Of Avigen's upcoming news events, I'm most looking forward to the IND its Parkinson's AAV vector coding for the release of aromatic amino acid decarboxylase. Here's a quote from the 10K re upcoming milestones:
<<We intend to submit an investigational new drug (IND) application with the Food and Drug Administration (FDA) for our second lead product candidate for the treatment of Parkinson’s disease later in 2003. Our product candidate for the treatment for hemophilia A, Coagulin-A™, is currently in preclinical development and based on the results of preclinical studies in animals and the results of our clinical trials for hemophilia B, we expect to submit an IND with the FDA for Coagulin-A in 2004.>>
Also from the 10K, a more complete description of the Parkinson's program:
<<Parkinson’s disease is a neurological disorder that affects an estimated 1.5 million people in the United States and Europe. Characterized by an increase in spontaneous movements, gait difficulty, postural instability, rigidity and tremor, Parkinson’s disease results from a decrease in the levels of dopamine, a neurotransmitter essential to the control of movement in the brain. Dopamine is produced in a region of the brain called the substantia nigra by the interaction of tyrosine and aromatic amino acid decarboxylase, or AADC. In patients who suffer from Parkinson’s disease, cells in this area of the brain degenerate over time for unknown reasons, which reduces the patient’s ability to produce dopamine.
Currently, the primary treatment for Parkinson’s disease is oral administration of L-dopa, a dopamine precursor, which can be converted to dopamine inside the brain by AADC. Dopamine itself cannot be administered directly as it cannot pass through the blood/brain barrier. While this approach can help relieve symptoms for several years, it becomes progressively less effective as the level of AADC produced by the substantia nigra continues to decline as those cells continue to die. To compensate for this decline in effectiveness, dosage levels of L-dopa must be increased, which can result in serious side effects. Based on information obtained from industry reports, we believe that the current amount spent on drugs to treat Parkinson’s disease worldwide is approximately $1 billion per year.
Our strategy for treating Parkinson’s disease is to use an AAV vector to deliver the gene for AADC directly to the striatum, the part of the brain that needs dopamine to control movement, bypassing the degenerating substantia nigra. Then, when the patient takes L-dopa, it is converted to dopamine only in the region of the brain where it is needed. This “pro-drug” approach enables the patient and physician to control the level of dopamine in the brain by regulating how much L-dopa is taken. We believe this approach has the potential to offer significant advantages to patients by prolonging the effectiveness of L-dopa.
Initial research studies on both rodent and primate model systems have been promising and suggest that our AAV gene therapy for Parkinson’s disease may be effective in supplementing existing therapies. Primates with induced Parkinson’s disease respond like humans to the administration of L-dopa. As the number of functioning cells in the substantia nigra declines, the effectiveness of taking L-dopa also declines. Primates with severe Parkinson’s symptoms that no longer respond to L-dopa, when treated with our AAV-AADC, have shown significant clinical improvement. This improvement is shown to correlate with measured increases in dopamine activity in the brains of these animals. Several primates treated more than two years ago continue to show gene expression and a decrease in Parkinson’s symptoms when treated with L-dopa.
We have been working closely with an independent collaborator on these studies over the past few years and in June 2001, our collaborator presented data at the American Society for Gene Therapy meeting in Seattle that demonstrated improved preliminary results in animals. Based on the results of these earlier studies, in October 2001 we announced our intent to use our AAV technology and manufacturing expertise in connection with expanded preclinical studies in order to assess the safety and efficacy of this approach prior to seeking to initiate human clinical studies. We expect to file an IND application for our Parkinson’s product later in 2003.>>
Marc |
