Marwan Sabbagh, MD

"If I could show any mechanism, a decent mechanism of action on a clinical signal, the companies that own this drug will probably take keen interest in it.”

 announced it had received 5-year grants from the National Institute of Aging (NIA) and the Alzheimer’s Drug Discovery Foundation (ADDF) to propel a study examining FDA-approved cancer drug lenalidomide in Alzheimer disease (AD). Led by Marwan Sabbagh, MD, and Boris Decourt, PhD, the dual study design will identify whether the drug can reduce inflammation and other disease-related neuropathological features, as well as improve cognition in those living with mild cognitive impairment (MCI).

Sabbagh, director of the Lou Ruvo Center for Brain Health and neurologist at Cleveland Clinic, noted that he has no proprietary stake in lenalidomide, but that if the drug is successful, industry leaders will swoon. Enthusiasm to study lenalidomide stems from the strategy to target multiple AD neuropathologies at once, a relatively new approach in AD drug development.

Sabbagh discussed the idea of whether repurposed drugs need more observation in the AD space, and the potential impact lenalidomide could have if proven successful.

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The director of the Lou Ruvo Center for Brain Health and neurologist at Cleveland Clinic discussed whether lenalidomide, a repurposed cancer drug, has promise as an Alzheimer disease DMT. 

Lenalidomide’s Outlook as Future Alzheimer DMT: Marwan Sabbagh, MD

"It has come and gone and come and gone, but now it’s coming back into vogue again. Not on the COX side, but on this other pathway. That’s appealing, right? Because it’s a targetable space.”

A recently initiated study will explore whether lenalidomide, an FDA-approved cancer treatment, can reduce inflammation and other disease-related neuropathological features in patients with mild cognitive impairment. Lenalidomide is among a number of multipurpose agents which have demonstrated several effects on the immune system in cancer patients, and in this case, comes with an already established safety and toxicity profile.

According to Marwan Sabbagh, MD, if the study is successful and shows any signal of anti-inflammatory approach, researchers will be quick to rush back into the inflammation research space. Sabbagh, director of the Lou Ruvo Center for Brain Health and Neurologist at 

, will be leading the project alongside his colleague Boris Decourt, PhD.

Sabbagh provided his thoughts on whether the success of lenalidomide will increase the number of Alzheimer disease clinical trials for other repurposed drugs that demonstrate inflammation reduction. He also answered questions on whether there is an appropriate range to which drugs can be observed.

The director of the Lou Ruvo Center for Brain Health and neurologist at Cleveland Clinic discussed the research opportunities for repurposed anti-inflammatory drugs for Alzheimer disease.

Repurposed Anti-Inflammatory Drugs in Alzheimer Disease: Marwan Sabbagh, MD

"The reason these omides are picked is because they have a dual mechanism of action that inhibits both TNF alpha and inflammation in the non-COX pathway, but also in the TNF alpha pathway. These also have potent effects on both amyloid and base.”

Lead investigators Marwan Sabbagh, MD, and Boris Decourt, PhD, were recently tasked with leading a study on assessing the therapeutic potential of the anti-cancer drug lenalidomide in early-stage Alzheimer disease (AD), or mild cognitive impairment. The project is comprised of 2 complementary clinical studies aimed at identifying whether the drug can reduce inflammation and other disease-related neuropathological features, as well as if it can improve cognition.

Sabbagh, director of the Lou Ruvo Center for Brain Health and neurologist at 

, noted that lenalidomide is the child of thalidomide, which was observed by Sabbagh and his colleagues in patients with AD over a decade ago but was not well-tolerated. However, the enthusiasm to observe lenalidomide in this patient population stems from the strategy to target multiple AD neuropathologies at once.

Sabbagh detailed the origins of the study, as well as why this drug may lend itself to positive results.

The director of the Lou Ruvo Center for Brain Health and neurologist at Cleveland Clinic provided an overview on how lenalidomide, an FDA-approved cancer drug, will be evaluated in Alzheimer disease. 

Evaluating Cancer Drug Lenalidomide in Alzheimer Disease: Marwan Sabbagh, MD

We went through a low of trudging along, and now we’re back to that new level of excitement. This is a very important watershed moment in our field.

As the Alzheimer disease (AD) community awaits the 

, the shift focuses back to the research, and continuing to increase the momentum the AD community has gained over the past decade. The hope is that If approved, aducanumab may create the domino effect for other treatments and expand the current landscape further.

For now, there still remain multiple unmet needs for patients withAD despite the growing knowledge of the disease. Marwan Sabbagh, MD, director of the Lou Ruvo Center for Brain Health and neurologist at Cleveland Clinic claimed that prevention of AD is the “sexy” option but is further away than people understand. He feels as though treatment options are more attainable and can ultimately make a greater impact now than focusing on prevention.

, Sabbagh makes his case for both prevention and treatment as the most pressing topics for the AD community. He also provides an outlook on future research and why other clinician communities should be buzzing more about aducanumab’s upcoming FDA decision.

The director of the Lou Ruvo Center for Brain Health and neurologist at Cleveland Clinic highlighted the most pressing needs within the Alzheimer disease community.

Marwan Sabbagh, MD: What’s the Greater Need in Alzheimer, Treatment or Prevention?

“We’re now seeing the real possibility of plasma biomarkers being deployed in clinical applications within the year.”

2020 Alzheimer’s Association International Conference

 (AAIC), there was a slew of promising presentations, including multiple studies that examined the use of blood biomarkers that can distinguish Alzheimer disease (AD) from other neurodegenerative disorders. P-tau217, among the more notable biomarkers, was found to be closely linked to a buildup of amyloid plaques in the brain as measured by positron emission tomography (PET) scan.

Marwan Sabbagh, MD, director of the Lou Ruvo Center for Brain Health and neurologist at Cleveland Clinic, is an acute observer of the research within the AD community. His biggest takeaway from last year’s AAIC meeting was the increased knowledge of lifestyle changes to reduce the risk of AD. This year, blood biomarkers were the main eye-catching observation, along with a few other discoveries.

, Sabbagh shared his overall thoughts and takeaways from AAIC 2020, including why blood biomarkers are a hot topic and something he plans to continue to look out for in future research.

The director of the Lou Ruvo Center for Brain Health and neurologist at Cleveland Clinic detailed the state of Alzheimer disease and what research particularly grabbed his attention  at AAIC 2020.

Marwan Sabbagh, MD: Observations From AAIC 2020

“The question obviously is, ‘does removing amyloid in clearance do enough?’ I don’t come away with the thought that these approaches are wrong. I just don’t know that we tested it correctly or answered it as well as we could.”

Aducanumab’s prescription drug user fee act action date of March 2021 acts as an immense weight on the Alzheimer disease (AD) community, as it aims to be the first approved drug to reduce clinical progression. Researchers truly do not know how AD research will change following an approval. Will there be an increased number of amyloid therapy drugs on the way, or will research efforts continue to be varied in nature, with blood biomarkers and lifestyle changes leading the charge?

Marwan Sabbagh, MD, feels as though there is still much work to be done with amyloid therapies, but is excited that aducanumab has “reinvigorated” the AD research community. Sabbagh, who is the director of the Lou Ruvo Center for Brain Health and neurologist at Cleveland Clinic, compared treating AD to HIV, claiming that the disease can be treated at different clinical progression points.

, Sabbagh explains where research efforts should turn to if aducanumab is approved, along with some of his takeaways on the current pharmacological menu of treatment options.

The director of the Lou Ruvo Center for Brain Health and neurologist at Cleveland Clinic discussed how Alzheimer disease research may change if aducanumab becomes approved.

Marwan Sabbagh, MD: How Aducanumab Impacts Future Studies

“This is a transformative moment. We are now about to take the journey toward transforming Alzheimer disease from a terminal disease as we know it, to a chronic disease.”

Biogen’s aducanumab made news again in early August after the FDA announced that it had accepted the biologics license application (BLA) with priority review, setting a Prescription Drug User Fee Act (PDUFA) target action date of March 7, 2021. Aducanumab, also known as BIIB037, would become the first treatment for reducing clinical decline in Alzheimer disease (AD) through its mechanism of selectively targeting aggregated forms of amyloid-beta, including both soluble oligomers and insoluble fibrils.

Marwan Sabbagh, MD, director, Lou Ruvo Center for Brain Health, and neurologist, Cleveland Clinic, understands the clinical importance of such an agent and the gravity of situation if the drug is approved. As an opinion leader in AD, Sabbagh feels as though the aducanumab can breed new life the AD research field while also proving that amyloid-targeting therapies can play a major role in controlling clinical decline.

, Sabbagh shared his excitement about the potential of aducanumab in this population, as well as provided information on why he supports the research of amyloid-targeting therapies.

The director of the Lou Ruvo Center for Brain Health and neurologist at Cleveland Clinic discussed the potential of aducanumab and the amyloid theory in patients with Alzheimer disease.