On Thursday, December 13th, The Michael J. Fox Foundation (MJFF) hosted the final event of the year in its Hot Topics in Parkinson's disease (PD) Research Seminar Series: “PD Research 2012: How Far We've Come and What Lies Ahead.” The webinar, which is now available on demand, was led by MJFF CEO Todd Sherer, PhD, and Associate Director of Research Programs Maurizio Facheris, MD, MSc.
Sherer and Facheris answered some participant questions live, but time ran out before they could get to everyone’s. As promised, we answer a few more here:
Does Parkinson’s begin in the gut, and work its way to the parts of the brain that cause the motor symptoms of the disease?
MJFF: Researchers are currently investigating this hypothesis, based on the research of Heiko Braak, MD. The idea is that the disease may start not in the substantia nigra but in the gastrointestinal system and the olfactory bulb, the part of the brain that controls sense of smell. Researchers have posited that the alpha-synuclein clumps found in all people with Parkinson's may form in these parts of the body first, before migrating to other parts of the brain. This hypothesis is tied to two symptoms that may signal early Parkinson's: loss of smell and constipation.
If it's true that alpha-synuclein clumps occur in the gut first, and if researchers can find the clumps and break them up before they reach the brain, it may become possible to treat Parkinson's before major neurological damage occurs. This is still a relatively big “if”; there remains significant work to be done though to verify that Braak’s Hypothesis is in fact scientifically viable.
But research continues to move forward: One company, called QR Pharma, is developing a drug called Posiphen that they hope could break up clumps of alpha-synuclein in the intestine and the brain. And scientists from Rush University Medical Center are investigating whether colonoscopies could one day be used to predict PD.
Several questions about Deep Brain Stimulation:
Has DBS been shown to be indefinitely beneficial?
MJFF: Last year, one study found that the effects of Deep Brain Stimulation (DBS) were sustained for up to a period of ten years. It’s possible that these effects could be sustained for a longer period of time, but DBS as a treatment for Parkinson’s just hasn’t been around long enough for us to know. Scientists will continue to study the effects of DBS over the long-term. A reminder: DBS isn't for everyone, but it can be an effective treatment for those who qualify and are willing to undergo brain surgery, which is of course a nontrivial decision.
Have there been any improvements in DBS that will soon be available?
MJFF: Several companies are working diligently to improve upon DBS technology. Just a few months ago, a new device was approved for use in Europe. The new system is unique in that it allows physicians to selectively control the electric current delivered through each individual electrode emitted from the device that is implanted in the brain. This might help doctors to better control where the electric current goes in the brain, which could have implications for improved treatment for patients. More stringent tests than those done in Europe are necessary in order to gain approval by the U.S. Food and Drug Administration, so the device will likely not be available on the American market for some time. An important point: It’s not yet clear whether the device is actually better than existing devices, or if it’s merely ‘different.’
Has there been any progress in finding new areas of the brain to be targeted by DBS?
MJFF: Yes, new target areas are also being pursued. DBS pioneer Andres Lozano, MD, PhD spoke to us about some of these advances last year. He explained:
We are now moving forward with research into DBS treatments that might begin to treat non-motor symptoms of the disease. Traditionally, these symptoms are unresponsive to surgery. But there are different circuits in the brain, and each has its own unique job to do. Some are for tremor, some deal with rigidity, for example. Others regulate cognition and depression. We now believe that if we focus on specific circuits, we can isolate treatment for more specific symptoms. It’s like if you took your car in to get repaired — just because you need a new muffler doesn’t mean you also need to fix the engine. And even if you did, you wouldn’t expect the same procedure to fix both parts of the car.
We are now analyzing areas of the brain which are involved in generating non-motor symptoms. Traditionally, DBS targets the subthalamic nucleus. One of these new targets is the pedunculopontine nucleus (PPN), which could specifically address posture and balance, symptoms that traditionally do not respond to DBS. As of this conversation (October 2011), 100 patients in the world have undergone this procedure, and many centers are investigating the safety and efficacy of stimulating these areas of the brain.
What is the latest research on caffeine as a target to treat PD?
MJFF: Some researchers investigating the possible parkinsonian role of a brain chemical called adenosine are turning to coffee as a potential therapy for PD. Studies have shown that caffeine may block specific adenosine receptors which scientists believe may be overactive in PD. Blocking their activity could lead to higher levels of dopamine in the brain, which could, in turn, improve motor function in people with PD. Studies focused on adenosine and PD are picking up steam: Just this month, two companies reported positive clinical results into drug compounds that target the chemical.
And at this year’s PD Therapeutics Conference, Jeffry Stock, PhD, of Signum Biosiences explained how his company is targeting a certain cellular process that they believe leads to the clumping of alpha-synuclein in the brains of people with PD. By enhancing the activity of a protein called PP2A, researchers hope they might be able to prevent this clumping. Stock believes that a particular compound found in coffee might help to enhance PP2A activity, and researchers have begun to study doses of a decaffeinated brew for its effects in preventing this alpha-synuclein aggregation.
Is the Barratt Impulsiveness Scale Test used to diagnosis Parkinson’s disease?
MJFF: The Barratt test is not used to diagnose PD. For now, diagnosis is made by clinical examination during which a physician looks for two or more of the cardinal signs of PD (resting tremor, slowness of movement, and rigidity) to be present. The Fox Foundation continues to support the search for a biomarker for PD to provide an objective test for PD, which would go a long way toward earlier diagnosis, and earlier treatment for people with PD.
There is, however, research tying PD to Impulse Control Disorder (ICD). One study from Daniel Weintraub, MD, found that Parkinson's itself does not confer a higher risk for ICD, supporting other research that suggests the high prevalence of ICD in people with PD is actually related to Parkinson's medications, and not the disease itself.