JAK/STAT Inhibition in CNS Kohlmeier-Degos Disease

Study Description:

This single patient protocol will provide off-label treatment with a JAK/STAT ( Janus kinases/ Signal transducer and Activator of Transcription proteins) inhibitor to a patient with Kohlmeier Degos disease (K-D) with neurologic involvement. We hypothesize that ruxolitinib, which targets type I IFN (Interferons ) and IFN-gamma signaling, will attenuate various neurological manifestations of K-D that are observed clinically, radiologically or in abnormal laboratory findings in our K-D patient. This will help reduce IFN signaling in a manner that may slow or halt the disease progression as measured by the endpoints established below.

Objectives:

Primary Objective:

To test the hypothesis that JAK/STAT inhibition by ruxolitinib will delay progression of neuroradiological manifestations of our one patient with neurological involvement of K-D disease.

Exploratory Objectives:

• Assess changes in immune cell proportion using single cell RNAseq (scRNA-seq) in biospecimens such as skin, cerebrospinal fluid (CSF) and blood after 13 weeks and up to 73 weeks of ruxolitinib treatment.
• Assess changes in plasma/serum cytokines levels and IFN scores as well as biomarker assays in CSF/ blood samples after 13 weeks and up to 73 weeks of ruxolitinib treatment..
• To test the hypothesis that ruxolitinib will stabilize or improve clinical neurologic exams in this patient.

Endpoints:

Primary Endpoint:

The primary endpoint is stability or regression of existing enhancing lesions or no development of new enhancing lesions in the brain and spine observed in MRI evaluation after 13 weeks and up to 73 weeks of ruloxitinib (10 mg BID) compared to pre-treatment MRI images.

Exploratory endpoints of this study are clinical and potential surrogate biomarker efficacy data, including:

• Changes in transcriptome/RNA expression determined by scRNA-seq in skin, CSF and peripheral blood mononuclear cells (PBMCs) between baseline measurements and after 13 weeks and up to 73 weeks of treatment.
• Attenuation of plasma/serum cytokine levels and IFN scores as well as biomarker assays in CSF and blood samples between the baseline visit and after 13 weeks and up to 73 weeks of treatment.
• Stability OR improvement of motor and/or sensory function on clinical neurologic exams between the baseline visit and after 13 weeks and up to 73 weeks of treatment.

• INCLUSION CRITERIA:

The study design was constructed to treat one participant with CNS Kohlmeier Degos Disease. Therefore, there are no specific inclusion criteria.

Exclusion criteria

• Active life-threatening infections
• Hemoglobin <7 g/dL
• Platelet counts < 50 K /mcL
• Neutropenia (ANC <0.5 x k/mcL)
• Lymphopenia (ALC <0.2 x k/mcL)
• LFTs (liver function test) > 3 x time upper limit
• eGFR/CreatCr < 30 mL/min