Using Ultrasound Waves to Treat Parkinson’s Disease

Using Ultrasound Waves to Treat Parkinson’s Disease

By Leon Yang

For many suffering from the debilitating effects of Parkinson’s Disease, the idea of a cure seems abstract and unattainable. However, as Brian P. Mead, a scientist in the Department of Biomedical Engineering at the University of Virginia, has shown, treatment using ultrasound waves might pave the way for developing a noninvasive and effective cure for Parkinson’s disease.

In a May 2017 paper published in Nano Letters, Mead outlines a unique approach to treating Parkinson’s Disease in mice models. By using magnetic resonance image-guided focused ultrasound (FUS), Mead demonstrated that there is an efficient delivery of particles containing DNA that induce the production of important proteins that could help protect degenerating neurons and even induce them to regenerate.1

Parkinson’s disease is a serious neurodegenerative disease that affects around 2% of those over 65. It is associated with the degeneration of dopamine-producing neurons and has recently been categorized as a potential autoimmune disease in which a patient’s immune system will destroy the body’s neurons.2 Dopamine is a neurotransmitter that is best known for being associated with pleasure senses, but it also plays an integral role in motor control of the body.3 As such, symptoms of Parkinson’s disease include tremors in the hand, stiffness of gait, and dementia in advanced stages.4

Currently, there is no cure for Parkinson’s disease, and most treatments focus on slowing the progression of symptoms rather than reversing them. Other treatments such as deep brain stimulation are invasive surgical procedures that are risky, especially for patients who are still early in their progression of symptoms.5 Furthermore, the blood-brain barrier, a series of cellular junctions that isolates the brain from circulating blood in nearby capillaries, is impassable by most large molecules, excluding possible drug candidates that are administered through the veins.6

In his study, Mead outlines a unique approach to treating Parkinson’s Disease in mouse models. By using magnetic resonance image-guided focused ultrasound (FUS), Mead demonstrated an efficient delivery of particles containing DNA that induce the production of important proteins that could help protect degenerating neurons and even induce them to regenerate.1 The technique uses thermal images of the body to direct ultrasound waves–sound waves with frequencies too high for humans to hear–to allow these particles to diffuse into otherwise impassable regions of the brain

To circumvent these difficulties, Mead and his team decided to use ultrasound waves, waves with a higher frequency than sound waves audible to people, in order to make the blood-brain barrier permeable to beneficial drugs. Mead used nanoparticles carrying plasmids (small rings of DNA) and delivered them to targeted regions of the brain. These particles, called glial cell-line derived neurotrophic factors (GDNF), induced the production of GDNF proteins, which protect neurons.1

The combination of targeted ultrasound and GDNF produced very promising results in mouse models. Mice who received this treatment had greater amounts of the GDNF protein, greater levels of dopamine, and even greater concentrations of dopaminergic neurons striatum, a region in the forebrain. In addition, mice who received the treatment had better locomotion than mice who did not receive the treatment.1

A few aspects of Mead’s research are particularly exciting. Firstly, his work provides an effective and non-invasive treatment for Parkinson’s disease using an elegant method of using ultrasound waves. In addition, this treatment can be used to target specific parts of the brain, which is extremely important to reduce side effects on off-target regions. Moreover, a low concentration of the drug can be used to effectively treat Parkinson’s models in mice; this reduces the risk of toxicity in the brain, an important danger to consider during treatment.

Although Mead’s research is promising, it does have its limitations. Any successful model in mice may not be successful in humans. Other models of Parkinson’s Disease have even refuted the ability of GDNF to protect neurons.7 However, Mead’s treatment has already been FDA approved to be tested in individuals with Essential Tremor, a disease characterized with similar involuntary tremors as Parkinson’s Disease.1

Mead’s research demonstrates our ability to discover creative solutions to serious problems. Before, the prospect of a successful Parkinson’s Disease treatment seemed hard to fathom. Perhaps in the near future, with research like Mead’s, we will be able to provide the scientific community and patients with Parkinson’s Disease with an effective and noninvasive treatment to their symptoms.

References:

  1. Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores Dopaminergic Neuron Function in a Rat Parkinson’s Disease Model. Brian P. Mead, Namho Kim, G. Wilson Miller, David Hodges, Panagiotis Mastorakos, Alexander L. Klibanov, James W. Mandell, Jay Hirsh, Jung Soo Suk, Justin Hanes, and Richard J. Price Nano Letters 2017 17 (6), 3533-3542 DOI: 10.1021/acs.nanolett.7b0061
  1.  T Cells From Patients With Parkinson’s Disease Recognize α-Synuclein Peptides. D Sulzer et al. Nature 546 (7660), 656-661. 2017 Jun 21.
  1. Chinta S. J., Andersen J. K. (2005) Dopaminergic neurons. Int. J. Biochem. Cell Biol. 37:942–946.
  2. Jankovic J Parkinson’s disease: clinical features and diagnosis Journal of Neurology, Neurosurgery & Psychiatry 2008;79:368-376.
  3. Deep-Brain Stimulation for Parkinson’s Disease Study G. Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N Engl J Med. 2001;345(13):956–63. pmid:11575287.
  4. Sage MR, Wilson AL. The blood-brain barrier: an important concept in neuroimaging. AJNR Am J Neuroradiol 1994; 15:601-622. Medline
  5. Jolesz, Ferenc A. “MRI-Guided Focused Ultrasound Surgery.” Annual review of medicine 60 (2009): 417–430. PMC. Web. 27 July 2017.
  6. Decressac, M.; Ulusoy, A.; Mattsson, B.; Georgievska, B.; Romero-Ramos, M.; Kirik, D.; Björklund, A. Brain 2011, 134, 2302−2311.