High levels of bone morphogenetic protein-9 (BMP-9) in the serum are associated with better outcomes in patients with neuromyelitis optica spectrum disorder (NMOSD) who are seropositive for aquaporin-4 antibody (AQP4), according to a new study published in the journal Scientific Reports.

The study also reported that BMP-9 was upregulated during an NMOSD attack and could contribute to vascular remodeling.

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Previous research has shown that patients with AQP4-positive  NMOSD (AQP4+NMOSD) have worse outcomes compared to those with antimyelin oligodendrocyte glycoprotein-associated disorders (MOGAD), the researchers noted.

It is also known that recurrent neuroinflammation leads to lymphatic vessel remodeling in the central nervous system, they added.

To better understand which cytokines in the serum are most important to this remodeling after an NMOSD attack in patients with AQP4 + NMOSD, a team of researchers led by Satoshi Kuwabara, MD, PhD, from Chiba University, in Chiba-Shi, Japan, measured the levels of 12 cytokines that are relevant to vascular remodeling, including BMP-9 and leptin in the serum of 20 patients with AQP4+NMOSD, 18 patients with MOGAD, and 17 healthy volunteers.

The researchers also measured the levels of interleukin-6 in the blood and cerebrospinal fluid of the participants and assessed the clinical severity of the disease using the Expanded Disability Status Scale.

The results showed that the levels of BMP-9 and leptin were higher in patients with AQP4+NMOSD compared to healthy people but not in patients with MOGAD. 

When the levels of BMP-9 were higher in the serum, the improvement in EDSS scores at 6 months was better, the researchers also reported. 

“BMP-9 is upregulated at relapse and may contribute to vascular remodeling in AQP4 + NMOSD,” they concluded. “Serum BMP-9 levels could predict clinical recovery 6 months after the attack.” 


Masuda H, Mori M, Uzawa A, et al. Elevated serum levels of bone morphogenetic protein-9 are associated with better outcomes in AQP4-IgG seropositive NMOSD. Sci Rep. Published online March 2, 2023. doi:10.1038/s41598-023-30594-z