The “NEUROCURE PROJECT” A Spanish Joint Venture to Develop a Pharmacological Target in Dementia of Lewy Bodies

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A joint venture founded by three Spanish Biotechnology companies headquartered in Barcelona, Oryzon genomics, Advancell in vitro technologies and Crystax Pharmaceuticals, has embarked on a three years program to evaluate the potential of a new pharmacological target for the Dementia of Lewy Bodies (DLB). The joint venture will collaborate with Laboratorios ESTEVE, the second biggest Spanish pharma, with the final goal to come up with a clinical candidate and looking for a partner to complete development. The project has been additionally co-funded by an especial grant from the Catalan Government and received the award for the most innovative joint venture project in 2004 in Barcelona.

In the developed world, the progressive aging of populations is producing a steady increase in senile dementias. Most of them will be diagnosed as Alzheimer disease (AD), but there are also other less well known dementias with high frequency and prevalence. This is the case of the Dementia of Lewy Bodies (DLB) which is, after AD, the second more frequent in the elder. In 1996, scientists published guidelines for the diagnosis of dementia with Lewy bodies (McKeith IG, et al, Neurology, vol 47, pp 1113-1114, Nov 1996). In various autopsy studies performed throughout the world, this form of dementia, referred to as DLB, has been observed to represent 15-25% of all cases.

The cause of this neurodegenerative disease is uncertain. DLB has some similarities with Parkinsons disease (PD) but with widespread cortical pathological states, leading to dementia, fluctuating cognition, and characteristic visual hallucinations. The deposition of aggregates of synuclein in neurons and glia suggests that a common pathogenic mechanism may exist for these disorders. However, DLB has some distinguishing clinical features of its own. Genetic studies are making some progress in revealing a matrix of different genes which may contribute to development of DLB. This appears to be complex but may explain firstly the mentioned relationship of DLB to the other primary Lewy body disorders including Parkinson's disease and secondly the association with Alzheimer's disease. It remains to be seen whether genetic testing will be sufficiently simple to help in clinical diagnosis.

Unfortunately, so far there is no efficient therapy and nowadays treatment is ONLY SYMPTOMATIC, often involving the use of medication to control the parkinsonian and psychiatric symptoms. One of the key hystopathological hallmarks of PARKINSON (PD) and Dementia of Lewy Bodies is the accumulation of LEWY bodies, insoluble proteinaceous deposits. Their composition varies but they always contain: Ubiquitin, Ubiquinated proteins and Alpha-synnuclein. A malfunction of the ubiquitin/proteasome system (UPS) may be associated with their formation. Either, it may reflect an unsuccessful attempt by the cell to remove them.

Oryzon genomics started in early 2004 a prospective genomic program using customized DNA-chips to identify early biomarkers in synucleinopathies in collaboration with the School of Medicine of the University of Barcelona. One of the possible candidates was noticed to have reduced expression in brains of patients suffering form dementia compared to controls and that the target was also involved in the dynamics of the agressome. Due to other previously reported observations linking this target to PD, and possibly to AD, the idea of further explore the potential of this pharmacological target for the Dementia of Lewy Bodies was considered.

Upon these bases, a joint venture named The “NEUROCURE PROJECT” was set-up with Advancell In vitro-cell technology, a Catalan start-up specialized in vitro human cellular systems responsible for setting-up HT in vitro assays for the target and to explore the functional and toxicological effects of the compounds to be developed.

The third partner of the triad was CrystaX, a successful start-up company working in the field of structure-based drug discovery, where they perform processes ranging from gene cloning to the 3D structure elucidation of pharmacological targets. CrystaX uses the latest techniques in X Rays diffraction. Then, using virtual and fragment screening, CrystaX identifies new lead compounds for the development of novel pharmaceutical compounds.

A fourth company joined the project later: LABORATORIOS ESTEVE, the second largest Spanish pharmaceutical company, and with special interest in CNS indications, which will provide its library of compounds to be screened. The final goal for the joint venture and ESTEVE is to identify a clinical candidate and looking for a partner to complete development.

Including the academic researchers and the four companies, an interdisciplinary team of almost 20 scientists will spend the next three years in a collaborative project to identify pharmacological leads compounds able to stop or reduce the progression of the disease. The “NEUROCURE PROJECT” will also have access to the robotic scientific platforms of the Barcelona Science Park

This is one of the first big alliances announced between Catalan biotechs and a Big Spanish pharma and will hopefully started a new way of producing bigger and more integrated projects in the Spanish drug discovery arena. The project has been patronized by the Industry Departament from Generalitat de Catalunya, (SIE-Projected Consorciats).


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Carlos Buesa Arjol
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