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Drugs to Treat Alzheimer Disease

#A-1646


Development and Study of Pharmacologically Active Compounds to Treat/Prevent Alzheimer Disease

Tech Area / Field

  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • BIO-CHM/Biochemistry/Biotechnology
  • CHE-OTH/Other/Chemistry
  • MED-DIS/Disease Surveillance/Medicine
  • MED-DRG/Drug Discovery/Medicine

Status
3 Approved without Funding

Registration date
21.05.2008

Leading Institute
Institute of Molecular Biology, Armenia, Yerevan

Supporting institutes

  • “Diagen Plus” Diagnostic laboratory, Armenia, Yerevan

Collaborators

  • CNRS / Institut de Pharmacologie Moleculaire et Cellulaire, France, Valbonne\nUniversitat de Barcelona / Institut d'Investigacio Biomedica de Bellivitge, Spain, Barcelona\nUniversity of Texas at San Antonio / College of Sciences, USA, TX, San Antonio

Project summary

Mental and neurological disorders are highly prevalent worldwide with 450 million people estimated to be suffering from them. The study conducted by WHO has demonstrated that magnitude and burden of neurological disorders are huge and that they are priority health problems globally. The proportionate share of the total global burden of disease due to neuropsychiatric disorders is projected to rise to 14.7% by 2020. Alzheimer's (AD) is a neurodegenerative disorder characterized by a progressive decline in memory, thinking, comprehension, calculation, language, learning capacity and judgment sufficient to impair personal activities of daily living and having tremendous impact on the lives of affected inpiduals, their families, and society as a whole. The rate of occurrence of AD doubles every five years for those between the 65 and 85 years of age. It is predicted that the incidence of AD will increase threefold within next 50 years. At present, the human society doesn’t have effective medical treatment against AD, in spite of more than a one hundred years experience investigating AD. The discovery and development of new medicines to fight AD is a problem of vital importance. The investigation of molecular mechanisms involved in brain degenerative disorders and development of new drugs to improve the patients’ condition is a significant issue in public health throughout the world. Thus, serious attention needs to be paid to the risk factors and preventive measures that may be taken to postpone the AD onset, if not prevent the appearance. Among the approaches towards AD modifying treatment and blocking the initial steps of amyloid formation has attracted the most attention but progress in this area is slow. The regulation of reactive oxygen levels by activation of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione-dependent enzymes ensuring the endogenous cell self-defense is in the spotlight as well.

There is a clinical trial in the USA using lithium to treat AD. Using of lithium salts is conditioned by successful experiments of treatment in some cases of neurological disorders. These promote us to synthesis new physiological compounds of lithium and investigate the pharmacokinetic and toxicity of new substances at AD. Our preliminary experiments on cell cultures revealed that lithium salts was not toxic for cells at concentrations many times higher than physiological ones.

Thus the objectives of the proposed project are the study of biological effects, toxicity and dose depending activity of new synthesized lithium compounds as potential medications to prevent/treat AD. Results obtained on animals in vivo and on cells in vitro will suggest the applicability and expediency of effective compounds as potential pharmacological preparation. The recommendations on new active substances application as pharmacological preparation will be developed. The recommendations on the new active substances application for preclinical trials will be prepared. The results of the project proposed will be of scientific and practical interest. A new approach will be applied to elucidate mechanisms of neurodegenerative disorders. New active substances will be tested and may be recommended as potential medicines to treat the AD. The objective of this proposed project is having basic and applied value for science, pharmacology, and clinical medicine.

Researchers from the Institute of Molecular Biology and “Diagen Plus” Diagnostic Laboratory will participate in the project. They have essential experience in joint work and in performance of international research programs. The research team from the Institute of Molecular Biology (Leading Institution) has more than a twenty years experience investigating the brain diseases. Project participants are highly qualified experts in neurology, biochemistry, molecular biology, genetics, cell biology, toxicology, and chemistry. The research teams are involved 3 Professors, 9 PhDs, and 3 technicians.

The proposed project implementation will exert long-term influence on further investigations of different lithium compounds in various neurodegenerative disorders. New biologically active substances will throw this valuable product available for common usage in science, pharmacology, and medicine to ensure the future commercial success of this project. The results and objective of this project will open for the project participants a long-term prospective to develop new active preparations to treat various neurodegenerative disorders. The project proposed fully meets the ISTC goals and promotes them to be realized.

In the frames of this project using the test-systems in vivo (amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice knowing as in vivo experimental model of AD, provided by collaborator Prof. Isidro Ferrer) and in vitro (neural cell cultures which will be transfected with cloned beta amyloid precursor protein knowing to be a major neuropathological characteristics of AD) the main biological effects of new synthesized substances will be studied: the regeneration processes in damaged central nervous systems and cultured neurons, the determination of lipid peroxidation, the antioxidant enzymes activities and total antioxidant activity, the acute and chronic toxicity, cyto- and genotoxicity, and contents of galactosylceramides, ganglioside and products of their hydrolytic dissociation ceramide and sphingosine, and composition of phospholipids. The dose depending timetable of new active lithium compounds will be elaborate. The recommendations on new active substances application as pharmacological preparation will be developed. The recommendations on the new active substances application for preclinical trials to prevent and/or treat AD will be prepared.

In the process of the project implementation the participants and collaborators will continuously change the information on work progress results obtained, etc. The collaborators will comment interim and final reports presented to ISTC, will carry out cross-examination of results and technical examination of participant activity. Joint experiments will be performed using collaborators’ equipment. Joint workshops will be organized periodically.

In the process of the project implementation a number of techniques will be applied: molecular biology techniques (PCR, cloning), transfection and expression of beta amyloid precursor protein; immunohisto- and immunocytochemistry; determination of lipid peroxidation, antioxidant enzymes activities and total antioxidant activity; methods of galactosylceramide, ganglyoside, ceramide, sphingosine, and phospholipids extraction and determination; estimation of toxicity, cyto- and genotoxisity in vivo and in vitro.


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The International Science and Technology Center (ISTC) is an intergovernmental organization connecting scientists from Kazakhstan, Armenia, Tajikistan, Kyrgyzstan, and Georgia with their peers and research organizations in the EU, Japan, Republic of Korea, Norway and the United States.

 

ISTC facilitates international science projects and assists the global scientific and business community to source and engage with CIS and Georgian institutes that develop or possess an excellence of scientific know-how.

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