PharmaCog Steering Committee discusses project’s progress
Thursday 03 March 2011
At its meeting in Paris on 3 and 4 March 2011, the PharmaCog Steering Committee was able to look back on a full year of PharmaCog activities and achievements.
During the first year of the project PharmaCog has largely focused on 7 key areas:
1) Maximising the opportunity of the diverse experience and background of the PharmaCog team to optimise clinical and pre-clinical study designs. Information gathered from literature reviews, protocols and data from studies conducted by participating EFPIA partners has been combined to optimise 3 clinical study designs and parallel pre-clinical research plans. Protocols have been finalised and enrolment is due to begin 2nd quarter of 2011 and literature reviews have been valorised by submission to scientific journals.
2) Harmonisation and standardisation of endpoints across all participating pre-clinical and clinical research sites. Endpoints were selected on the basis of sensitivity to disease progression, pharmacological intervention and translatability between species. Protocols for each endpoint have been agreed and procedures have been harmonised and standardised across all participating sites.
3) Investigating the feasibility of sleep deprivation as a model of cognitive impairment in pre-clinical models. Pilot studies have been completed demonstrating that robust cognitive impairment can be induced in a variety of models and can be reversed by Donepezil and Memantine.
4) Understanding the dynamic range for novel biomarkers in the models of Alzheimer’s Disease. A range of pilot studies have been conducted to investigate the magnitude of change in the novel biomarkers, 2- deoxy glucose, MRI, DTI and MRI. The outcomes of this work will be presented in 5 posters at The Alzheimer's Association 2011 International Conference on Alzheimer's Disease (ICAD, to be held in Paris in July 2011.
5) Establishment of communication tools to support the effective dissemination of PharmaCog. A PharmaCog extranet facility has been developed to facilitate communication between partners including draft documents, meeting materials, timelines, financial and project management documents. A section dedicated to PharmaCog has also been established on the Alzheimer Europe website. Regular updates on PharmaCog have been through the Alzheimer Europe newsletter and annual conference.
6) Establishment of Standard Operating procedures (SOPs) and guidance document for the governance of clinical trial preparation and management, data management, and publication policies in PharmaCog. Twenty-one SOPs were drafted and agreed by all partners to cover all key aspects of protocol development, human biological tissue sample management, data management and publication procedures.
7) Establishment of an ethics advisory board to oversee the ethical and scientific conduct of PharmaCog. An internal Ethics Advisory Board has been established to oversee and guide the project regarding ethical and safety aspects and scientific conduct of the study. Given the translational nature of PharmaCog this committee focuses on both human ethics and animal welfare.
8) PharmaCog partners have started to work closely with investigators in other major Alzheimer Initiatives across Europe and the USA. PharmaCog PK/PD groups have started effective collaboration with Coalition Against Major Disease (CAMD) initiative led by Marc Cantillon. First effective meeting will be held in Brussels in the coming months hosted by the IMI office (http://www.c-path.org/CAMD.cfm/). PharmaCog investigators worked closely with Alzheimer's Disease Neuroimaging Initiative (ADNi) with the help of Prof Giovanni Frisoni in particular to develop the WP5 clinical trial.
In addition, the Steering Committee was informed of some important administrative changes:
- Dr. Ceri Davies, Vice President, External Alliance & Development at GSK, has taken over as new EFPIA coordinator of the project from Dr. Elaine Irving who was thanked by the steering committee for her commitment and dedication to the project,
- Eisai Ltd joined the consortium and has started to work on the pre-clinical and clinical workpackages of PharmaCog. Eisai as a new partner brings the number of global pharmaceutical companies involved in the project to 12.
Next steps for PharmaCog
The second year of PharmaCog will see the recruitment of patients into three clinical studies
1) to validate the utility of sleep deprivation induced cognitive impairment in assessing cognitive enhancing agents,
2) to identify central pharmacodynamic markers sensitive to donepezil and memantine,
3) to identify markers sensitive to disease progression and predictive of conversion from Mild-cognitive impairment to Alzheimer’s disease.
Pre-clinical work will focus on the longitudinal assessment of single, double and triple APP transgenic mice and lemurs to identify translatable markers that correlate with amyloid pathology in each of these models. Touch-screen technology will be established and validated for the assessment of cognitive decline in APP transgenic animals.
Sleep deprivation and hypoxia will be validated as models for assessing cognitive enhancing agents and central pharmacodynamic markers will be identified.
In all clinical and preclinical studies PK samples have already been collected in preclinical assessments and will continue to be collected to allow the establishment of mathematical models to describe each model and the translational relationship with the clinic.