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President’s Letter:

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Scott Johnson, Myelin Repair Foundation President, CEO and Founder … waiting for a cure since 1976

Dear Friends and Supporters of MRF,

I have an important update to share with you: Based on data from our investigations to date and counsel from our advisors, we are dedicating our next fiscal year (which started July 1) to research on extracellular vesicles (EVs). EVs are a promising area that, while recently exploding in cancer research, have not yet been exploited in neurological diseases, like MS. Yet early research indicates that EVs may play a role in myelin formation.

The path that led us to this new focus is an important one, and it illuminates we why we are so excited.

A brief recap of our recent work

Beginning in 2017, MRF defined and funded a diverse group of projects with the long-term goal of finding quantifiable biomarkers of remyelination/repair in MS.

  • We funded 7 projects that focused on soluble markers (using blood, CSF or cell culture) of CNS biology that have the potential to be measured accurately in blood.
  • We funded 6 projects that used novel advanced imaging methods that should be translatable for use in clinical trials.

Our focus on MS patients

We decided at the outset to focus on MS patients and human cells because in vitro and animal study results don’t always correlate or translate to humans. Our short-term goals were to:

  • Generate wider interest in the identification of repair biomarkers
  • Encourage thinking beyond imaging only
  • Demonstrate leadership and innovation in the identification of repair biomarkers

We have made significant progress on all of these initial goals.

To see the potential impact of our focus this coming year, it’s important to understand the cells in the brain, and extracellular vesicles (EVs).

Cells in the brain

The five major types of cells in the brain shown in the graphic below each have distinct and critical functions:

  • Neurons – Receive and transmit synaptic signals
  • Oligodendrocytes – Myelinate / protect neurons
  • Astrocytes – Feed neurons and oligodendrocytes AND respond to local environment and communicate with all CNS cells
  • Microglia – Respond to the local environment and communicate with all CNS cells AND clear cellular debris and dead neurons in the CNS
  • Brain endothelial cells – Form Blood Brain Barrier
Diagram of Cells in the Brain

In order to maintain a healthy environment in the brain, there needs to be a “positive conversation” among the various CNS cells. However, in people with MS, it appears that there is a CNS environment that is non-permissive for recovery and repair.

With this in mind, our experiments are designed to answer questions like:

  • What molecules mediate this conversation?
  • How is this conversation altered in the context of disease?
  • How can molecules that indicate myelin damage or repair be collected and analyzed?

Extra cellular vesicles

Extracellular vesicles (EVs) are attracting considerable interest in the scientific community due to their role in intercellular communication. Within the nervous system, EVs have been proposed to participate in myelin formation as well as neurite outgrowth and neuronal survival. There are two major subcategories of EVs – Exosomes and Microvesicles (typically approximately four times as large as Exosomes).

This graphic illustrates cell/cell communication via EVs. The specificity of the cell/cell communication is likely restricted to particular cell types depending on many factors.

Diagram of cells in the brain: cell/cell communication via EVs.

MRF focus

This brings us to our current focus on biofluids, and specifically examining EVs. One of our funded collaborations with Jennifer Linden’s lab at Weill Cornell Medical College has generated preliminary data that indicates:

  1. EVs from CNS cells (in this case endothelial cells) can be isolated from human blood in sufficient quantities for analysis.
  2. The level of EVs in MS patients with active MS is much higher than in patients whose MS is not active or in healthy controls
  3. Some of the EV markers appear to distinguish active MS from stable MS as well as from healthy controls.

Thus we are very excited and optimistic about our next round of experiments focusing on EVs from all the CNS cell types (neurons, oligodendrocytes, astrocytes, microglia, and brain endothelial cells) – again always working with human samples.

Your help is essential

We have raised 80% of the funds we estimate are necessary to complete our five year initiative to identify at least one repair biomarker. We need your help with donations to close our funding gap so we can accomplish our ultimate goal of a world where MS no longer causes disability and disruption to millions in the prime of their lives.

Sincerely,

Scott

Focus on Biomarkers

The Myelin Repair Foundation is identifying biomarkers to help accelerate myelin repair treatments. Learn more about the importance of biomarkers and the role they play in getting treatments to patients.