June 7, 2004
[QUICK SUMMARY: New study confirms that VEGF therapy is an effective treatment for ALS in SOD1 mouse model. Plans for human testing are being developed.]
In the May 26, 2004 issue of the journal Nature, investigators from Oxford BioMedica (a biotech company in the UK) demonstrate that delivery of VEGF (Vascular Endothelial Growth Factor) using a lentiviral vector system results in significant delay in onset of symptoms and increased survival in SOD1 mutant mice, the widely studied mouse model of ALS. This confirms reports from earlier mouse studies showing delayed onset and increased survival in mice genetically engineered to express high levels of VEGF bred to mutant SOD1 mice. The current results are important in that they demonstrate a potential therapy for ALS.
Other recent studies have indicated that lower levels of VEGF may be a risk factor in sporadic ALS. "Interest in the role of VEGF in ALS, a growth factor thought to be exclusively involved in the vascular system, resulted from the serendipitous discovery that loss of function of VEGF in mice lead to motor neuron loss and hind limb weakness similar to that seen in the mutant SOD1 mice," said Lucie Bruijn, Ph.D., ALSA's science director and Vice President of Research. "How VEGF may be involved in motor neuron survival is not known."
As reported in the Nature article, a single injection of the lentiviral vector expressing VEGF was administered to various muscles and VEGF could be detected in the motor neurons indicating that the vector system is capable of delivering the growth factor remotely. VEGF was delivered prior to onset of disease symptoms in the mice and showed an increase in survival by 38 days (a 30% increase in survival). These results are similar to the study published last year demonstrating that adenoviral delivery of IGF-1 (insulin-like growth factor-1) delayed the onset and increased survival of the ALS mice. Similar to this earlier study, administration of the growth factor at a time when motor neuron loss has already occurred (as is the case in the clinic) also showed increased survival, albeit to a lesser extent.
Currently, discussions are underway to move this forward into clinical trials. Gene therapy trials are extremely challenging and require rigorous safety studies for FDA approval. In addition, large quantities of clinical grade viral vector are required. Although this viral delivery system has not yet been used clinically, clinical trials using this delivery system for Parkinson's will be underway shortly and would provide support for the potential of this system in the clinic.
Questions and Answers
Q - When will the clinical trials with VEGF be available for people with ALS? A - Preliminary discussions for clinical trials have begun. A timeframe has not been set due to the challenges necessary to overcome as described in the last paragraph above. Work towards a clinical trial will proceed to test safety and secure the necessary viral vector.
Q - Can I get VEGF now and take it before a clinical trial would be available? A - VEGF is a naturally occurring growth factor and is not a commercially available, FDA-approved treatment at this time. The study reported in the journal Nature included administration of VEGF via a viral vector to deliver it to the motor neurons via the muscles. Neither VEGF nor the viral vector is available for individual use at this time.
