ALPHA-MAN

Clinical development of Enzyme Replacement Therapy in alpha-Mannosidosis patients using recombinant human enzyme

 Coordinatore CHRISTIAN-ALBRECHTS-UNIVERSITAET ZU KIEL 

 Organization address address: OLSHAUSENSTRASSE 40
city: KIEL
postcode: 24118

contact info
Titolo: Prof.
Nome: Paul
Cognome: Saftig
Email: send email
Telefono: 494319000000
Fax: 494319000000

 Nazionalità Coordinatore Germany [DE]
 Sito del progetto http://www.alpha-man.eu/index.htm
 Totale costo 8˙028˙469 €
 EC contributo 5˙887˙150 €
 Programma FP7-HEALTH
Specific Programme "Cooperation": Health
 Code Call FP7-HEALTH-2010-single-stage
 Funding Scheme CP-FP
 Anno di inizio 2010
 Periodo (anno-mese-giorno) 2010-10-01   -   2014-03-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    CHRISTIAN-ALBRECHTS-UNIVERSITAET ZU KIEL

 Organization address address: OLSHAUSENSTRASSE 40
city: KIEL
postcode: 24118

contact info
Titolo: Prof.
Nome: Paul
Cognome: Saftig
Email: send email
Telefono: 494319000000
Fax: 494319000000

DE (KIEL) coordinator 593˙128.00
2    REGION HOVEDSTADEN

 Organization address address: KONGENS VAENGE 2
city: HILLEROD
postcode: 3400

contact info
Titolo: Dr.
Nome: Allan Meldgaard
Cognome: Lund
Email: send email
Telefono: 4535453887
Fax: 4535457042

DK (HILLEROD) participant 2˙826˙623.00
3    UNIVERSITATSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAT MAINZ

 Organization address address: Langenbeckstrasse 1
city: Mainz
postcode: 55131

contact info
Titolo: Dr.
Nome: Silvia
Cognome: Tschauder
Email: send email
Telefono: 496131000000
Fax: 496131000000

DE (Mainz) participant 589˙434.00
4    LARIX AS

 Organization address address: TEMPOVEJ 44 - 1st floor
city: BALLERUP
postcode: 2750

contact info
Titolo: Dr.
Nome: Klaus Juel
Cognome: Olsen
Email: send email
Telefono: 4570272221
Fax: 4570272241

DK (BALLERUP) participant 543˙958.00
5 Zymenex AS DK participant 329˙732.00
6    KATHOLIEKE UNIVERSITEIT LEUVEN

 Organization address address: Oude Markt 13
city: LEUVEN
postcode: 3000

contact info
Titolo: Dr.
Nome: Elke
Cognome: Lammertyn
Email: send email
Telefono: 3216320621
Fax: 3216326515

BE (LEUVEN) participant 299˙360.00
7    HOSPICES CIVILS DE LYON

 Organization address address: 3 Quai des Celestins
city: LYON
postcode: 69229

contact info
Titolo: Ms.
Nome: Cecile
Cognome: Legros
Email: send email
Telefono: 33472406860
Fax: 33472406869

FR (LYON) participant 255˙561.00
8    TEKNOLOGISK INSTITUT

 Organization address address: GREGERSENSVEJ 1
city: TAASTRUP
postcode: 2630

contact info
Titolo: Ms.
Nome: Anne Maria
Cognome: Hansen
Email: send email
Telefono: 4572201900
Fax: 4572201919

DK (TAASTRUP) participant 187˙636.00
9    UNILABAS AS

 Organization address address: Nygaardsvej 32
city: Copenhagen
postcode: 2100

contact info
Titolo: Dr.
Nome: Persson
Cognome: Poul
Email: send email
Telefono: +45 33 74 30 20
Fax: +45 33 74 30 75

DK (Copenhagen) participant 115˙864.00
10    UNIVERSITETET I TROMSOE

 Organization address address: Hansine Hansens veg 14
city: TROMSO
postcode: 9037

contact info
Titolo: Mr.
Nome: Stig
Cognome: Orsje
Email: send email
Telefono: 4777646751
Fax: 4777645430

NO (TROMSO) participant 97˙400.00
11    THE UNIVERSITY OF MANCHESTER

 Organization address address: OXFORD ROAD
city: MANCHESTER
postcode: M13 9PL

contact info
Titolo: Ms.
Nome: Liz
Cognome: Fay
Email: send email
Telefono: 441613000000
Fax: 441613000000

UK (MANCHESTER) participant 37˙282.00
12    INSTYTUT POMNIK CENTRUM ZDROWIA DZIECKA

 Organization address address: Aleja Dzieci Polskich 20
city: WARSZAWA
postcode: 4730

contact info
Titolo: Prof.
Nome: Anna
Cognome: Tylki-Szyma?ska
Email: send email
Telefono: 48228157584
Fax: 48228157489

PL (WARSZAWA) participant 11˙172.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

enzyme    orphan    first    biochemical    clinical    therapeutic    treatment    efficient    rhlaman    central    rare    regarding    alpha    http    replacement    nervous    storage    collaborative    human    database    initiated    recombinant    deficiency    man    mouse    disease    trials    data    brain    patients    constitutes    mannosidase    mannosidosis    mutation    pre    immuntolerant    hue    therapy    chronic    laman    patient    model    lysosomal    cells    dose    disorder    caused    ert    genetic    protocol    improvement    mice   

 Obiettivo del progetto (Objective)

'Alpha-Mannosidosis is a rare Lysosomal Storage Disorder with a worldwide incidence of about 1:500 000. This orphan and devastating disease is caused by the deficiency of the lysosomal alpha-mannosidase (LAMAN) which is responsible for the intralysosomal degradation of mannosyl linked oligosaccharides. To date no causative treatment for alpha-Mannosidosis is available and since most of the children are born healthy, an early initiated therapy could contribute to a normal development. To develop an efficient therapy for this disease the collaborative research project EURAMAN and HUE-MAN were initiated within FP5 and FP6, respectively. Within these collaborative networks, European scientists, clinicians and the industry successfully i) developed an efficient pre-clinical Enzyme Replacement Therapy (ERT) protocol using recombinant human (rh) LAMAN in a mouse model for alpha-Mannosidosis, ii) built up a database collecting patient data and iii) defined clinical endpoints for the future clinical trials in alpha-Mannosidosis patients by an European wide natural history study. Furthermore, the HUE-MAN network developed the conditions for a large-scale production of the recombinant enzyme and the way is now paved for the first clinical trials in man, which we aim to realize within FP7. The main objectives of the ALPHA-MAN project are i) the performance of efficient clinical trials (phase I-III) in alpha-Mannosidosis patients, ii) a better understanding of the pathophysiology and the mechanism of how the recombinant enzyme enters the cells of the central nervous system by performing ERT in a newly generated immuntolerant alpha-Mannosidosis mouse model, which allows chronic treatment and iii) the determination of the minimal effective dose with chronic treatment in the immuntolerant mice.'

Introduzione (Teaser)

Existing treatments for the orphan disorder alpha-mannosidosis are mainly supportive and symptomatic. A European study plans to change that by developing a novel enzyme replacement therapy (ERT).

Descrizione progetto (Article)

Alpha-mannosidosis is a rare disease associated with an impaired breakdown of polysaccharides. It is caused by mutations in the gene encoding the lysosomal enzyme alpha-mannosidase (LAMAN), and leads to mental retardation and death in early childhood.

Currently, ERT constitutes the most promising treatment for most lysosomal storage disorders. It entails introduction of the recombinant enzyme into the patient's circulation, which gets picked up by the cells and rescues the lysosome deficiency. However, no ERT has been developed for alpha-mannosidosis.

The scope of the EU-funded http://www.alpha-man.eu/ (ALPHA-MAN) project was to develop a therapeutic strategy using recombinant human enzyme for patients suffering from alpha-mannosidosis. The project based its work on the activities of the predecessor HUE-MAN project regarding large-scale production of the recombinant human enzyme and development of an ERT protocol.

Considerable effort was devoted to finding the optimal drug dose for correcting the central nervous system pathology in mice. A new disease mouse model was developed that recapitulated the human alpha-mannosidosis phenotype. Treatment of mice resulted in an overall improvement of brain-associated symptoms. Researchers also made interesting pre-clinical observations regarding the long-term outcome of ERT based on discovery of the receptors that carry the rhLAMAN across the blood-brain barrier.

The HUE-MAN project performed clinical trials in alpha-mannosidosis patients in centres across Europe, using the medicinal enzyme product rhLAMAN as a therapeutic agent. Enzyme administration was well-tolerated in patients and showed a statistically significant improvement for a number of the biochemical and clinical efficacy end points.

Additionally, the http://amamutdb.no (disease mutation database) has been further developed to include new data from 27 additional patients. In total, the mutation database now contains genetic, biochemical and clinical data on more than 240 patients. Collectively, this information provides a comprehensive picture of the genetic aetiology of alpha-mannosidosis.

The success of the ALPHA-MAN project to establish rhLAMAN as an ERT approach to the treatment of alpha-mannosidosis was communicated through press releases and conference presentations. It constitutes the first specific and evidence-based therapeutic intervention for this untreatable disease.

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