Parkinson’s disease (PD) is probably the most iconic neurological disorder. It has diverse manifestations, typical of many neurological diseases. PD is a result of brain dopamine deficiency, and its clinical picture is dominated by motor symptoms- tremor, rigidity and bradykinesia (slowing of movements). It however also manifests with a variety of non-motor symptomswhich rival the motor symptoms in their impact. PD is responsive to treatment with several oral medications such as levodopa, infusions such as apomorphine, and interventions such as deep brain stimulation (DBS).
Regardless of the intervention used, PD is a neurodegenerative disorder that grinds, slowly and steadily, along a chronic progressive course. This often manifests with disabling features such as freezing, hallucinations, and dyskinesias (drug-induced writhing movements). These symptoms creep or barge in unannounced, challenging the wits of the neurologist, and pushing the resolve of patients and their families to the limit. What hope does research offer to smooth the journey for people with PD? Here are my top 7.
1. Increasing evidence for the benefit of exercise
Dyskinesias are abnormal, fidgety movements that develop as side effects of the drugs used to treat PD. Most people with dyskinesias are not overly concerned about the movements because the alternative, disabling freezing and immobility, is worse. Dyskinesias are however energy-sapping, and are distressing for family members. Amantadine is one drug neurologists add-on to improve dyskinesias, but many people do not tolerate or benefit from this. The suggestion that lithium may help dyskinesias is therefore welcome news. The report comes from a study in mice reported in the journal Brain Research titled The combination of lithium and l-Dopa/Carbidopa reduces MPTP-induced abnormal involuntary movements (AIMs). A long way to go yet, but hope.
What a great thing, the blood-brain barrier, protecting the brain from all the bugs and toxins running amok in the bloodstream. This iron-clad fence unfortunately also effectively keeps out, or limits the entrance of, many beneficial drugs which need to get to the brain to act. As with all borders however, there are always people ready to break through, without leaving any tracks behind. And the people in this case are neurosurgeons who have successfully bypassed the blood brain barrier, and safely ‘transported’ PD drugs in to the brain. They did this by removing a portion of the blood brain barrier of mice, and replaced it with a piece of the tissue which lines the inside of the nose, a procedure called nasal mucosal grafting. They then delivered glial derived neurotrophic factor (GDNF), a protein that treats PD in mice, across the graft. The neurosurgeons explained all this in their paper titled Heterotopic mucosal grafting enables the delivery of therapeutic neuropeptides across the blood brain barrier. You may however prefer the simpler version from the Boston Business Journal (can you believe it!) titled A new way to treat Parkinson’s disease may be through your nose.It will however take time before human trials of nasal mucosal grafting…this is science after all, not science fiction!
6. Fetal stem cell transplantation
It doesn’t seem too long ago when all ethical hell broke loose because some scientists were transplanting fetal tissue into human brains. I thought the clamour had put this procedure into the locker, never to be resurrected. Apparently not; fetalstem cell transplantation (SCT) is back, reminiscent of Arnold Schwarzenegger in the Terminator films. Learn more of this comeback in this piece from New Scientist titled Fetal cells injected into a man’s brain to cure his Parkinson’s. The work is from Roger Barker‘s team at the University of Cambridge, and they are planning a big study into this named TRANSNEURO. Watch this space
7. Pluripotent stem cell transplantation
The future of stem cell transplantation probably lies with pluripotent, rather than fetal cells. The idea is to induce skin cells, called fibroblasts, to transform into dopamine-producing cells. Fibroblasts can do this because they are pluripotent cells; that is they are capable of becoming whatever type of cells you want, so long as you know the magic words. In this case, the words are likely to be the transcription factors Mash1, Nurr1 and Lmx1a. Beats ‘open sesame‘, and surely less controversial than fetal cells. Researchers are taking this procedure very seriously indeed, setting out ground rules in articles such as Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. This was publishedin the journal Nature, but you may prefer the easier read in New Scientist titled Brain cells made from skin could treat Parkinson’s. But don’t get too excited…pluripotent stem cell transplantation is barely at the starting line yet.
There is so much more going on in the field of Parkinson’s disease to cover in one blog post. I will review neuroprotection in Parkinson’s disease in a coming post. In the meantime, here are links to 12 interesting articles and reviews on the future of PD:
An odd connection you may say but here are quite a few things that link epilepsy with music. lepsy. The first is the therapeutic effect of on epilepsy. This has been termed ‘The Mozart Effect‘ based on studies which report that listening to Mozart reduces epileptic brain discharges.
This however seems at odds with the known fact that epilepsy may be triggered by music. Music is one of several triggers of epilepsy. People with this musicogenic epilepsy may become frightened of music, a concept called musicophobia. This article in Scientific American gives an example where the music of Sean Paul is the consistent trigger for someone’s seizures. In another anecdote from NME, a Ne Yo song is the culprit.
Finally, music may be a manifestation of epilepsy. These present as musical hallucinations.