Lymphatic brain vessels represent potential avenue for MS treatment

The lymphatic vessels, which clear harmful material from the brain, appear to carry previously unknown messages from the brain to the immune system that ultimately trigger disease symptoms for multiple sclerosis (MS), according to scientists at University of Virginia School of Medicine. Blocking those messages may offer doctors a new means to treat a potentially devastating condition that affects more than 2 million people.

The discovery comes from the lab of UVA researchers who identified the lymphatic vessels surrounding the brain (vessels that textbooks long insisted did not exist). In an exciting follow-up, the researchers have determined that these vessels play an important role not only in MS but, most likely, many other neuroinflammatory diseases and dangerous brain infections.

Commenting on the mechanism identified, researcher Antoine Louveau PhD, of UVA’s Department of Neuroscience and its Center for Brain Immunology and Glia (BIG), said: “Our data suggests that there is a signal coming from the brain to the lymph nodes that tells immune cells to get back into the brain, causing the [multiple sclerosis] pathology”.

“This is an important proof of principle that exploring the role of these vessels in different neurological disorders, including multiple sclerosis, is worth it.”

The researchers at UVA, led by Jonathan Kipnis PhD, were able to impede the development of MS in mice by targeting the lymphatic vessels surrounding the brain. They used multiple strategies to block the lymphatics or destroy them with a precision laser. All led to the same outcome: a decrease in the number of destructive immune cells capable of causing paralysis.

The message from the brain that appears to drive MS, however, remains poorly understood. The researchers can tell the message is being sent, and what the result of the instruction is, but they don’t yet know what mechanism the brain is using to send it. “I think the next step in this specific research is to identify what that signal is. Is it a cellular signal, is it a molecular signal?” Louveau said. “And then to try to target that signal specifically.”

The researchers noted that removing the vessels did not entirely halt multiple sclerosis, however, which suggests the impact of other factors – and more for scientists to explore.

UVA’s new research offers important insight into the function and role of the lymphatic vessels that connect the brain to the immune system. In most aspects, they work exactly as scientists would expect – just like other lymphatic vessels in the body.

“Meningeal lymphatic vessels are quite small compared to other lymphatics in the body, and we and others wondered if this might limit the amount and size of cargo they can pass through,” Herz said. “During inflammation, they did not change in size or complexity much, but what was really exciting to discover [was that] they allowed whole immune cells to traffic through them, and we found the molecular cues for that.”

However, the lab’s recent research also highlights the complexity doctors face when trying to manipulate the vessels to benefit human health. For example, blocking the vessels had a benefit in the MS model, but the lab has also shown that the vessels’ healthy function is vital to staving off Alzheimer’s disease and preventing the cognitive decline that comes with age.

That means that it’s unlikely that stopping MS could be as simple as blocking the flow inside the vessels. It also suggests that there is probably no single treatment approach that will work for every neurological disorder. However, the new-found significance of the vessels promises to offer doctors an exciting avenue for tackling neurological diseases.

“These findings on the role of brain-draining lymphatic vessels in MS, together with our recent work on their role in Alzheimer’s disease, demonstrate that the brain and the immune system are closely interacting. When these interactions go out of control, pathologies emerge,” said Kipnis, chairman of UVA’s Department of Neuroscience and director of the BIG Center. “The idea that we could target major neurological disorders through therapeutic manipulation of peripheral structures, such as lymphatic vessels, is beyond exciting. Through our collaboration with PureTech Health, we hope to bring these laboratory findings to improve patients’ lives one day.”