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Nuevos compuestos patentados para el tratamiento sintomático y modificador de la enfermedad de Alzheimer

Resumen

Tipo:
Oferta Tecnológica
Referencia:
TOES20141205003
Publicado:
07/12/2015
Caducidad:
13/06/2016
Resumen:
Un centro de investigación español ha desarrollado moléculas pequeñas para el tratamiento sintomático y modificador de la enfermedad de Alzheimer orientado a dos objetivos, epigenético y no epigenético. Las moléculas muestran una mejora en modelos conductuales, patología amiloide y Tau y restauración sináptica. El nuevo modo de acción se valida in vivo e in vitro. Este tratamiento frena el avance de la enfermedad y mejora los síntomas. Se buscan socios académicos y empresas biofarmacéuticas con el fin de establecer acuerdos de cooperación en I+D, licencia, etc.

Details

Tittle:
Novel proprietary compounds for symptomatic and disease-modifying treatment of Alzheimer´s disease
Summary:
A private Spanish Research Center has developed small molecules for symptomatic and disease-modifying treatment of Alzheimer´s Disease hitting two targets, epigenetic and non-epigenetic. Proprietary molecules show improvement in behavioural models, Tau and amyloid pathology and synapse restoration. Novel mode of action is validated in vivo and in vivo. The Center is open to partnerships (R-Y-D cooperation, licensing...) for further development with academia and biopharmaceutical companies.
Description:
A private Spanish Research Center combines solid basic biology science with early preclinical drug development capabilities within a context of clinical patient care. Everything is oriented to solve unmet medical problems for the benefit of the patient and the society.

The Center has facilities and processes for target-based and phenotypic drug discovery and early development of new therapeutic agents, up to the lead optimization stage. Noteworthy are: the collection of biological samples; the animal facilities, which include from knock-out mice to larger species; the genomics, proteomics and bioinformatics unit; and the imaging unit, providing services of microscopy, non-invasive image acquisition of laboratory animals and quantitative image analysis.
Strategic linkage with the University Hospital enables and promotes the bidirectional flow of ´bench-to-bed´ knowledge and backwards.

Conscious of the complexity of this endeavor, the Center operates in a context of Open Innovation, and willingly collaborates with other research institutions, biotechnology and pharmaceutical companies, public institutions and investors.

Proprietary compounds:
Novel proprietary compounds bind two targets, epigenetic and non-epigenetic and show in vivo efficacy and safety.

Therapeutic Scope:
Alzheimer´s disease (AD) is particularly devastating since there is no cure, no way to prevent it and no proven way to slow its progression. Currently, approximately 18 million people worldwide are afflicted with this disease and it is projected to reach over 30 million by 2025.
Management of AD represents a huge unmet need; thus, discovery and development of more effective therapies are critical for worldwide public health and health-care systems.

Indication:
Novel strategy for symptomatic -Y- disease-modifying treatment of Alzheimer´s disease.

Patient need addressed:
Substantially slow down the progression of Alzheimer´s disease and improve symptoms.

Mode of Action:
Novel mode of action (MoA) has been proposed.
­- Targeting two independent and synergistic pathways, epigenetic and non-epigenetic, involved in synaptic plasticity and memory.
­- In addition, this novel MoA leads to reduction of Tau and beta-amyloid pathologies and synapse restoration.

Validation process.
Pharmacological tool compounds were identified and utilized for in vitro and in vivo Proof-of-Concept (PoC):
­- In vitro, using primary neuronal cultures: synergistic effect in related targets.
­- In vivo, using AD transgenic mice (Tg2576): behavioral studies and AD pathological marks.
- Hitting two targets, epigenetic and non-epigenetic.

Development Stage:
Multifactorial optimization process guided to the discovery of the proprietary lead compound CM-414:
- Binding affinities, for both targets, at nM range.
- Efficacy, according to AD related markers (e.g. C99, pTau, ...) in Tg2576 primary cultures, at low nM range.
- Crossing BBB and showing in vivo functional response -epigenetic mark- at brain level (hippocampus).
- Safety window, efficacy vs toxicity, >2.5 log units.

Effect of CM-414 in AD Tg2576 mice:
- After chronic treatment (3 weeks), showed a restoration of memory deficits in two different behavioural tasks: the Fear Conditioning and the Morris Water Maze test (A-C).
- The memory recovery induced by CM-414 was maintained after a washout period of 4 weeks in aged Tg2576 mice (Morris Water Maze test) (D-E).
- AD pathological marks analysis, from treated Tg2576 mice, showed significant decrease in amyloid (APP, C99 -Y- A-Y-beta;42) and Tau pathology (F-G) as well as reversal in deficits in spine density (H).
- Gene expression profile, in hippocampus of treated Tg2576 mice leads to identify the over-expression of memory related genes

The Center is open to a range of partnerships (R-Y-D cooperation, financing, joint venture, licensing) with academia and biopharmaceutical companies interested in further development.
Advantages and Innovations:
Novel MoA has been identified and validated. Targeting two different pathways leads to improvement in behavioral models as well as in Tau and amyloid pathology.
First-in-class. Novel proprietary compounds, dual inhibitors, aim to substantially slow down the progression of Alzheimer´s disease and improve symptoms.
4 weeks after treatment discontinuation, memory recovery was maintained.
Stage of Development:
Under development/lab tested
IPs:
Patent(s) applied for but not yet granted

Partner sought

Type and Role of Partner Sought:
- Type of partner sought: academia, biotechs and pharmaceutical companies.
- Specific area of activity of the partner: Medicine.
- Task to be performed: To facilitate the advancement of the research, with the ultimate goal of improving patient quality of life. By joining capabilities and resources, this win-win cooperation facilitates the advancement in the different research stages, from target validation to lead optimization or early candidate development.

Client

Type and Size of Client:
R&D Institution
Already Engaged in Trans-National Cooperation:
No
Languages Spoken:
English
Spanish

Keywords

Technology Keywords:
06001014 Neurología, investigación cerebral