Senior investigator, Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke

Daniel Reich, MD, PhD

“[We should] transcend our little categories: I work on MS; they work on Alzheimer. No, we have to really understand the ways in which brain tissue could be damaged. There probably aren’t an infinite number of ways and they're probably shared across diseases. So, I think it's a tremendously exciting time to be able to open up this field and for new researchers at the beginning of their careers to go into this. I think there's a lot we're going to learn in the next few years.”

A new phase 2a clinical trial paradigm consisting of 2 open-label studies studying 

 effects on 7-Tesla magnetic resonance imaging (7T MRI) paramagnetic rim lesions (PRLs) in multiple sclerosis (MS) is underway. The studies were presented at the 

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum

, February 25-27, by Jemima Akinsanya, DO, Neuroimmunology Clinical Fellow, National Institutes of Health (NIH).

Akinsanya and colleagues are researching the chronic and acute inflammatory properties of PRLs and are looking closely at the role of microglia in these lesions. Anakinra was approved by the FDA for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease in 2001, and tolebrutinib is an investigational, orally available, brain-penetrant Bruton’s tyrosine kinase inhibitor.

 spoke with a principal investigator of the study, Daniel Reich, MD, PhD, senior investigator, National Institutes of Neurological Disorders and Stroke, NIH, to learn more about microglia and its shared role in MS as well as other neurodegenerative diseases. He stressed the need to look at brain damage comprehensively across diseases and spoke about the growing opportunities for research in this cross-sectional field.

For more coverage of ACTRIMS Forum 2021, 

1. Akinsanya J, Absinta M, Dargah-zade N, et al. Toward the use of paramagnetic rim lesions in proof-of-concept clinical trials for treating chronic inflammation in multiple sclerosis. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Poster P126.
2. Kineret® (anakinra) for injection, for subcutaneous use. FDA. 2012. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103950s5136lbl.pdf

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The senior investigator at the National Institutes of Neurological Disorders and Stroke spoke about new opportunities for research into brain lesions and microglia. 

Microglia’s Role in MS and Other Neurodegenerative Diseases: Daniel Reich, MD, PhD

“I'm particularly excited about some of the new genomic tools for understanding cellular and molecular pathology and relating that to the imaging. One of the big efforts in our lab is to try to understand the cellular diversity. There are dozens of different kinds of cells with different flavors that are present in these lesions, and we're beginning to unravel that, and that is turning up new targets that we didn't necessarily expect.”

Anakinra (NCT04025554) and tolebrutinib are being studied for their effects on 7-Tesla magnetic resonance imaging (7T MRI) paramagnetic rim lesions (PRLs) in multiple sclerosis (MS) in 2 open-label studies.

 The studies, part of a new phase 2a clinical trial paradigm, were presented at the 

Akinsanya and colleagues are looking at PRLs for their chronic and acute inflammatory properties, and the new paradigm serves as a way to evaluate anakinra and tolebrutinib, but also the clinical trial design of using 7T MRI in MS. Anakinra was approved by the FDA for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease in 2001, and tolebrutinib is an investigational, orally available, brain-penetrant Bruton’s tyrosine kinase inhibitor.

 spoke with a principal investigator of the study, Daniel Reich, MD, PhD, senior investigator, National Institutes of Neurological Disorders and Stroke, NIH, to learn more about the evaluating clinical trial design of the trials he is working on. He also spoke about further research in the mechanisms of MS and finding new therapeutic targets.

For more coverage of ACTRIMS Forum 2021, click 

The senior investigator at the National Institutes of Neurological Disorders and Stroke spoke about further research his lab is conducting into MS mechanisms. 

Finding New Therapeutic Targets in MS: Daniel Reich, MD, PhD

“I think that the future of MS therapy is to begin to address not just the mechanisms by which new relapses occur, but also the mechanisms by which brain tissue at risk of deterioration goes bad.”

The effects of anakinra (NCT04025554) and tolebrutinib on paramagnetic rim lesions (PRL) in multiple sclerosis (MS) are being evaluated with the use of 7-Tesla magnetic resonance imagining (MRI) in 2 new open-label studies. The 2 studies are part of a new phase 2a clinical trial paradigm presented at the 

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021

, February 25-27, by first author Jemima Akinsanya, DO, neuroimmunology clinical fellow, National Institutes of Health (NIH).

Anakinra, approved by the FDA for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease in 2001, is a recombinant human interleukin-1 receptor antagonist.

 Tolebrutinib is an investigational, orally available, brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor. The study for anakinra is underway while the study for tolebrutinib is currently enrolling.

 spoke with Akinsanya and Daniel Reich, MD, PhD, senior investigator, National Institutes of Neurological Disorders and Stroke, NIH to learn more about how the treatments could benefit MS care. They also spoke about the importance of understanding MS mechanisms in the brain and being able to help patients with stable MRIs but clinically progressing disease courses.

1. Akinsanya J, Absinta M, Dargah-zade N, et al. Toward the use of paramagnetic rim lesions in proof-of-concept clinical trials for treating chronic inflammation in multiple sclerosis. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Poster P126.
2. Kineret® (anakinra) for injection, for subcutaneous use. FDA label. Updated December 2012. Accessed March 31, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103950s5136lbl.pdf

The duo from the National Institutes of Health discussed how monitoring and treating paramagnetic rim lesions can improve patient care in multiple sclerosis. 

Understanding Mechanisms of MS Chronic Inflammation: Jemima Akinsanya, DO, and Daniel Reich, MD, PhD

“There are some places, like specialty MS clinics, where the 7-T is used as the primary MRI scan for the patients in that clinic. And I imagine that if we see that 7-T really offers a much better look at the imaging features of relevance to patients then that usage will grow over time. And this is one area where that might be the case.”

A new phase 2a clinical trial paradigm using 7-Tesla magnetic resonance imagining (MRI) to evaluate 

paramagnetic rim lesions (PRL) in multiple sclerosis

 The 2 open-label studies investigating anakinra (NCT04025554) and tolebrutinib were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021, February 25-27, by first author Jemima Akinsanya, DO, neuroimmunology clinical fellow, National Institutes of Health (NIH).

Anakinra was approved by the FDA for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease in 2001.

 It is a recombinant human interleukin-1 receptor antagonist, and its study is underway. Tolebrutinib is an investigational, orally available, brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor and its study is currently enrolling.

 spoke with Akinsanya and Daniel Reich, MD, PhD, senior investigator, National Institutes of Neurological Disorders and Stroke, NIH to learn more about their investigations as well as the use of 7-Tesla MRIs in research and clinical practice. They discussed the potential of the technology and future usage.

The duo from the National Institutes of Health discussed the advantages of the ultra-high resolution imaging technology in research. 

7-Tesla MRI Use in Research: Jemima Akinsanya, DO, and Daniel Reich, MD, PhD

“We really have 2 goals here. One is obviously to try to treat this chronic inflammation and promote lesion repair. But, secondly, it's to use these trials to understand the biology so that the next trial we do, [either] the third one or a trial somebody else does, will be better and more focused with better outcome measures.”

Two open-label studies are underway to evaluate the effects of anakinra (NCT04025554) and tolebrutinib on 7-Tesla magnetic resonance imaging 

These studies, part of a new phase 2a clinical trial paradigm, were presented at the 

Approved by the FDA for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease in 2001, anakinra is a recombinant human interleukin-1 receptor antagonist.

 Tolebrutinib is an investigational, orally available, brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor. 

 spoke with a principal investigator of the study, Daniel Reich, MD, PhD, senior investigator, National Institutes of Neurological Disorders and Stroke, NIH, to learn more about the potential of anakinra and tolebrutinib in treating chronic inflammation in MS. He additionally outlined the details of the 2 studies that make up the new paradigm.

1. Akinsanya J, Absinta M, Dargah-zade N, et al. Toward the use of paramagnetic rim lesions in proof-of-concept clinical trials for treating chronic inflammation in multiple sclerosis. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Poster P126.
2. Kineret® (anakinra) for injection, for subcutaneous use. FDA. 2012. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/103950s5136lbl.pdf

The senior investigator at the National Institutes of Neurological Disorders and Stroke outlined studies on anakinra and tolebrutinib as part of a new phase 2a clinical trial paradigm.  

Understanding Chronic Inflammation in MS: Daniel Reich, MD, PhD

“The chronic inflammation is driven probably both by lymphocytes, T and B cells, which really drive the acute inflammation, but also by the innate immune cells, and particularly the innate immune cells of the brain microglia. So, we've been thinking about which therapies might modulate the activation of those cells, and the mechanisms they use to damage brain tissue.”

The effects of anakinra (NCT04025554) and tolebrutinib on 7-Tesla magnetic resonance imaging paramagnetic rim lesions in multiple sclerosis (MS) are being evaluated in a new 

 The 2 open-label studies were presented at the 

Anakinra, a recombinant human interleukin-1 receptor antagonist, was approved by the FDA for the treatment of rheumatoid arthritis and Neonatal-Onset Multisystem Inflammatory Disease in 2001.

 Tolebrutinib, on the other hand, is an investigational, orally available, brain-penetrant Bruton’s tyrosine kinase (BTK) inhibitor. 

 spoke with a principal investigator of the study, Daniel Reich, MD, PhD, senior investigator, National Institutes of Neurological Disorders and Stroke, NIH, to learn more about anakinra and tolebrutinib’s mechanisms of action and potential in MS. He stressed that while many therapies are available for central nervous system acute inflammation in MS, further investigation is needed to understand chronic inflammation’s role in the disease. 

The senior investigator at the National Institutes of Neurological Disorders and Stroke discussed 2 treatments currently being evaluated for use in multiple sclerosis. 

Daniel Reich, MD, PhD

Articles

Microglia’s Role in MS and Other Neurodegenerative Diseases: Daniel Reich, MD, PhD

Finding New Therapeutic Targets in MS: Daniel Reich, MD, PhD

Understanding Mechanisms of MS Chronic Inflammation: Jemima Akinsanya, DO, and Daniel Reich, MD, PhD

7-Tesla MRI Use in Research: Jemima Akinsanya, DO, and Daniel Reich, MD, PhD

Understanding Chronic Inflammation in MS: Daniel Reich, MD, PhD

Anakinra and Tolebrutinib for Chronic Inflammation in MS: Daniel Reich, MD, PhD

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