Some questions about NIL-A.
The premise of the recent exchange here is that NIL-A showed positive results in animals and hence is a promising candidate for human PD.
Now we all know that animals don't get Parkinson's disease - that they need to be treated with 6-OHDA or MPTP or some other nasty compound to induce PD-like symptoms - so what is the basis for confidence that NIL-A will translate well into humans? I am somewhat familiar with neurotrophic and neurotropic compounds but I'm certainly not up to speed with the neural survival- and regeneration capabilities of FKBP-like immunophillins. I've begun my homework and hope to address this later this weekend on the Neuroscience thread. However, there's been an historical concern in using any factor that causes nerve 'growth': specificity. NIL-A is orally available (i.e. it readily crosses the BBB). As a proposed PD treatment, NIL-A must, by definition, target dopaminergic neurons in the substantia nigra. Is there evidence for this? In other words, is there evidence that NIL-A does NOT also causes growth of non-dopaminergic neurons? If NIL-A leads to any degree of non-specific growth, this is serious 'toxicity' and could produce as many new problems as the improvement in PD symtomology Guilford is claiming. In addition, PD commonly becomes manifest when 80%+ of the DA nigral neurons have degenerated. Is the company claiming it can somehow 'replace' these lost neurons or that NIL-A will stabilize the number at the point when treatment began (or, more conservatively, NIL-A will mitigate the rate of loss)? Also, what was the evidence from the animal studies that NIL-A re-established the CORRECT neuron-to-neuron connections. Again, simple increased survival or 'regeneration' is one thing, but synapses are lost before a neuron dies and these synapses must be restored in their proper configuration for the word 'regeneration' to any meaning at all.
It's always prudent to keep in mind that while NIL-A may do everything that AMGN and GLFD claim, it also may produce no clinical benefit. It's better to begin with this stance and have your doubts proven wrong than to accept the company's claims without scrutiny.
Please note that I've been looking at GLFD as one of the first stocks to place in a Neuroscience portfolio I'm starting on that thread. The issues raised above are questions I'm asking myself when I compare the claims of the company versus what I know to be the incredibly difficult issue of treating a neurodegenerative disease. When reading through the NIL-A section in the company's most recent 10-K, I kept saying to myself, 'yes....but'. There is scant discussion on the actual scientific basis and rationale for using NIL-A or other immunophillin ligands for neurodegenerative disease (other than a reference to Sol Snyder) and there is no mention in the 'Risk Factor' section that extrapolation of animal data to humans is fraught with peril especially in the case of Parkinson's Disease. None of the basic science concerns noted above - concerns that have been extant for many years - are discussed either. There's no doubt that accepting the company's premise about the promise of NIL-A is a huge risk factor.
I understand the idea that any treatment that has the potential of improving the outcome of PD is worth pursuing. I also think it important to take an objective and earthbound perspective on the likely degree of improvement and to appreciate the possibility of substantial side effects. |
