Current Research: Gene Therapy
Drug treatments for diseases of the central nervous system (CNS) are difficult to deliver to the target. This is because the CNS is not accessible or receptive to injections or drugs given by mouth. Also, the CNS is shielded from unusual compounds in the blood by a layer of specialized cells known as the blood-brain barrier. Thus, most compounds given in the diet or by intravenous injection cannot cross into the brain or spinal cord and are removed by the liver or kidneys.
The PNR&D is investigating new methods of delivering drugs to the CNS. This type of treatment will then be applicable to many neurodegenerative diseases and injured nerves. One way to deliver drugs to the CNS is to influence the cells there to make the drug at the target site. To do this, a gene that codes for a drug or therapeutic compound is inserted into CNS cells. Naturally occurring methods for the transfer of genes are being utilized by PNR&D investigators. The common cold virus effectively infects many types of cell. The genes that give patients a cold have been removed and replaced with neuron protective genes.
1 = dorsal (anterior) horn, 2 = dorsal root ganglion (home of the sensory neurons), 3 = sciatic nerve, 4 = muscle, 5 = skin..
A prototype virus containing the gene for insulin-like growth factor I is being tested in a rat model of nerve trauma. PNR&D investigators are currently exploring the best ways to target the virus to the CNS by injecting directly into nerves or into the muscles that the nerves connect with. The PNR&D team always includes a training neurosurgeon who is invaluable in developing the virus delivery techniques. These neurosurgeons work with the PNR&D for up to one year to gain basic research experience and support the PNR&D mission. Accumulated research by the neurosurgeons have demonstrated that the nerves transport injected virus to the spinal cord. This technique has several advantages: 1) A factor or therapy is delivered to the specific neurons affected by a disease; 2) There is no need to inject through healthy tissue to reach the affected cells, avoiding additional tissue damage; 3) Healthy cells are not exposed to therapeutics that they do not need. Preliminary results show that the gene therapy improves the rat’s ability to heal after neurological damage.
PNR&D investigators and others have established the gene therapy technique in animal models of human disease including ALS and trauma. These successes have led to the first stages of planning a clinical trial of IGF-I gene therapy in human ALS. More information concerning this clinical trial will be available in the near future.
A paper entitled “Gene therapy with VEGF in the crushed recurrent laryngeal nerve” has been submitted for publication.
