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Medición de la expresión del gen PRKACA para predecir la respuesta a análogos de purina en pacientes

Resumen

Tipo:
Oferta Tecnológica
Referencia:
TOES20170213002
Publicado:
06/03/2017
Caducidad:
06/03/2018
Resumen:
Un instituto español de investigación médica ha desarrollado una herramienta para predecir la respuesta a la quimioterapia con fludarabina y el riesgo de padecer la enfermedad de injerto contra huésped. La tecnología propuesta consiste en un procedimiento para determinar la expresión del gen PRKACA y la actividad de cAMP como herramienta de utilidad para este fin. El instituto busca compañías farmacéuticas interesadas en comercializar la herramienta bajo acuerdos de licencia, servicio o comercialización, o en establecer acuerdos de investigación para continuar con el desarrollo. Las compañías farmacéuticas pueden estar interesadas en desarrollar inhibidores de cAMPK (quinasa dependiente de cAMP) para potenciar el efecto de los análogos de purina.

Details

Tittle:
Measure of PRKACA expression to predict in patients the response to purine analogues
Summary:
A Spanish Healthcare Research Institute has developed a tool to predict the response to chemotherapy with fludarabine and the risk of suffering Graft-Versus-Host disease.
The Institute would like to talk to pharmaceutical companies interested in commercialising this tool under a license or services or commercial agreement, or in a research cooperation agreement to develop it in greater detail.
Description:
A Spanish Healthcare Research Institute, working in the field of biomedical sciences, has developed a tool to predict the response to chemotherapy with fludarabine and the risk of suffering Graft-Versus-Host disease.

Fludarabine is a purine nucleoside analogous, which act as cytostatic drug widely used for the treatment of hematological and solid tumors, especially for lymphoproliferative disorders including chronic lymphocytic leukemia, low-grade lymphoma and prolymphocytic leukemia. This drug, in combination with alkylating agents and monoclonal antibodies, has more than 95% of satisfactory responses. As a consecuence of the inmunosuppressant effect that it has over lymphocytes B and T, Fludarabine is the most used drug today in patients with allogenic transplant and its objective is to facilitate the implant of new progenitor cells and to decrease the toxicity of the tissue, hence decreasing the initial risk of Graft-Versus-Host disease (GVHD).
Allogeneic hematopoietic stem cell transplant (Allo-HSCT) is the only curative option for many patients with leukemia, primary or acquired marrow failure, primary immunodeficiency or inborn genetic diseases. GVHD is a frequent complication of allo-HSCT, and consists of the destruction of host tissues by donor effector lymphocytes. The incidence of the acute form of GVHD (aGVHD) has been estimated at 10%-80%, with symptoms usually during 2-3 weeks post allo-HSCT, and 30-70% for chronic GVHD (cGVHD) in allo-HSCT recipients, surviving beyond 100 days, with an average start of 4-6 months after transplant.

Fludarabine is negatively charged, so it needs to be dephosphorylated prior to enter the cells by facilitated transport. Once inside the cell, it is activated by re-phosphorylation to its triphosphate form (F-Ara-ATP) by deoxycitidine kinase. Several enzymes involved in DNA synthesis are targets of the action of Fludarabine, including DNA polymerase and DNA primase, since it competes with the normal dATP nucleotide. In addition, Fludarabine is incorporated into RNA and DNA, resulting in chain synthesis termination, and its location at the 3´-terminus makes it impossible for ligase I to join it to an adjacent strand of DNA, leading to premature chain termination and cell death. Besides, in non-dividing cells, Fludarabine incorporates into DNA by using the DNA repair mechanisms, but inhibits the nucleotide excision repair (NER) process, causing irreversible damage.

The results in vitro show that F-Ara-ATP can be dephosphorylated and therefore inactivated by cAMP dependent protein kinase (cAMPK), so the Institute can measure its expression (PRKACA gene) and its activity, so both combined can act as a biomarker of response to fludarabine and to other purine analogues. It can be useful to predict the responses to chemotherapy with fludarabine in patients with acute leukemia and lynphoproliferative syndromes and the risk of suffering GVHD after an allogenic transplant.

So the technical solution proposed consists in a procedure to determine the expression of PRKACA gene and the activity of cAMP as a useful tool for this purpose.

The Research Institute would like to talk to companies interested in commercializing this tool or in a research cooperation agreement to develop it. Pharmaceutical companies could be interested in the development of cAMPK inhibitors to potenciate the effect of purine analogues.
Advantages and Innovations:
There is no response predictor to purine analogues in the market.

The main competitive advantages of this new tool are:

- Measuring the PRKACA gene expression and the cAMPK activity we can predict the response to the chemoterapic treatment with fludarabine in patients with acute leukemia and lymphoproliferative syndromes, as well as the risk of suffering Graft-Versus-Host disease after an allogeneic transplant.

- It will allow a more personalized therapy, because some mutations in this gene can entail refractoriness to the treatment.
Stage of Development:
Under development/lab tested
IPs:
Patent(s) applied for but not yet granted
CommeR Statunts Regarding IPR Status:
A Spanish patent application covering this product was filed on 22th december, 2016

Partner sought

Type and Role of Partner Sought:
Pharmaceutical companies could be interested in the development of cAMPK inhibitors to potenciate the effect of purine analogues and also hospitals which use these kind of drugs.

The Institute would like to talk to companies interested in commercializing this tool under a commercial, license or services agreement. Also a research cooperation agreement to develop it will be considered.


Client

Type and Size of Client:
R&D Institution
Already Engaged in Trans-National Cooperation:
Si
Languages Spoken:
English
French
Spanish

Keywords

Technology Keywords:
06002007 Ensayos in vitro, experimentos
06002003 Tecnología de enzimas