Drug May Slow Secondary Progressive Multiple Sclerosis

Fingolomid appears to reduce the harmful activities of astrocytes in MS.

A new study testing an already-approved multiple sclerosis drug is giving researchers new hope that they may soon be able to slow the progression of secondary progressive multiple sclerosis (SPMS).

Researchers at Brigham and Women’s Hospital (BWH) showed that FTY720 (fingolimod) can reduce the pathogenic activities of astrocytes, which are thought to play a central role in the progression of SPMS.

“One of the most important unmet clinical needs in MS is to design therapeutic approaches for the progressive phase of the disease,” said Francisco Quintana, PhD, a researcher in the Ann Romney Center for Neurologic Diseases at BWH, in a press release. “And a key unanswered question related to that is, what are the biological processes that drive disease pathogenesis at this stage?”

SPMS is associated with severe disability in young adults, causing neurological deficits that to date are irreversible.

Fingolimod, which is sold by Novartis under the trade name Gilenya, was approved in 2010 for the treatment of relapsing-remitting multiple sclerosis (RRMS). At the time of its approval, the Food and Drug Administration noted that the drug worked by blocking some blood cells in the lymph nodes, thereby reducing their migration to the brain and spinal cord and potentially reducing the severity of MS.

In the BWH study, scientists decided to look specifically at whether the drug could inhibit astrocytes. The goal was to curb astrocyte activation by modulating the lipid Sphingosine-1-receptor (S1PR) using fingolimod. The results were positive. Researchers found fingolimod improved chronic progressive experimental autoimmune encephalomyelitis (EAE) in nonobese diabetic mice. Chronic progressive EAE shares many similarities with SPMS.

Furthermore, in both human and mice in vitro assays, S1PR decreased astrocytes’ pro-inflammatory and neurotoxic properties, and also appeared to help cells fight off inflammation.

Additionally, “[g]enome-wide studies showed that FTY720 suppresses transcriptional programs associated with the promotion of disease progression by astrocytes,” the authors wrote.

The new research suggests that scientists may be zeroing in on an effective approach to SPMS drug development. However, the researchers say there are still a number of questions to be answered. They also cautioned that the neuroprotective traits of fingolimod are not as strong as those recorded in studies of other therapies.

Meanwhile, Quintana noted that Novartis is already carrying out an SPMS trial of a similar drug to fingolimod. Novartis’ EXPAND study is looking at BAF312 (siponimod) as a treatment for SPMS. Siponimod is a modified and more targeted version of fingolimod.

Novartis presented preliminary Phase III findings from the EXPAND study in September at the European Committee for Treatment and Research of Multiple Sclerosis (ECTRIMS) meeting in London. They showed a 21% reduction in three-month confirmed disability progression versus placebo.

Novartis contributed funding to the BWH study.

About 400,000 people in the US and 2.3 million people worldwide have multiple sclerosis. It’s estimated that at least 50% of the people with relapsing-remitting MS will progress to SPMS.

The BWH study, “Sphingosine 1-phosphate receptor modulation suppresses pathogenic astrocyte activation and chronic progressive CNS inflammation,” was published February 6 in PNAS.

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