Imagining the cure

What would a cure for Parkinson’s disease look like?

This is a deceptively simple question.  In the public imagination, a cure is something along the lines of ‘take some pills, and the disease goes away’, never to be heard from again.  Cured.  For some infectious diseases, that can actually happen; kill off every last one of the viruses/bacteria/tapeworms, and the disease can be ‘cured’ … if it hasn’t already caused too much damage.  Even in the world of infectious disease, true cures don’t come along very often.

When it comes to Parkinson’s disease, it’s not just that it’s difficult to find a cure, it’s challenging to even envision what a cure would look like.  By the time someone is diagnosed with Parkinson’s disease, around 75% of the dopamine-producing neurons in the substantia nigra are already gone.  To achieve a true cure, you would really like to get at least some of these back, and that’s not at all simple.  In the early days of his foundation, Michael J. Fox was a strong proponent of stem cell research, precisely because it offers one of the few plausible routes to repopulating the lost neurons.  There have been a number of challenges in that field, but this really, truly could happen, someday, especially using neurons grown from a patient’s own cells.  (It would involve drilling a hole in your skull to get them in, but most patients would consider that a minor inconvenience if it actually worked reliably.)  There are theoretically other possible ways to achieve this, such as administering or up-regulating ‘neurotrophic factors’, which promote the growth of new cells.  There have been a number of clinical trials focused on a particular neurotrophic factor called GDNF; early trials showed some promise, but subsequent studies have been disappointing.  Even now, there are still trials going on with GDNF, including at my institution, UCSF; I have some hope for this approach, but it’s a very tricky one.

Although it is important to continue to invest in approaches like these which could lead to a true cure, drugs that stop or even slow disease progression would be an enormous step forward.  While also very challenging, there are quite a few ‘shots on goal’ which I could envision being successful in the relatively near future (in drug discovery terms, that would mean a decade or so).  So-called ‘disease modifying’ drugs would become even more impactful if coupled with advances in early diagnosis of Parkinson’s, theoretically potentially even before people have overt symptoms.  (Also, you can read my discussion of whether rasagiline (Azilect) or levodopa itself might slow disease progression.)

And finally, it is also important not to underestimate the potential impact of further optimizing ‘symptom-modifying’ drugs, i.e., drugs like the current mainstays of Parkinson’s treatment (sinemet, dopamine agonists, MaoB inhibitors, etc.) that reduce Parkinson’s symptoms but don’t change the course of the disease.  This would include: new drugs that target symptoms poorly treated by current drugs; new formulations of levodopa or adjunctive therapies that improve on-time without dyskinesia; and new drugs that reduce the side effects of levodopa such as dyskinesia.  All of these will allow patients to work longer, if they wish, post-diagnosis; remain independent longer; and generally live healthier, more fulfilling lives.  The good news is that major progress is being made in these areas which will improve the lives of patients in the next few years.  Some important new therapeutic options are in fact available right now (duopa, rytary, northera).

The challenge for patients and their doctors is to optimize the ‘cocktail’ of drugs depending on disease stage and other factors.  This is not a trivial task, especially with the new options coming online.  But the recent history of successes in drug development suggest that optimized cocktails can be quite powerful for turning devastating disease into chronic but manageable conditions.  In the treatment of HIV/AIDS, for example, there is no cure, but the availability of multiple effective drugs that each work in different ways has made it possible for many patients, at least in the US and other wealthy countries, to manage the disease successfully for decades.  Arguably, Parkinson’s disease is already half-way there, i.e., if you think Parkinson’s is bad with levodopa, imagine how bad it was before it was available.  Multiple drugs exist that all address the lack of dopamine, with several different mechanisms of action.  With the new options that are becoming available, it is particularly important that people with Parkinson’s learn about the options and work with a Movement Disorders Specialist who will be best prepared to help tailor their drug regimen.