HIV drug derivative shows MS potential

An experimental MS drug restored movement and vision in mice by protecting nerve fibres and myelin, researchers report.

The treatment, called K-9, also prevented increases in neurofilament light chain, a blood marker of nerve damage often used in clinical trials.

Mice treated with the approved multiple sclerosis drug fingolimod did not show the same reversal of symptoms.

The research was led by Jayakrishna Ambati at the University of Virginia School of Medicine and focused on experimental compounds known as kamuvudines.

Ambati said: “The reversal of disease was surprising. We expected K9 might protect animals from getting worse.

“We didn’t expect animals that were already impaired to bounce back completely, both in their movement and their vision.”

The compounds were developed from nucleoside reverse transcriptase inhibitors, or NRTIs, a class of drugs used against HIV.

Previous work by the researchers found that people taking NRTIs had a much lower risk of developing macular degeneration. Further investigation suggested the drugs block inflammasome activation, a process involved in inflammation.

Because NRTIs can have serious toxicities, the team developed kamuvudines designed to block inflammasomes without the harmful side effects associated with the older drugs.

In the mouse model of MS, K-9 protected spinal cord nerve fibres and myelin, the protective insulation around nerves that is damaged in multiple sclerosis.

Animals that already had impaired movement and vision recovered those functions after treatment, the researchers reported.

Ambati said: “It was dramatic to see an animal that couldn’t use its legs or see properly recover that function completely.”

The researchers believe K-9 works by blocking interactions between proteins that join together to create inflammasomes and trigger inflammation.

Ambati said: “A discovery we made studying the eye, about an expected property of anti-HIV drugs, has now led to a possible new way of thinking about MS.

“Going after the inflammasome, which may be what actually kills the nerve cells, and not only the immune cells upstream, potentially could be beneficial not just for MS but for many other neurodegenerative diseases. And that would be tremendously exciting.”

K-9 has already been tested in clinical trials for eye conditions including diabetic macular oedema and thyroid eye disease, providing safety data that could support trials in MS.

Ambati also co-founded Inflammasome Therapeutics in 2016 to study K-9 in amyotrophic lateral sclerosis.

The MS findings come from a mouse model. The researchers said the next step would be a clinical trial in people with MS.

Ambati said: “The next step in MS is a carefully designed clinical trial in people with MS, and NfL gives us an objective blood marker to see early whether the drug is doing what it did in animals.”