Cerebral cavernous malformation (CCM) is a common vascular abnormality of the brain, affecting 0.1%-0.5% of people. It often causes recurrent brain hemorrhages, epilepsy, and neurological impairments, with surgery being the main treatment. However, surgery carries high risks for patients with multiple lesions or lesions in critical areas, and no effective pharmacological treatment is available. CCM is linked to mutations in genes like CCM1, CCM2, CCM3, or MAP3K3, which activate the MEK5-ERK5-KLF2/4 pathway, disrupting endothelial function. Immune cell infiltration, particularly plasma cells with high CD38 expression, suggests a role for humoral immunity in CCM. Depleting B cells in mouse models reduced lesions and hemorrhages, but broad B cell depletion is risky.
To find a safer treatment, researchers tested anti-CD38 monoclonal antibodies in mice, showing that targeting CD38 reduced CCM lesion formation. Given the success of CD38-targeted therapies like daratumumab in treating multiple myeloma, this study proposes evaluating daratumumab for CCM in a single-center trial with 10 adult patients to assess its safety and efficacy.
Age ≥ 18 years;
Diagnosed with familial cerebral cavernous malformation (familial CCM) (diagnosis requires at least one of the following: multiple CCMs or ≥2 family members with CCM);
Presence of clinical symptoms or history of symptomatic events: intracerebral hemorrhage, stroke, permanent or transient neurological deficits, seizures, disability, or any other neurological symptoms associated with cavernous malformations;
Deemed unsuitable for surgical resection by a physician;
Stable familial CCM lesions not requiring intervention;
Presence of metal implants or other contraindications to MRI;
History of statin therapy within the past 6 months;
History of beta-blocker therapy within the past 6 months;