Thanks John for your post. I have a few comments to add.
From my point of view, research priorities are quite OK. Alpha-syn based therapies, gene therapy with neurotropic factors, cell implants and vaccines have a great potential to work especially if used in combination with one another. It would be similar to cancer treatment protocols of today, a combination of surgery, chemo, radiation and immune therapy. I can even dream of a cure for PD where, GdNF-gene therapy along with newly grafted neuronal cells would replace my dead/dysfunctional neurons and a vaccine/immune modulator would take care of alpha-syn aggregation and inflammation. These types of therapies can happen in the next 5 years. Scientific evidence is there, what we need is translation of that knowledge for patient use. IMHO, clinical trials and regulatory processes need major reforms before we see anything in the market for us.
For the last ten years, I have been following PD literature, exciting research translates into clinical trials, phase 1 open label studies go well, phase 2 double blind studies "fail" and that’s the end of a promising therapeutic. What can we learn from these “failed” trials? First question is:
Did the therapeutic tested really had no beneficial value or the scientific methods used are not adequate enough to evaluate its efficacy? Yes, I do agree that biomarkers would help here, but more is needed.
It is hard to believe that any therapeutic that works well in phase 1, would lose its potency in phase 2 trials. I believe that clinical trial designs are not optimal and need to be modified to suit some of the peculiarities of PD. For edample, We need methodology that would make placebo effect (seen in most PD clinical trials) an asset to a study. Published reports suggest that dopamine is produced (not sure which part of brain) in response to many positive triggers, and hope of getting better with a new treatment can be a great positive trigger. It makes sense to design clinical trials to take advantage of that feature rather than to continue with more sham surgeries to discount its effect. I do not understand why double blind studies and sham surgeries are favored by many PD scientists despite ten years of failed clinical trials. It is time to reevaluate this strategy. I am thankful to a few scientists and many patient advocates who believe that there are better ways of evaluation and these strategies need to be considered. For more on this, See an earlier post by soccertese Interview: Roger Barker, pd research, interesting opinions on current research)
Without novel thinking and PD-specific Clinical study designs, many upcoming therapeutics will fail and years of research is wasted. We cannot let that happen.
My next issue is FDA approval procedures. First let me say that I do t hink we need regulatory agencies like the FDA to approve and monitor the use of drugs and various medical devices. However, we all know how long It takes to get a drug approved (with all the standard procedures in place), we can only imagine the time and paper work involved in approving novel agents such as vaccines and cell therapies for PD. In that context, I very much like the model Dr. Andy Grove proposed to speed up this process. Google Andy Grove and FDA for more details. Briefly, his proposal puts patients in charge of their own treatment options and goes as follows: Once the safety of a drug or therapeutic is established (Phase 1), informed and interested patients seek that therapeutic for treatment while phase 2 trials are going on. This group of patients may not fit into the criteria for a phase 2 study (too young/old, early stages etc.,) but are willing to participate and are well-informed and aware of benefits vs risks of the treatment. this way patients would benefit as well as generate additional information for efficacy studies. One example where this model would work is current NIH gene therapy trial.
These are some of my thoughts for now………….
Thanks
girija