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Promising results in the battle against incurable ALS muscle disease

29.11.2004


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 or previous family history. Researchers from VIB (the Flanders Interuniversity Institute for Biotechnology), under the direction of Prof. Peter Carmeliet (Catholic University of Leuven), have previously shown the importance of the VEGF protein in this disease. Now, new research from this group shows that rats with a severe form of ALS live longer following the administration of the VEGF protein as a remedy. These results open up new possibilities for the use of VEGF in the treatment of ALS.

An incurable disease of the muscles

Amyotrophic Lateral Sclerosis (ALS) can strike anyone. The Chinese leader Mao Tse Tung, Russian composer Dimitri Sjostakowitz, the legendary New York Yankee baseball player Lou Gehrig, and astro-physicist Stephen Hawkins have all been afflicted with ALS. In addition, an unusually large number of Italian professional soccer players, airline pilots, and soldiers from the Golf War have been stricken by this fatal disease. About half of them have died within three years − some even in the first year − and usually as a consequence of asphyxiation, while still ‘in full possession of their faculties’.



In ALS, the patient’s nerve bundles that extend to the muscles deteriorate. This causes the patient to lose control over his/her muscles, growing progressively paralyzed − but remaining (disconcertingly) fully alert mentally. The originating mechanism of this deadly disease of deterioration − which has an enormous medico-social impact − remains obscure. At present, the disease is totally untreatable − causing many ALS patients to choose euthanasia, a very controversial solution. However, previous genetic research by Peter Carmeliet and his team at the Catholic University of Leuven has led to the surprising discovery that the vascular endothelial growth factor (VEGF) plays a major role in this disease.

VEGF: a promising track to follow

VEGF is a signaling substance that controls the growth of blood vessels. To a large extent, a tissue in need of oxygen manufactures the protein, thereby developing new blood vessels so that the need for oxygen again diminishes. VEGF also helps neurons survive under stressful conditions. Last year, the work of Peter Carmeliet’s team showed that persons who produce too little VEGF − due to certain variations in the gene that codes for VEGF − have a greater chance of developing ALS. Earlier this year, their research proved that gene therapy with the VEGF gene increased the life expectancy of ALS mice by 30%. But gene therapy is still a controversial method of treatment, whose path to the clinic can be quite long.

VEGF prolongs the life of ALS rats

So, investigation into a possible treatment using the VEGF protein has never been abandoned. Now, research from Erik Storkebaum and Diether Lambrechts, under Peter Carmeliet’s direction, has shown the effectiveness of such a treatment on ALS rats. 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 contracted the disease later than the untreated animals, and they continued to live considerably longer.

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 − by means of a small pump − directly into the cerebrospinal fluid (the fluid that circulates around the brain and the spinal cord) was quite effective.

New hope for patients

Furthermore, this technique permits a patient-oriented approach by enabling the administered dose of the VEGF protein to be easily controlled. Ten years ago, treatment with other proteins was tried on patients with ALS, but without success. At that time, however, this method of continuous administration had not yet been tested on animals with ALS. Therefore, the success of VEGF in these test cases offers new hope for trying out proteins such as VEGF on patients with ALS.

But although these results are very encouraging, there is still a long way to go before there can be talk of a new remedy. Regulated studies on ALS patients will have to demonstrate the therapeutic effect of VEGF on ALS before the protein can be made available as a medicine − and such procedures can easily last several more years.
Relevant scientific publications

The research of the VIB scientists from Peter Carmeliet’s group appears on the website of the authoritative journal Nature Neuroscience (www.nature.com/neurosci)

Sooike Stoops | alfa
Further information:
http://www.vib.be
http://www.nature.com

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