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Volume 2
     

Neuropeptides for lung treatment of rare lung diseases, primary and secondary pulmonary hypertension (Neuropeotide Lung Therapy)

   
Project

QLK3-2002-02031

Cell factory area

3.1.3

EU Contribution

2,019,354 Euro

Duration

36 months

Type

DM

Starting date

01 November 2002

Keywords
anti-inflammatory action
anti-proliferative action
binding capacity
inhalation
ABSTRACT

A joint effort of the coordinator and partner 2 identified a group of peptides which are beneficial to patients suffering from primary pulmonary hypertension and other lung disease leading to pulmonary hypertension. Our research demonstrated that these patients lack these peptides, while the receptors are overexpressed in the tissue.

We showed the peptide to function on explanted animal and human tissue, and then developed an effective peptide substitution protocol via inhalation. Currently the first peptide is subject of clinical phase II testing.

Substitution of bioactive peptides by inhalation is an innovative effective therapy for rare lung diseases. We will modify and optimise the peptide characteristics and go through the necessary pharmacological test phase II, to obtain a competitive and effective pharmaceutical product.

OBJECTIVES

Neuropeptides are small bioactive molecules, they convey specific functions via receptors. Our research identified functions of neuropeptides in the lung, and identified patients with diseases where specific small peptides are missing and therefore should be substituted for the benefit of the patient. Our research revealed the effectiveness of peptide inhalation for rare lung diseases like e.g. primary pulmonary hypertension, sarcoidosis and fibrosis. One peptide is currently under clinical test phase II for patients with primary pulmonary hypertension, and (as judged after 60% of the trials done) will pass successfully. We want to use our knowledge on peptide funtions in the lung and perform further pharmacological phase II trials with different subsets of neuropeptides to optimise and establish entirely new therapeutic regimes for rare lung diseases.

DESCRIPTION OF THE WORK

The consortium consists of a SME specialised in peptide engineering, two research laboratories (pharmacology, and cell biology), who will test the identified peptides and smaller subsets of the peptides for specific functions at the cellular and tissue level before the most efficient peptides will be selected for clinical trials. Because we aim at rare diseases the selected peptides will be tested in two national centres which are specialised in the field and recruit patients from a large area beyond national confines.

The SME will provide two peptides that have already been identified by consortium partners to be beneficial for one or more rare lung diseases. It will further provide the consortium with about 40 different shorter peptide subsets with modified peptide length and modified peptide function. These individual subsets will be tested extracorporally on human or on animal tissue for specifity and effectivity with the aim of modifying and optimising the specific peptide function for each disease. In particular the peptides will be tested for vasodilatory effects, anti-inflammatory and anti-proliferative action. At the cellular level receptor binding studies and determination of the kD levels will provide preliminary information on binding capacity of a peptide subset. The three most effective peptides (or subsets) in preclinical tests will be selected for phase II tests.

Patients suffering from primary pulmonary hypertension (PPH), sarcoidosis or secondary forms of hypertension will be recruited in the two clinical centres by experienced senior doctors. In PPH patients serum-concentrations of peptide 1 below the detection threshold in radio immunoassays warrant clinical trials on a substitutional therapy.

DELIVERABLES

Year 1

  • finish clinical approbation testphase II for peptide-1.
  • preclinical test of peptide-2.
  • prepare ethics commission approval for peptide-2.
  • produce peptide derivates from peptide 1.
  • optimise storage and shipment conditions for peptide-1.

Year 2

  • finish clinical approbation testphase II for peptide-2.
  • determine preclinically the bioactivity potential of peptides including antiproliferative and antiinflammatory response.
  • find the modified "best" peptide.

Year 3

  • finish clinical approbation testphase for the "best" peptide.

We will provide the scientific and approbational (at phase II) basis for not less than two new therapeutic strategies for two or more rare lung diseases. The laboratory screening of peptides (bioactivity, biostability, storage conditions) will increase the competitiveness of the new substances on the market.

CONSORTIUM
COORDINATOR
 
Wilhelm Mosgöller
Insitute of Cancer Research
University Vienna
1090 Vienna, Austria
Tel: +43-1-4277 65260
Fax: +43-1-4277 65264
wilhelm.mosgoeller@univie.ac.at
 
PARTNERS
 
Lutz-H. Block
Internal Med-IV,
Univ. Clinic. Vienna
1090 Vienna, Austria
Tel: +43-1-40400 4774
Fax: +43-1-40400 4784
ventzislav.petkov@univie.ac.at

Josef Pfeilschifter
Allg. Pharm. & Toxikol.
Goethe Univ. Frankfrt
60590 Frankfurt/Main, Germany
Tel: +49-69-6301 6951
Fax: +49-69-6301 7942
manderscheid@em.uni-frankfurt.de

Alexander Tschirkov
Cardio surgery
Univ. Clinic Sv. Ekaterina
1000 Sofia, Bulgaria
Tel: +359-2-951 5818
Fax: +359-2-951 5778
B_Atzev@yahoo.com

Fritz Andreae
piChem
Kahngasse 20
8045 Graz, Austria
Tel: +43-316-681 711
Fax: +43-316-681 7114
andreae@pichem.at