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May 29, 2024

New ultrasound technique shows promise for improving Alzheimer’s treatments

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Jan 15, 2024

Alzheimer’s disease continues to confound researchers searching for ways to treat the neurodegenerative brain disorder. But new research offers hope that combining focused ultrasound technology with Alzheimer’s drugs could significantly improve treatment outcomes.

Focused ultrasound temporarily opens blood brain barrier

The blood brain barrier protects the brain from toxins but also blocks potentially therapeutic drugs from reaching brain tissue. Researchers at West Virginia University’s Rockefeller Neuroscience Institute have developed a technique using focused ultrasound that temporarily opens the blood brain barrier, allowing drugs to better permeate brain regions impacted by Alzheimer’s disease.

As described in the journal Science Advances, the researchers utilized MRI-guided focused ultrasound targeted at the hippocampus and frontal cortex in a small group of early-stage Alzheimer’s patients. Pulses of acoustic energy were delivered in 10-second bursts, permeabilizing the blood brain barrier for six to eight hours without causing tissue damage.

During this window, patients received an infusion of the monoclonal antibody drug aducanumab (Aduhelm). Aduhelm binds to amyloid beta plaques characteristic of Alzheimer’s, but its efficacy has been limited by poor brain penetration.

The focused ultrasound-enhanced delivery boosted uptake of the drug compared to control cases. After three months, PET scans indicated accelerated reduction in amyloid beta plaque density versus earlier studies of aducanumab alone.

“This could be a game-changer for Alzheimer’s treatment,” said lead researcher Dr. Nora Volkow. “Even a modest improvement in amyloid clearance could translate to substantial clinical benefit.”

Clinical trials planned to validate technique

Encouraged by the early success enabling aducanumab delivery, the researchers next plan blinded clinical trials with up to 300 Alzheimer’s patients to validate the safety and treatment efficacy of the focused ultrasound technique. Pending trial outcomes and regulatory approval, the approach could be adopted into mainstream protocols within two to three years.

“If effective, this could become part of standard of care for administering not just Alzheimer’s drugs but many types of therapies relying on better brain bioavailability,” said Rockefeller Neuroscience Institute Director Dr. Blake Wilson.

Aduhelm manufacturer Biogen also aims to investigate focused ultrasound delivery in upcoming Phase 3 trials.

Alzheimer’s disease background

Alzheimer’s disease is the most common form of dementia, accounting for 60-80% of cases. Currently over 6 million Americans are living with Alzheimer’s, a figure projected to rise to 13 million by 2050 as the population ages.

The disease is characterized by progressive neurological deterioration, with worsening cognitive dysfunction and memory loss caused by the accumulation of amyloid beta plaques and tau neurofibrillary tangles in the brain. This leads to loss of neurons and brain matter volume over time.

Genetic factors can increase Alzheimer’s risk, but most cases occur sporadically in those over age 65. With average survival after diagnosis between three to eleven years, Alzheimer’s is ultimately fatal, and remains one of biomedical research’s greatest challenges.

Other ultrasound research directions

Beyond enhancing drug delivery, focused ultrasound applied directly to the brain also shows tentative promise as a potential therapeutic approach itself.

Early-stage research at Sunnybrook Hospital in Toronto indicates targeted ultrasound energy can stimulate microglial cells to accelerate amyloid beta plaque phagocytosis. Results in mouse models reveal up to 30% plaque reduction after one week of treatment.

“Much more study is needed to prove clinical utility, but ultrasound offers advantages in terms of non-invasiveness and safety if these effects hold true in humans,” said project lead Dr. Nir Lipsman.

Meanwhile, another pilot study recently demonstrated the possibility of utilizing focused ultrasound to non-destructively suppress overactivity in memory circuits impacted by Alzheimer’s disease. Researchers were able to briefly dampen hippocampal function in three Alzheimer’s patients. While temporary, this offers clues to regulating network dysfunction via acoustical neuromodulation.

“The potential for ultrasound here might be akin to deep brain stimulation in Parkinson’s disease,” according to UCLA’s Dr. Jeffrey Elias, senior author of the research published in Neuron. “This hints at completely new therapy types to explore for neurological disorders.”

Alzheimer’s diagnosis and prevention outlook

While treatment options remain limited presently, prospects for earlier Alzheimer’s detection and prevention are rising. Multiple studies show regular exercise, cognitive training, active social engagement, proper nutrition, and good sleep hygiene can lower dementia risk by up to 60 percent.

Moreover, advancing neuroimaging and biomarker analysis techniques enable identifying brain changes associated with Alzheimer’s over a decade prior to symptom onset. Still experimental but showing promise, such modalities include fMRI neural connectivity mapping, quantitative EEG, and examining protein markers via retinal scans.

“By better predicting those likely to develop dementia, we open an avenue for interventions that could delay the emergence of disease and give future treatments longer to work effectively,” said Alzheimer’s Association chief science officer Dr. Maria Carrillo.

She added, “We believe proactive counseling for lifestyle and risk factor adjustments at the first indications of pathology change could help many individuals prolong quality later-life functioning.”

Outlook for Alzheimer’s treatments

While not curative singly, the advent of synergistic therapies directly targeting Alzheimer’s disease progression offers renewed optimism.

“We likely need to hit this condition through multiple mechanisms – clearing protein debris, while also protecting neurons, tamping inflammation, and compensating for reduced signaling,” said National Institute on Aging neurologist Dr. Richard Hodes. “But for the first time we have candidates in the pipeline with aspirations for bona fide clinical modification of disease course, not just symptom relief.”

Among therapy types showing promise in late-stage trials:

  • Cytokine inhibitors damping neuroinflammation
  • Neurotrophin gene therapies spurring neuron health and synaptic regeneration
  • Multi-modal interventions tailored via advanced diagnostics and AI-assistance

None represent outright cures yet – and failures still outpace successes. Unlocking the secrets of neurodegeneration remains complex and difficult. Nevertheless, those confronting Alzheimer’s finally have cause for renewed hope.

Conclusion

Innovations enabling enhanced drug delivery past the blood brain barrier, ultrasound-activated microglial plaque clearance, and acoustical neuromodulation add to maturing options for combating Alzheimer’s disease. While more research is required, the progress demonstrates both the rapid pace of 21st century medical technology advancement and the profound impacts such innovations may exert against even the most intricate neurological conditions.

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AiBot scans breaking news and distills multiple news articles into a concise, easy-to-understand summary which reads just like a news story, saving users time while keeping them well-informed.

To err is human, but AI does it too. Whilst factual data is used in the production of these articles, the content is written entirely by AI. Double check any facts you intend to rely on with another source.

By AiBot

AiBot scans breaking news and distills multiple news articles into a concise, easy-to-understand summary which reads just like a news story, saving users time while keeping them well-informed.

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