. 972 2 6758090, Email: [email protected]
Topic: Mechanisms and Therapy
Subject: Cerebral malaria
Major accomplishments: Proof of concept
Technology: Immunomodulation, Slow drug delivery
Collaboration: Initially- research
Cerebral Malaria is
the most severe
complication of P. falciparum infection
Trophozoites depict ligands (e.g. histidine-rich proteins in knobs)
Sequestration
Knobs
A section of brain taken from a patient with cerebral
malaria. Parasitized red blood cells within capillary
Activation of endothelial cells
by plasmodial and immune
components
Impaired BBB function
Plasma influx to CNS
Angiogenic dysregulation
Th1 responses
Brain edema and
neurological impairment
Rate of cerebral malaria after steroid treatment
Methylprednisolone
hemisuccinate[a]
β-methasone
hemisuccinate[b]
Control
80%
90%
Free drug
90%
67%
Liposomal drug
65%
18%
Mice were treated on days 3, 5, 7, and 9 post-infection with
[a] 10mg/kg/d methylprednisolone hemisuccinate, or [b]
20mg/kg/d β-methasone hemisuccinate, by i.v. injection.
Disease pattern in PbA-infected C57BL/6 mice treated with
artesunate or artemisone twice a day, on days 7-9 post inoculation
Infection outcome
Compound
Dose
Cerebral
malaria
Anemic
malaria
Cured
20µl
4/8
4/8
0/8
2x2.5 mg/kg/d
6/8
2/8
0/8
2x5 mg/kg/d
1/8*
7/8*
0/8
2x2.5 mg/kg/d
0/8*
3/8
5/8*†
2x5 mg/kg/d
0/8*
0/8*†
8/8*†
DMSO
Artesunate
Artemisone
*Significant vs. control.
†Significant vs. artesunate.
NOAM SOBEL
YEHUDAH ROTH
SAGIT SHUSHAN
Prof Noam Sobel, Neurobiology, Weizmann Institute of Science
Dr Yehudah Roth, Otolaryngology, Wolfson Medical Center, TAU
Dr Sagit Shushan, Otolaryngology, Wolfson Medical Center, TAU &
Neurobiology, Weizmann Institute of Science
[email protected] +972-546685688 [email protected] +972-544832075
Session: "Mechanisms and Therapy “
The nose as a diagnostic gateway to the brain
Olfactory research using fMRI and direct electrical and
optical monitoring of the olfactory epithelium in
humans
Olfactory cleft surgery - sampling and intervention,
including development and testing of novel
endoscopy and surgical tools
Rehabilitation in olfactory disorders (i.e. head trauma)
using behavioral and surgical interventions
Brain monitoring of neurodegenerative disorders using
the nose as a diagnostic gateway.
Behavioral Neurology and Otolaryngology relationships, novel concepts of diagnosis
and therapy approaches
Prof Noam Sobel, Neurobiology, Weizmann Institute of Science
Dr Yehudah Roth, Otolaryngology, Wolfson Medical Center, TAU
Dr Sagit Shushan, Otolaryngology, Wolfson Medical Center, TAU &
Neurobiology, Weizmann Institute of Science
[email protected] +972-546685688 [email protected] +972-544832075
Session: "Mechanisms and Therapy “
Sniff-controlled devices to assist the disabled
YOAV MEDAN
EYAL ZADICARIO
InSightec, Nahum Heth 5 Tirat, Carmel, Israel
Yoav Medan PhD, [email protected]
Eyal Zadicario, [email protected]
•
Neurostimulation & Neurotechnologies
•
Translational Research into Clinical Applications
and Clinical Studies in Neuro Therapy
•
Non-invasive focused ultrasound treatments
under MR guidance
•
In last 12 years InSightec achieved;
–
First MR guided Focused Ultrasound Surgery system
accepted and approved as non-invasive therapy in specific
body applications
–
Novel un matched technology for transcranial non-invasive
focused ultrasound technology.
–
5 Clinical Studies approved (FDA/Health Canada) for brain
tumors and functional disorders (Essential Tremor)
–
More than 20 patient treated in on-going clinical trials to date
•
Potential Research include:
– Clinical studies in functional disorders
[PD,ET,epilpesy]
– Brain Tumors
– Stroke
– Targeted Drug Delivery
– Non-Invasive Neurostimulation Projects
•
Existing partnership between Israel and Canada
includes 2 clinical sites in Toronto university for
prostate and brain research.
•
Collaboration such as: Consortium partnerships,
Business collaboration, Additional research
centers for translational and clinical research.
ITSCHAK LAMENSDORF
•
Topic: Mechanisms and Therapy, including cell therapy
•
Subject of interest: Development of relevant models for unmet needs in
neurodegenerative diseases and translational tools for early stage development from
discovery to first in patient
Core technology:
Pharmaseed is a preclinical CRO that has a unique know-how in integrating relevant
experimental readout in CNS pre-clinical animal models (in vitro and in vivo) in order to asses
efficacy and safety.
About the group and major accomplishments:
PharmaSeed is a Research -Oriented CRO with More than 50% PhD Level Personnel. Key
Personnel with an average 10 years of experience working in management positions in
innovative companies.
Existing partnership between Israel and Canadna
None.
Suggestions for mode of collaboration:
Pharmaseed is interested in the development of experimental models that will integrate
translational validated tools in order to integrate them into discovery early pre-clinical
stage. These will be instrumental in evaluating response and kinetics via development of
PK-PD models that are based on allometric (dose-translational) conversion linked to a
“coefficient” of biological-response parameters. In addition, studying disease progress in
correlation with biochemical / genomic biomarkers in animal models (e.g. induction of PD
in diabetic / aged or obese animals) should provide additional understanding as to
personalization of therapy.
We would also like to include “generic” drug phenotype screening that is based on
behavioral outcome as a tool for drug screening.
Development of such tools could be integrated in any targeted CNS disease developmental
program as a unique tool for assessment of potential clinical efficacy. To achieve this goal
Pharmaseed wishes to collaborate and form partnership with pharmaceutical companies or
academic Institutes having the same goal.
MICHAL ROLL
One stop shop for translational R&D activities of 1100 physicians,
60 PhD researchers and their research staff
Interdisciplinary research centers in brain research (focus on advanced
imaging), embryonic and adult stem cells, hospital infections, movement
disorders of the elderly, neurodegenerative diseases, metabolic diseases,
genetic basis of diseases
About 2000 on going clinical trials ( expert internationally registered IRB,
in house auditing, contracts)
Dedicated Early phase clinical trial facility
In house Incubator for Medical Devices
dedicated research facilities,
IP consulting & registering
Technology Transfer - licensing of Technology
Dedicated
labs –
cancer
research,
GI
diseases,
Brain
imaging
research
lab (3
TESLA
MRI)
Genomics
and
bioinform
atics lab
Gait
assessment
lab
Cell
therapy
with GMP
facility
New
animal
facility for
small
animals
113
Neurosurgery at TASMC - Comparative Statistics
Total neurosurgical cases per year - 2600
▪
It is about 40% of cases done in Israel
▪
▪
▪
We do about:
– 60% of malignant brain tumor cases in Israel;
– 90% of epilepsy surgery cases;
– 40% of pediatric neurosurgery cases (~ 400 cases/year at
TASMC)
– 70% of interventional neuroradiology cases (300).
– 90% of peripheral nerve cases.
85% of fMRI (fMRI DTI) examinations (150 /year)
114
TASMC Applied Neuroscience Center
The Mission
Improved healing of the brain by
Prevention of disease & Restoration of
function
The vision
▪
▪
▪
Synergism
– Collaborative clinical & research efforts
Multi-Level
– Neuron to brain, genes to behavior
Applied
– Rapid translation from Lab-bench to
patient-care
115
World leading labs with large scale projects
▪ Neurophysiology (kinematics of gait, cognition)
▪ Neuro genetics ( genotypes, polymorphism, neurofibromatosis)
▪ Advanced brain imaging (fMRI/EEG, DTI, MRS, PET/CT, infant imaging)
World leading clinicians in brain medicine
▪ Neurosurgery (Adult, Pediatric, Functional)
▪ Neurology (e.g. Stroke, Parkinson, Epilepsy, ALS, MS)
▪ Neuroimaging (e.g. Presurgical brain mapping)
Collaboration between 1&2 is implemented continuously
Cutting edge combined technologies on premise
▪ Non-invasive: in-vivo imaging (EEG fMRI), TMS, gait assessment
▪ Invasive: intracranial / deep brain recording and stimulation, neurchemical
mapping (PET/CT).
Access to unique populations for research
▪ Ethnic genetic mutations (Ashkenazi Jews, Arabs), Stressful Life Events
(mandatory military service, wars), Immigrants (Ethiopians, Russians)
116
International Collaborations
Newcastle University
Oxford University,
Oxford
Katholieke University,
Leuven
St. George University,
London
Radboud
University,
Nijmegen
Columbia University,
New York
Beth Israel, New York
Groningen
University,
Groningen
Harvard Medical School, Boston
Einstein Medical School,
New York
Spaulding Rehabilitation Institute,
Boston
University
Pierre & Marie
Curie, Paris
Max Planck Institute,
Leipzig
University of Dresden,
Dresden
Charite University,
Berlin
University
Autonoma,
Barcelona
University of Genoa,
Genoa
University of Bologna,
Bologna
University of Sassari,
Sardinia
Major international competitive non profit
sources for research
NIH
NCI - Radiation Therapy
Oncology Group (RTOG)
ALS Assoc.
NASRAD - brain and
behavior research fund
117
MacDonnell Foundation
National Parkinson
Foundation
MJ Fox Foundation
European Union
research programs
European
Union
research
programs
March of Dimes
Fragile X Foundation
DOD - US army
Michal (Micki) Roll, PhD, MBA
Director, R & D Division, Tel-Aviv Sourasky Medical
Center
• PhD in Pharmacology, Hebrew University
• Post Doc in Neurobiology
• MBA Leicester University, UK
•In charge of all research affairs – grants, clinical
trials, IP (patents) and technology transfer.
[email protected]
www.tasmc.org.il