New Research Aims to Reverse Paralysis & Alzheimer’s Disease

But three Cedars-Sinai investigators are pioneering research in neurology to reverse damage: to re-engineer the body and restore movement and memory lost to disease or injury.

In this story, we visit their laboratories to explore early-stage studies that aim to help stroke survivors control prosthetic devices, repair spinal cord injuries and reverse cognitive decline.

Could Stroke Survivors Gain Better Control of Prosthetics?

The Challenge

A neuroprosthesis is a device, such as a robotic limb or brace, that can be controlled by thought. It’s designed to replace the function of a limb that’s been lost or paralyzed. Patients with robotic arms must have electrodes implanted in their brains to capture electrical signals and translate them into movement.

But since patients who have suffered a stroke often have injury to the motor cortex—which is most responsible for sending voluntary movement signals to muscles—they are often unable to operate a robotic limb. Additionally, the devices are slow, can require weeks of training and lack the sense of touch of a natural limb.

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The Progress

Research at Cedars-Sinai has found that leveraging new parts of the brain could improve patients’ control of these prosthetics. In a 2024 study, Cedars-Sinai’s investigators showed the cerebellum is also involved.

“When we stop the cerebellum from doing its work, we find that the motor cortex doesn’t function so well,” said Aamir Abbasi, PhD, a postdoctoral scientist and the first author of the study.  

In a subsequent study, Abbasi and colleagues found the cerebellum could operate a neuroprosthesis in animal models.

If a healthy cerebellum can be used instead of or in addition to other parts of the brain, many more stroke patients would be able to use neuroprosthetics. Combining signals from different parts of the brain might also improve neuroprosthetics’ speed and realism.

Could a Spinal Cord Heal Itself After an Injury?

The Challenge

A robotic brace can empower a patient with a paralyzed limb, but regaining the use of that limb would be the ultimate achievement.

Injured spinal cords seldom repair themselves because the body has a hard time regrowing and reconnecting axons, the long fibers that carry electrical signals from the brain to the body, and neurons, nerve cells in the brain and spine. But even when parts of the spinal cord are damaged, other parts remain healthy—and sometimes paralyzed patients can regain some feeling and movement in their extremities.

The Progress

A new Cedars-Sinai study, co-authored by Sarah McCallum, PhD, may provide clues to help the spinal cord heal itself.

“We’re trying to understand what’s going on in the cells of that healthy tissue to allow it to regenerate,” McCallum said. “So that maybe we can harness it to improve repair and get people with spinal cord injuries walking again.”

After lesion or injury to the spinal cord, the white matter that insulates the axons breaks up into fatty deposits. The nervous system sends in immune cells that often struggle to clear the debris, creating inflammation and scarring.

Astrocytes are star-shaped cells that support neurons. McCallum and colleagues discovered that a certain type of astrocyte located in healthy parts of the spinal cord, far from the lesion, reacts to try to help the struggling immune cells.

“These lesion-remote astrocytes release a protein called CCN1 that instructs the immune cells how to clean up the fatty deposits,” McCallum said.

CCN1 plays a similar role in other diseases, such as fatty liver disease and atherosclerosis, the fatty plaque deposits that can block arteries.

“If we can find a way to enhance and target these astrocytes and the immune cells they talk to, maybe we can help the body heal itself after one of these spinal cord injuries,” said McCallum.

Importantly, the group found that this same approach might also work to help patients suffering from other diseases that cause similar white matter damage, such as multiple sclerosis and white matter strokes.

Can the Effects of Aging in the Brain Be Reversed?

The Challenge

Neurons in the spinal cord can be injured in accidents or by disease. Similarly, neurons and immune cells in the brain can be slowed and damaged by age and conditions such as Alzheimer’s disease.

Past research has shown cognitive decline in older mice can be reversed by blood transfusions from young mice. A small clinical trial has shown this treatment can be safe and feasible in human Alzheimer’s patients, as well. But even if proven effective, treating all Alzheimer’s patients with blood from young donors would face significant practical challenges.

The Progress

A recent Cedars-Sinai study has reversed cognitive decline in mice using stem cells, which can be reprogrammed to become any cell in the body.

Alexandra Moser, PhD, and colleagues created an immune cell found in the blood called a mononuclear phagocyte. These immune cells patrol the body and respond to injury or disease by getting rid of anything foreign or broken—but they become defective with age or neurodegenerative disease.

“Using stem cells, we made young versions of these immune cells, and we administered them to mouse models of aging and Alzheimer’s,” said Moser. “We found the mice that received the cells performed a lot better in memory tests and showed improvements in brain health.

“We can make an unlimited number of these stem cells,” Moser said. “And the cells can be individualized—made from the patient—so there’s no risk of the patient’s immune system rejecting the transplanted cells.”

But Moser says there’s a lot more work to be done before the researchers will be ready to test this treatment in patients.

In the meantime, the team will continue to research what mononuclear phagocytes are doing to improve cognition and brain health.