Focused Ultrasounds and Alzheimer’s Disease
by Sitarah Zemar
Background
Recently, researchers at WVU have partcipated in a newfound means of treating patients with Alzheimers. Their clinical trail focus exhibited the use of ultrasound technology to open the blood brain barrier of patients with Alzheimer’s disease. In the past, Alzheimers disease has been shown to result in a cognitive decline where only the symptoms are treatable. This is partly due to the protective layer of cells, the blood brain barrier, that lines the brain and protect the toxins and medications from reaching the brain. With 6 patients in early stages of Alzheimer’s WVU scientists were able to test the safety, longevity and effectiveness of the ultrasound in aiding the deliverance of drugs to their brain.
Behind Alzheimer’s
Beta-amyloid will attack the connection between the brain’s nerve cells, resulting in less synapses. The current drugs target the overproduction of this beta-amyloid and focus on slowing it. Researchers at the Institute of Psychiatry believe that once the synapses have been destroyed it causes an influx of more protein beta-amyloid to be produced. Overall, the process feeds into a negative feedback loop that perpetuates memory loss and dementia.
Focused Ultrasound
It has recently been proposed that focused ultrasound technology can target deep parts of the brain without causing harm to the rest of the surrounding, normal tissue. The beams provide a means to targeting an area without any invasive techniques, while microbubble intrafusion can increase permeability of the blood-brain barrier by propagating the beam.
There have been previous issues with creating drugs that are able to sufficiently cross the blood-brain barrier and diffuse the drugs or toxins. With this newfound way to use ultrasounds, they enable a better means for delivery of anti-amyloids to the brain. According to studies, ultrasound can reduce Beta-amyloid plaque and improve cognition in animals with Alzheimer’s disease.
The Results
Ultimately found that FUS treated transgenic mice exhibit reduced hippocampal Beta-amyloid plaque. They also saw that one FUS treatment can reduce the existing plaques 2 days to 2 weeks after they have been targeted. When treatment is induced at two-week intervals there was found to be a cumulative effect in order to reduce the Beta-amyloid plaques. The FUS induced activation of microglia that add to the decrease in plaque size with their high mobility.
It was also proposed that FUS creates a means for immune cells to enter the brain and to aid in clearance. FUS treatments have opened possibilities for reducing plaque, memory deficits and increasing neurogenesis. After the proposed work, the field needs a focus on what pharmacological agents would be best paired with FUS in reducing inflammation and finding the mechanisms that drive the pathogenesis.
Potential advanatges from repeated treatment with ultrasound:
- minimizes damage to non-targeted healthy tissue
- non-invasive and reduces risk for infections and blood clots
- can enhnace drug therapies by modifying the blood-brain barrier
Sources
King’s College London. “Discovery could explain failed clinical trials for Alzheimer’s, and provide a solution.” ScienceDaily. ScienceDaily, 19 September 2018. <www.sciencedaily.com/releases/2018/09/180919200332.htm>.
Poon CT, Shah K, Lin C, Tse R, Kim KK, Mooney S, Aubert I, Stefanovic B, Hynynen K. Time course of focused ultrasound effects on β-amyloid plaque pathology in the TgCRND8 mouse model of Alzheimer’s disease. Sci Rep. 2018 Sep 19;8(1):14061. doi: 10.1038/s41598–018–32250–3.
