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The NGF System and its interplay with endocannabinoid signalling, from peripheral sensory terminals to the brain: new targets for the development of next generation drugs for neuropathic pain

The objectives of the PAINCAGE proposal address issues which are relevant to the main initiatives at EU and international levels in the field of brain research. In particular, this project is relevant to the EU Joint Programme – Neurodegenerative Disease Research (JPND) initiative. Indeed, chronic pain has been hypothesized as a form of neurodegenerative disorder (Borsook, 2012). The proposed study may uncover mechanisms common to different neurodegenerative disorders, in particular those related to the NGF system, which underlies both CP and neurodegenerative disorders in the strict sense (such as Alzheimer’s disease). Although pain occurs frequently even in individuals with mild AD, pain is underestimated because of the difficult evaluation in these patients. (Jensen-Dahm et al, 2012).

A better understanding of the role of the NGF system in NP and OA, by the PAINCAGE project, might provide an important contribution to the understanding of altered NGF signaling in both pain, and Alzheimer’s disease (http://www.neurodegenerationresearch.eu/).

Moreover, and considering that more than 75% of patients with mild traumatic brain injury (MTBI) reports chronic pain, the PAINCAGE proposal will provide knowledge and new therapeutical opportunities also in this condition, which is highlighted by the International Initiative for Traumatic Brain Injury Research (InTBIR) (http://ec.europa.eu/research/health/medical-research/brain-research/international-initiative_en.html).

Finally, a tight comorbidity is observed between chronic pain states and various neurological and psychiatric disorders, such as depression, stress disorders, anxiety and so on (Bras et al, 2010). For this reason, the PAINCAGE project presents strong elements for cross-interactions with the European Pact for Mental Health (http://ec.europa.eu/health/ph_determinants/life_style/mental/docs/pact_en.pdf)

We envisage that the PAINCAGE project will benefit from interactions with these EU initiatives and that, vice versa, those initiatives will benefit from the feedback and the results of our project.

A key point will be the interaction with the European Medicines Agency (EMA) and US Food and Drug Administration (FDA), as for data dissemination. The results will be presented in scientific meetings and published in the scientific specialised, “peer-reviewed” and non-specialised scientific press.

Numerous endorsement letters from industries and patient’s associations greatly support our studies since the outcomes of this project will significantly improve the patient life quality, the European biotech and pharmaceutical industry, while will reduce social cost and burden. Official signed letters has been received supporting this proposal from the following association of patients, scientific societies, SMEs and large industries:

  • The European Federation of IASP Chapters (EFIC),
  • Belgium Cyprus League Against Rheumatism (CYPLAR), Cyprus
  • Italian Association of Interstitial Cystitis (AICI), Italy
  • International Painful Bladder Foundation (IPBF), Netherlands
  • Italian Society for the study of Headache (SISC), Italy
  • Italian Society for Neuro-Rehabilitation (SIRN), Italy
  • Lay Line Genomics SpA, Roma, Italy (the originator of the PG110 antiNGF antibody under development by Abbott and of the antiTrkA antibody under development by Glemnmark Pharmaceuticals)
  • Lundbeck A/S, Denmark (who holds rights on the sortilin target)
    Glenmark Pharmaceutical S.A., Switzerland (who is developing the antiTrkA mAb licensed from Lay Line Genomics)