New treatment for Schizophrenia/Nuevo tratamiento para la Esquizofreniabraincosm
BRAINco Biopharma Schizophrenia Drug Discovery project brochure. Licensing opportunity.
Folleto descriptivo del proyecto de búsqueda y desarrollo de fármacos en Esquizofrenia. Oportunidad de licencia.
The document discusses the human sensory system and neurological functions. It describes how the sensory system processes sensory information through sensory receptors, transduction, and neural pathways in the central and peripheral nervous systems. It discusses the main sensory modalities of vision, hearing, taste, smell, and touch, and how stimuli are coded by sensory receptors in terms of type, intensity, location, and duration. The anatomy and physiology of neurons, neuroglia, and the central and peripheral nervous systems are also summarized.
The document discusses the human sensory system and neurological functions. It describes how the sensory system processes sensory information through receptors, transduction, and neural pathways in the central and peripheral nervous systems. It explains that sensory receptors detect different stimulus modalities like touch, temperature, and sound. The sensory signals are transmitted through ascending pathways like the dorsal column-medial lemniscus pathway and spinothalamic tract to regions in the brain involved in perception.
Judith Ford Presentation - SRF Webinar Sep 13, 2012wef
Neurophysiological studies using EEG and ERPs have provided insights into auditory verbal hallucinations. Studies compare neural activity during hallucination periods versus non-hallucination periods within subjects (symptom capture) and between hallucinating and non-hallucinating patients. Symptom capture studies show involvement of auditory cortex but findings are inconsistent. Studies comparing patients find hallucinators have smaller ERP responses to probes, suggesting voices disrupt processing of external auditory events.
This document discusses coma and consciousness. It provides an overview of the historical understanding of consciousness, defines normal consciousness, and describes various disorders of consciousness including coma. Coma is defined as a state of unresponsiveness with eyes closed and no response to stimuli. The document outlines the clinical assessment and treatment of patients in comatose states and notes that longer periods of coma are associated with poorer prognosis.
The document discusses an integrated therapy approach for autism developed by DOAST in Chennai, India. It combines principles from yoga, Ayurveda, and Siddha with modern medical practices. A key hypothesis is that autism may be linked to chronic inflammation and treating downstream inflammation could help restore upstream molecular order and neuronal connectivity. The therapy uses herbal medicines, dietary changes, and yoga techniques. Assessments found improvements in behaviors, cognition, and other domains for patients who complied with the therapy. Further proposed research includes molecular studies to validate the hypotheses.
New treatment for Schizophrenia/Nuevo tratamiento para la Esquizofreniabraincosm
BRAINco Biopharma Schizophrenia Drug Discovery project brochure. Licensing opportunity.
Folleto descriptivo del proyecto de búsqueda y desarrollo de fármacos en Esquizofrenia. Oportunidad de licencia.
The document discusses the human sensory system and neurological functions. It describes how the sensory system processes sensory information through sensory receptors, transduction, and neural pathways in the central and peripheral nervous systems. It discusses the main sensory modalities of vision, hearing, taste, smell, and touch, and how stimuli are coded by sensory receptors in terms of type, intensity, location, and duration. The anatomy and physiology of neurons, neuroglia, and the central and peripheral nervous systems are also summarized.
The document discusses the human sensory system and neurological functions. It describes how the sensory system processes sensory information through receptors, transduction, and neural pathways in the central and peripheral nervous systems. It explains that sensory receptors detect different stimulus modalities like touch, temperature, and sound. The sensory signals are transmitted through ascending pathways like the dorsal column-medial lemniscus pathway and spinothalamic tract to regions in the brain involved in perception.
Judith Ford Presentation - SRF Webinar Sep 13, 2012wef
Neurophysiological studies using EEG and ERPs have provided insights into auditory verbal hallucinations. Studies compare neural activity during hallucination periods versus non-hallucination periods within subjects (symptom capture) and between hallucinating and non-hallucinating patients. Symptom capture studies show involvement of auditory cortex but findings are inconsistent. Studies comparing patients find hallucinators have smaller ERP responses to probes, suggesting voices disrupt processing of external auditory events.
This document discusses coma and consciousness. It provides an overview of the historical understanding of consciousness, defines normal consciousness, and describes various disorders of consciousness including coma. Coma is defined as a state of unresponsiveness with eyes closed and no response to stimuli. The document outlines the clinical assessment and treatment of patients in comatose states and notes that longer periods of coma are associated with poorer prognosis.
The document discusses an integrated therapy approach for autism developed by DOAST in Chennai, India. It combines principles from yoga, Ayurveda, and Siddha with modern medical practices. A key hypothesis is that autism may be linked to chronic inflammation and treating downstream inflammation could help restore upstream molecular order and neuronal connectivity. The therapy uses herbal medicines, dietary changes, and yoga techniques. Assessments found improvements in behaviors, cognition, and other domains for patients who complied with the therapy. Further proposed research includes molecular studies to validate the hypotheses.
User friendly presentation describing how to perform BRAINchip, a test that predicts the individual response to antipsychotic and/or antidepressant drug treatment. BRAINco Biopharma
El documento describe el proceso para realizarse el BRAINchip, un análisis genético que determina el riesgo de toxicidad o ineficacia de diferentes fármacos psiquiátricos y de TDAH. El proceso implica contactar con la compañía, acudir a la clínica más cercana para la recogida de muestra, y recibir posteriormente un informe con los riesgos de cada fármaco.
Brainchip es un DNAchip de genotipado que determina los polimorfismos implicados en el metabolismo de la
mayoría de los fármacos Antipsicóticos y Antidepresivos. BRAINchip predice la respuesta a los tratamientos antipsicóticos y antidepresivos.
Brainchip is a genotyping DNAchip which determines the polymorphisms involved in the metabolism of Antipsychotic
and Antidepressant drugs.
Brainchip predicts drug response to antidepressants and antipsychotics.
New treatment for Major Depression/Nuevo tratamiento para la Depresión Mayorbraincosm
BRAINco Biopharma Major Depression Drug Discovery project brochure. Licensing opportunity.
Folleto descriptivo del proyecto de búsqueda y desarrollo de fármacos en Depresión Mayor. Oportunidad de licencia.
BRAINco Biopharma is part of the Progenika Group and develops personalized treatments for nervous system diseases. BRAINco has drug discovery programs for schizophrenia, major depression, and multiple sclerosis based on novel targets identified through proteomic and genomic studies. BRAINco also develops pharmacogenomic tools to improve drug safety and efficacy. The company utilizes an open innovation model and collaborates with research centers and CROs to advance its pipeline.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
User friendly presentation describing how to perform BRAINchip, a test that predicts the individual response to antipsychotic and/or antidepressant drug treatment. BRAINco Biopharma
El documento describe el proceso para realizarse el BRAINchip, un análisis genético que determina el riesgo de toxicidad o ineficacia de diferentes fármacos psiquiátricos y de TDAH. El proceso implica contactar con la compañía, acudir a la clínica más cercana para la recogida de muestra, y recibir posteriormente un informe con los riesgos de cada fármaco.
Brainchip es un DNAchip de genotipado que determina los polimorfismos implicados en el metabolismo de la
mayoría de los fármacos Antipsicóticos y Antidepresivos. BRAINchip predice la respuesta a los tratamientos antipsicóticos y antidepresivos.
Brainchip is a genotyping DNAchip which determines the polymorphisms involved in the metabolism of Antipsychotic
and Antidepressant drugs.
Brainchip predicts drug response to antidepressants and antipsychotics.
New treatment for Major Depression/Nuevo tratamiento para la Depresión Mayorbraincosm
BRAINco Biopharma Major Depression Drug Discovery project brochure. Licensing opportunity.
Folleto descriptivo del proyecto de búsqueda y desarrollo de fármacos en Depresión Mayor. Oportunidad de licencia.
BRAINco Biopharma is part of the Progenika Group and develops personalized treatments for nervous system diseases. BRAINco has drug discovery programs for schizophrenia, major depression, and multiple sclerosis based on novel targets identified through proteomic and genomic studies. BRAINco also develops pharmacogenomic tools to improve drug safety and efficacy. The company utilizes an open innovation model and collaborates with research centers and CROs to advance its pipeline.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
1.
New treatm
ment for Schizophrenia
a
Exocy
ytosis mod
dulators for the tre
f eatment of Schizop
phrenia
Advant
tages:
• A novel me
echanism of action: the exocyt
tosis impli
icated dire
ectly
on
o neurotr
ransmissio
on.
• A novel the
erapeutic target whi has bee found al
ich en ltered in h
human
postmortem brain fr
p m rom schizophrenic pa
atients, and has been
d
validated i unique cellular an transge
v in c nd enic anima models.
al
• M
Molecules modulatin the syst
ng tem have a
already be identif
een fied.
Hypothesis:
H
BRAINco ha carried o extensiv genomic and proteo
B as out ve omic analysis of human postmorte brain tis
n em ssues
fr
rom schizopphrenic pat
tients that h commi
had itted suicid Increased expressio levels of a key pro
de. on otein
in
nvolved in n
neurotransm
mitter releas have been found in th prefron cortex.
se n heir ntal
Ref
filling with
Early en
ndosome
neurotransmitters
H+
H+
Sy
ynaptic vesicles
s
Docking Priming Fusion
ATP Ca2+
a Endocytosis
E
Ca2+
Presy
ynaptic membrane
BRAINco
o target Ca2+
+
Syn
naptic Cleft
Neurotransmitter Posts
synaptic membra
ane
receptor
r NEUROT
TRANSMISSIO
ON
The modu
ulation of ne
eurotransm
mitter relea may pla a crucial role in the future of antipsycho
ase ay l e otics.
2.
Devel
lopmen Stage Candidate Id
nt e: dentification
BAC
CKGROUN
ND
BRA AINco aims to validate th implication of the targe in the etiop
he n et pathogenia o the disease using in vit as well as
of e tro s
in viv models an find molecules with a good preclin
vo nd nical profile that affect ne
eurotransmit release an present
tter nd
efficacy in the tra
ansgenic anim over exp
mal pressing the t
target of inte
erest.
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s very tissue hoowever the proteins invo
p olved in this m
machinery are tissue
a
specific: d
different isofo
forms are exppressed depen nding on the cell type.
e
BRAINco expects to an nticipate mo
olecules specificity issues combining two strategie 1) Cell ba
s es: ased approac
ch
is based on neuronal c
n cellular moddels, 2) Targe focused ap
et pproach done with specifi isoforms from the bra
e fic f ain.
Assay Target Primary Screening
Targe
et development validation assay campaing Candiidate for
Hit to Lead
ident
tification & precli
inical
Lead Opt.
devellopment
In s
silico Virtual In‐vitro
moodeling screening testing
Animal model Mole
ecule testing
Biomarker dis
B scovery
Figure 1 Workflow of th project
1: he
TOO GENER
OL RATION A
AND TARG
GET VALIDATION
A rel
levant increa of the targ has been found in hum postmortem brain
ase get n man
from Schizophren subject, m
m nia modulated by antipsycho treatmen (Fig.1).
otic nt
Then BRAINco has validated the target a animal and cellular lev
n, at d vels, the tools
s
gene
erated for val
lidation will b used to de
be evelop the pr
roject.
Cel based assa
ll ay:
Seve cellular b
eral based assays have been set up to mea
asure neurotra
ansmitter Figure 1. Target expression in brain post mo
n ortem
relea with diffe
ase erent read-ou radioactivity, fluores
uts: scent probes and other tissue.
bioellectrical assa
ays:
The effect of target on exxocytosis ha been valida
as ated
using severa cellular ba
al ased assays, a an exampl
as le
results from the radioact assay in Fig.2.
m tive
The radioact assay ha been adapt to HTS a
tive as ted and
validated for screening
r
A fluorescen assay base on a molecular probe i
nt ed is
being adapte to HCS.
ed Figure 2. Neuro
otransmitters relea left: when target is overexpressed
ase,
and right: when target is knocked down.
n
Seve assays in cell lines de
eral n erived from d
different peri
ipheral tissue have been set up in ord to evalua molecules
es n der ate
tissue specificity.
3.
Devel
lopmen Stage Candidate Id
nt e: dentification
Traansgenic (TG animal m
G) model:
An an nimal model over-expres
l ssing the targ of interest has been generated.
rget g
Behav vioral, morphological, bi
iochemical a molecula characteriz
and ar zations have shown that t transgenic mice present a
m
schizo ophrenia like phenotype.
e .
Behavio oral Morph hological alt teration Func ctional
Increase i locomotion
in Brain vo olume decrea ase. Reduc ction in long term potenti iation.
activity (o open field). Reductio in white matter
on m Alteraation of neuro otransmitter
Social int teraction defefects. tracks. systemms.
in sensoring gating
Deficit n Increase in ventricle volume
e Abnor rmality in basal cortical
(prepulse inhibition) F Fig.3. (Fig.4). oscilla
atory activity (Fig.5).
y
in working me
Deficit n emory
(new obje recognitio
ect on).
Fig
gure 3. Deficit in PPI in TG mice Figure 4. Chan
nges in brain and ventricles Figure 5. LTP TG vs. Control (C5 & CBA/C57)
F G 57
eated with antipsy
(tre ychotic) volume betwee WT and transg
en genic
We are aiming a in vivo Pro of Conce of the can
at oof ept ndidates in ou animal mo and other classical animal mode
ur odel a els
befo the end o the year.
ore of
CAN NDIDATE F FINDING
Cellular based approach:
Sever chemical starting poi have bee identified so far.
ral l ints en d
A screening with the Pr
g restwick libra (1120 FD approval compounds) has been pe
ary DA l erformed and the hits
d
identified r represent orally available drugs.
A second screening wit a diverse l
th library (9652 compounds has been d
2 s) done and a sp pecific chemi family
ical
has been ou
utlined.
A third scre
eening is bei planned w a differe methodology and a la
ing with ent arger and mo diverse lib
ore brary.
Tarrget focused approach:
d
A virrtual screenin has been p
ng performed ag gainst two dr ruggable site es
identi
tified in the t target by in s silico modeli ing.
A prelimina virtual sc
ary creening has been perform in order to
med r
validate both sites.
A virtual sc
creening with millions of compounds is now bein
h f s ng
performed. The molecu obtained will be teste in a protei
ules d ed in-
protein inte eraction assay adapted to HTS (the HTRF assay Fig.6).
y F
Figure 6. HTRF assay Target/ Target partner (different
p
conce fferent fluorescent TAGs)
entrations and dif
4.
Su
ummarize
Schizophren is curren estimat to affect around 1.1% of the U populati and its total medical
S nia ntly ted t US ion t
cost reache €35 bill
c ed lion. Current antipsycchotics lack of effica
k acy particu
ularly again cognitiv
nst ve
symptoms, together w
s with their side effects, has stress the need for mor effective treatment
, sed re e ts.
However, al
H lmost none of the pre
e esent drugs under deve elopment ar based on a new me
re n echanisms o
of
action
a
BRAINco h carried out extens
B has sive genomi and prot
ic teomic anal lyses of huuman postm mortem brai in
tissues from schizophre
m enic patient that had c
ts committed suicide. Alt
s terations in the express
sion levels o
of
certain prote involve in exocyt
c eins ed tosis have b
been found in the prefro
i ontal cortex of these pa
x atients. Othe
er
research gro
r oups have further suppported thes findings, involving the exocy
se ytosis machhinery in thhis
complex dis
c sorder.
BRAINco h built u a drug discovery program based on e
B has up b exocytosis and neurot transmission
n.
Nowadays t target has been val
N the lidated at human, anim and cell
mal lular levels. The comp
. pany has alsso
developed d
d different ceellular and biochemica assays used for fin
al nding molec cules that modulate th
m he
release of ne
r eurotransmi itters. BRA
AINco set up two appro
p oaches in or
rder to find molecules that regulate
for
f one part, the mecha
, anism of exoocytosis and for a seco part, the interaction between the target an
d ond e n nd
it main part
ts tner involve in this m
ed mechanism.
In
I addition, the express sion of the target has aalready been found alte
n ered in Schhizophrenia as well as i in
others disea
o ases. At gennetic level, m
mutations in the target have also b
n been identif ntile epileptic
fied in infan
encephalopa
e athy. BRAIN will as
Nco ssess the bi
iochemical and functioonal alterati of the exocytosis i
ion e in
different tissues, includ
d ding the an nimal mode as well as patients in order to define the strategy fo
el, a o e or
patient strati
p ification.
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