Scott, these are excellent thought provoking questions. I don't pretend to be an expert on NIL-A. But, I've never let ignorance get in my way before. So, I'll take a crack at your questions. Hopefully someone more knowledgeable will correct my errors and fill in the blank spaces.
NIL-A does not specifically target dopaminergic neurons. One of the reasons that it appears to be so useful is that it has generalized neurotrophic effects. The question you raise is whether this is dangerous. Well, it may be. But, there is reason to believe that it will be quite safe. NIL-A goes not regenerate neurons. It leads to collateral sprouting in spared neurons. These collaterals grow and innervate the synaptic space vacated by the dead cells. Collateral sprouting is going on all of the time in the CNS. However, since virtually all the space available for a synapse to attach to other neurons is occupied, these collaterals are never able to connect to a receiving cell. When they don't they atrophy and wither away, having no effect. So promoting collateral sprouting in systems that are healthy should have little or no effect. However, in systems where there is degeneration, it could have a very positive influence.
The treatment of choice for PD is l-DOPA. This has the effect of increasing release of DA from the spared terminals and appears to ameliorate the symptom of PD. This means that it is not an intricate data stream that is important here. Rather it is the amount of DA secreted that makes a difference. DA in general appears to have tonic widespread effects and is thus important for general tone of the CNS. So, it's manipulation has been particularly useful for psychotropic medications. It also means that an effective treatment would not have to replace specific cells, but rather simply replace the missing DA. It would not be necessary to reconnect to the CORRECT neuron. The collateral sprouting induced by NIL-A could fit this bill nicely.
I agree completely with your caution. All the animal data in the world doesn't prove that it will work in humans. I was amazed to see Amgen enter into this deal before NIL-A was ever in a human. That was a very risky strategy on their part. (But, then again they paid $20 million for Leptin). It explains why so much of the deal is based on developmental contingencies.
BTW: does anyone know if GLFD gets a payment from Amgen for NIL-A moving into P II trials?
Scott, the worry I have about NIL-A is that some of the animal findings have not been replicated in other labs. This is a concern. So, I, like you, will remain cautious and skeptical regarding NIL-A. However, I am very enthusiastic about its potential. This is a typical situation in biotech. We put our money down based on potential. Then, hope that that potential will be realized. If it is we will profit handsomely. If not, then ......
I'd rather not think about it.
Best regards
John de C |
