The Quest for Effective Stroke Recovery

Stroke remains a leading cause of long-term disability in the United States, affecting nearly 800,000 Americans each year, according to the Centers for Disease Control and Prevention (CDC). While physical rehabilitation is the cornerstone of stroke recovery, its effectiveness is often limited by the intensity and duration patients can sustain.For many stroke survivors, achieving a full recovery and regaining lost motor skills remains a meaningful challenge.

Now, a new study from UCLA Health offers hope. Researchers have identified a drug, known as DDL-920, with the potential to supplement and enhance rehabilitation efforts, perhaps leading to more significant and lasting improvements for stroke survivors.

The goal is to have a medicine that stroke patients can take that produces the effects of rehabilitation.

Dr. S. Thomas Carmichael, UCLA Neurology

dr. S. Thomas Carmichael, the study’s lead author and professor and chair of UCLA Neurology, emphasizes the need for advancements beyond traditional rehabilitation. Rehabilitation after stroke is limited in its actual effects becuase most patients cannot sustain the rehab intensity needed for stroke recovery. This highlights the crucial role that pharmacological interventions could play in augmenting and accelerating the recovery process.

Carmichael further notes the disparity between stroke recovery and other medical fields. Further, stroke recovery is not like most other fields of medicine, were drugs are available that treat the disease — such as cardiology, infectious disease or cancer. Rehabilitation is a physical medicine approach that has been around for decades; we need to move rehabilitation into an era of molecular medicine.

Unlocking the Brain’s Recovery Mechanisms

Published in Nature Communications, the UCLA study details how Carmichael and his team investigated the specific brain mechanisms through wich physical rehabilitation improves function after a stroke. Their research, conducted using laboratory mouse models of stroke and involving human stroke patients, pinpointed a critical phenomenon: stroke-induced loss of brain connections even in areas remote from the primary site of damage.

Specifically,the team discovered that stroke disrupts connections involving parvalbumin neurons,a type of brain cell crucial for generating gamma oscillations – brain rhythms that synchronize neuronal networks and facilitate coordinated movements. Stroke diminishes these gamma oscillations, impairing motor functions. however, successful physical rehabilitation was shown to restore gamma oscillations and repair lost connections in parvalbumin neurons in the mouse model. this suggests that boosting gamma oscillations could be a key therapeutic strategy.

Think of it like a marching band.If the drummer (parvalbumin neurons) loses rhythm, the entire band (brain networks) falls out of sync, and coordinated movement (gait, arm function) becomes challenging.Stroke disrupts the drummer’s ability to keep time, but rehabilitation can help them regain their rhythm.

DDL-920: A Promising Candidate

Based on their findings, the UCLA team identified two potential drugs that could stimulate gamma oscillations. One of these drugs, DDL-920, developed in the UCLA lab of Varghese john, demonstrated significant advancement in motor control in the mouse models. This is a crucial step, suggesting that DDL-920 could potentially mimic the beneficial effects of physical rehabilitation at a molecular level.

This discovery has two significant implications, according to the researchers: first, it identifies the brain structures and circuitry underlying the effects of rehabilitation. Second, it identifies a unique drug target within that circuitry that may promote recovery by mimicking the effects of physical therapy.

The Road Ahead: Clinical Trials and Future Possibilities

While the results are encouraging, it’s crucial to remember that DDL-920 is still in the early stages of development.As of March 2025, further research is necessary to fully understand its safety and effectiveness in humans before clinical trials can begin.

Potential counterarguments also need to be addressed. Some experts caution against overstating the potential of a single drug and emphasize the continued importance of comprehensive rehabilitation programs, including physical, occupational, and speech therapy. Concerns about potential side effects and long-term efficacy also need to be rigorously evaluated during clinical trials.

However, the potential benefits are substantial. If DDL-920 proves safe and effective in human trials, it could revolutionize stroke recovery, particularly for patients who struggle to achieve sufficient intensity or duration of traditional rehabilitation. Imagine a future where stroke survivors have access to a medication that helps them regain lost motor skills more effectively, allowing them to return to independent living and improve their quality of life. This is the hope that DDL-920 offers.