JAK/STAT Inhibition in CNS Kohlmeier-Degos Disease

Overview

Background: Kohlmeier-Degos (K-D) is a rare disease that leads to the inflammation and/or blockage of small blood vessels in many organs; these can include the skin, eyes (rare), small bowels, lungs, heart, and the brain and spinal cord (central nervous system, or CNS). There are no known effective treatments for K-D that affects the CNS. Objective: To test a drug (ruxolitinib) in a person with K-D affecting the CNS. Eligibility: This study is designed to treat 1 adult participant with K-D affecting the CNS. Design: The participant will be screened: They will have a physical exam and blood tests. They will have skin biopsies: Small samples of skin will be removed. They will have a lumbar puncture: A needle will be inserted in his back to draw fluid from the space around the spinal cord. They will have a magnetic resonance imaging (MRI) scan: they will lie on a table that slides into a tube to take pictures of their brain and spinal cord. They will see a doctor who specializes in nerves. Ruxolitinib is a tablet taken by mouth. The participant will take the drug twice a day for up to 26 weeks. The dosage may change over time. The participant will have up to 7 clinic visits in 28 weeks. Each visit will be 1 to 3 days. MRI scans, biopsies, lumbar punctures, and other blood tests will be repeated on different visits. The participant may receive follow-up phone calls between visits. The participant will report any adverse effects. Unscheduled visits may be needed if new symptoms develop. The last follow-up will be 4 weeks after the last dose of the study drug.

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: 1. 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. 2. 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.. 3. 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: 1. 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. 2. 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. 3. 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.