Hope.

First trial in patients with a potential treatment of the incurable ALS muscle disease

2008-12-01 09:00

Leuven (Belgium), Stockholm (Sweden) - Permission has been granted to start the first safety and tolerability trial on patients for a remedy for ALS. ALS is an incurable, paralyzing neurodegenerative disorder that strikes 5 persons in every 100,000. The disease commonly affects healthy people in the most active period of their lives - without warning. Researchers from VIB at the K.U.Leuven have previously shown the possibilities for the use of VEGF in the treatment of ALS through work in animal models. The Swedish Biopharmaceutical company NeuroNova has already built upon this research. Together with UZ Leuven they'll start the first evaluation of safety and tolerability of the drug in patients by the end of this year. This is an important step in the development of a new treatment. It will take several years before the protein can be made available as a medicine.

An incurable disease of the muscles

Amyotrophic Lateral Sclerosis (ALS) can strike anyone. The Chinese leader Mao Tse Tung, Russian composer Dimitri Shostakovich, the legendary New York Yankee baseball player Lou Gehrig, and astro-physicist Stephen Hawking have all been afflicted with ALS. About half of the patients dies within three years - some even in the first year - usually as a consequence of suffocation.

In ALS, the patient's nerve bundles that extend to the muscles deteriorate. As a result the patient loses control of the muscles, and progressively becomes paralyzed. The originating mechanism of this deadly disease of deterioration - which has an enormous medical and social impact - remains obscure. At present, the disease is totally untreatable.

VEGF: a promising candidate drug

VEGF is a substance that controls the growth of blood vessels. Unexpectedly, VEGF also helps neurons survive under stressful conditions. In 2001 Peter Carmeliet's team showed that too little VEGF causes ALS-like symptoms in mice. Later the group of Diether Lambrechts, Wim Robberecht and Peter Carmeliet showed that persons who produce too little VEGF - due to certain variations in the gene that codes for VEGF - have a higher risk of developing ALS. This was the starting point of a search for a possible treatment with the VEGF protein.

Testing the treatment on rats with a severe form of ALS and on rats with a milder form, the researchers found that, in both groups, the VEGF-treated rats manifested the disease later than the untreated animals, and they lived considerably longer.

Using a pump

The researchers also investigated what the optimal technique would be for administering VEGF. An ordinary injection proved to be ineffective. But continuous administration of the VEGF protein directly into the cerebrospinal fluid (the fluid that circulates around the brain and the spinal cord) was quite effective. This was possible by means of a small pump that continuously pumps the VEGF protein in the brain. Furthermore, this technique permits a patient-oriented approach by enabling the administered dose of the VEGF protein to be easily controlled.

A story with several players

These encouraging and promising results were only the first steps on the way to a new remedy. Anders Haegerstrand and his team of the Swedish company NeuroNova have taken the development of the treatment further. After additional studies this research has reached the stage of starting the first trial in patients. Wim Robberecht (UZ Leuven) and Markus Jerling (NeuroNova) will co-ordinate this first trial which is intended to evaluate the safety and tolerability of the drug and the infusion system. It is planned to start at the end of this year, and the investigator Dr Robberecht is currently looking for patients who are eligible for participation. These regulated studies on ALS patients will have to demonstrate the safety of the VEGF administration, and in a later stage the efficacy of VEGF as ALS therapy, before the protein can be made available as a medicine. Such procedures can easily last several years.

Questions

Given that this research can raise a lot of questions for patients, we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: patienteninfo@vib.be . Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.

For practical information concerning the clinical trials you can contact Petra Tilkin (petra.tilkin@uzleuven.be).

More information

For more information on this project, please contact

the VIB Communication Service: +32 9244 66 11

Peter Carmeliet: +32 16 34 61 42 of +32 475 87 13 79

Wim Robberecht: +32 16 33 07 70 (0486 09 85 69)

Anders Haegerstrand, CSO, NeuroNova: +46 8786 0900, anders.haegerstrand@neuronova.com

Markus Jerling, NeuroNova: + 46 8786 0900, markus.jerling@neuronova.com

For more information on NeuroNova, please contact

Ulf Ljungberg, NeuroNova: +46 8786 0900, ulf.ljungberg@neuronova.com

More info on

Relevant scientific publications

• Lambrechts et al., Meta-analysis of VEGF variations in ALS: increased susceptibility in male carriers of the -2578AA genotype (J. Med. Genet., epub, July 2008)
• Zacchigna et al., Neurovascular signalling defects in neurodegeneration (Nature reviews Neuroscience, Vol 9, March 2008, 169-181)
• Lambrechts and Carmeliet, VEGF at the neurovascular interface: Therapeutic implications for motor neuron disease (Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol 1762, Issues 11-12, November-December 2006, 1109-1121)
• Storkebaum et al., Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS (Nature Neuroscience, Vol 8(1), January 2005, 85-92)
• Azzouz et al., Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration (Nature, vol 429,27 May 2004, 413-417)
• Lambrechts et al., VEGF is a modifiere of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death (Nature Genetics, Vol 34(4), August 2003, 383-94)
• Skene & Cleveland, Hypoxia and Lou Gehrig (Nature Genetics, vol 28, June 2001, 107-108)
• Oosthuyse et al., Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration (Nature Genetics, Vol 28, June 2001, 131-138)

Note for the editor

The fundamental preclinical VEGF research was done by Diether Lambrechts, Wim Robberecht and Peter Carmeliet of the VIB Vesalius Research Center, K.U.Leuven, under direction of Peter Carmeliet (www.vib.be/Research/EN/Research+Departments/Vesalius+Research+Center, www.vib.be/Research/EN/Research+Departments/Vesalius+Research+Center/Peter+Carmeliet )

The further development of the research is done by NeuroNova (www.neuronova.com). The clinical trial is done in collaboration with Wim Robberecht, linked to UZ Leuven (www.neurology.kuleuven.be) and the research group ‘Neurobiology' of the VIB Vesalius Research Center, K.U.Leuven (More info: www.vib.be/Research/EN/Research+Departments/Vesalius+Research+Center/Wim+Robberecht).

VIB

VIB, the Flanders Institute for Biotechnology, is a non-profit research institute in the life sciences. Some 1100 scientists and technicians conduct strategic basic research on the molecular mechanisms that control the functioning of the human body, plants, and micro-organisms. Through a close partnership with four Flemish universities - Ghent University, the Katholieke Universiteit Leuven, the University of Antwerp, and the Vrije Universiteit Brussel - and a solid investment program, VIB unites the forces of 65 research groups in a single institute. Their research aims at fundamentally extending the frontiers of our knowledge. Through its technology transfer activities, VIB strives to convert the research results into products for the benefit of consumers and patients. VIB also develops and distributes a broad range of scientifically substantiated information about all aspects of biotechnology. More info at: www.vib.be.

K.U.Leuven

The University of Leuven is Belgium's largest university and one of the oldest universities in Europe, founded in 1425. It is a comprehensive university with 14 faculties, with a long tradition of high-quality interdisciplinary research and teaching. The University of Leuven has over 33,000 students (12 percent international) and over 17,000 staff members (8,600 in the various university departments and 8,700 at UZ Leuven, the university hospital). More info at: www.kuleuven.be

NeuroNova

NeuroNova (www.neuronova.com) is a Swedish bio-pharmaceutical company based in Stockholm, Sweden. NeuroNova has two drug candidates nearing clinical development for Parkinson's disease and ALS. NeuroNova works with neurogenesis and neuroprotection for the treatment of several currently incurable neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and Huntington's disease.

UZ Leuven

UZ Leuven is a university hospital with a reputation throughout Europe as a centre of medical excellence. High-quality, customised patient care, multidisciplinary cooperation, innovation and continuous training all go hand in hand at UZ Leuven. Thanks to the dedication and drive of our motivated staff, we are able to achieve our mission day in, day out.

Mention both VIB and the university

When reporting this research, please always mention VIB as well as the university concerned.