The long-term goal of the research in my lab is the repair of damaged corticospinal circuitry. Attempts at therapeutic regeneration are limited both by the current understanding of the mechanisms that underlie the sequential generation and development of corticospinal motor neurons (CSMN) and by the current understanding of the events occurring within CSMN in the setting of spinal cord injury. A thorough understanding of the molecular controls over CSMN development might enable enhancement of corticospinal regeneration. MicroRNAs are small, non-coding RNAs that have recently been identified to regulate the expression of pathways of genes in development and disease. MicroRNAs repress their taraget genes at the messenger RNA (mRNA) level, either by degrading the mRNA or by repressing its translation. The work in my lab seeks to identify microRNA controls over the CSMN development and over CSMN response to spinal cord injury.
Major research focus areas of the laboratory
microRNA CONTROLS OVER CORTICOSPINAL MOTOR NEURON DEVELOPMENT: We have identified a group of microRNAs that are differentially expressed in CSMN compared to the highly related callosal projection neurons (CPN) during development. We are testing the ability of these microRNAs to control CSMN fate. We are also working to identify their messenger RNA targets relevant to CSMN and CPN development.
microRNA CONTROLS OVER CSMN RESPONSE TO SPINAL CORD INJURY: This work investigates microRNAs acting in CSMN in the setting of spinal cord injury. In addition, building upon our developmental work, we are investigating the potential roles of developmentally regulated microRNAs in CSMN regenerative strategies to treat spinal cord injury, including stem cell-based strategies.
MR Guided High Intensity Focused Ultrasound for Lumbar Back Pain
The primary purpose of this protocol is to assess the ExAblate 2100 MR guided high intensity focused ultrasound device as an intervention for treatment of facetogenic lower back pain
This study is currently recruiting participants.
This is a single group, single arm, open/nonblinded, non-randomized study. The primary outcomes are safety and preliminary efficacy. The InSightec ExAblate 2100 MRgHIFU system is a non-invasive thermal ablation device fully integrated with an MR imaging system and used for the ablation of soft tissue and bone.The study will reach primary completion 12 months from the time the study opens to accrual.
Men and women > 21 years of age and who are skeletally mature
Body mass index ≤ 30 kg/m2
Patients who are able to understand and willing to sign a written informed consent document and able to attend all study visits
Patients with at least 6 months of chronic lower back pain (LBP) localized to the midline or axial low back, with symptoms attributed to the facet joints on physical examination that have persisted despite conservative therapy. Conservative therapy is defined as systemic pain medications and anti-inflammatory medications, as well as physical therapy, such as massage, heating, hydrotherapy, and strengthening exercises.
Patients with Numerical Rating Scale worst lumbar back pain score of at least 4 out of 10 over the 24 hours preceding the time of rating.
Patients must have chronic LBP attributed to facet joints as demonstrated by MRI consistent with at least grade 2 facet joint arthritis, with corresponding abnormal activity at the facet joint on 18F-sodium fluoride PET-CT.
Patients must have an analgesic response to either prior local anesthetic injection to the facet joint or to radiofrequency ablation of the facet joint, with relapse of pain.
The targeted facet joint must be deeper than 10 mm from the skin
Patients with severe lumbar lordosis
Patients with contraindication for MR imaging such as implanted metallic devices that are not MRI-safe, size limitations, claustrophobia. etc
Patients with known intolerance or allergy to MR contrast agent (gadolinium chelates) including advanced kidney disease (GFR <30 mL/min/1.73 m2) or on dialysis
Pregnant and nursing patients will be excluded from the study because of a contraindication to administering MRI contrast agents to these patients
Patients with known intolerance or allergy to medications used for sedation (midazolam), analgesia (fentanyl), and local and regional anesthesia (lidocaine, bupivacaine, and ropivacaine)
Patients with evidence of lumbosacral radiculopathy on MRI or physical exam findings, including radicular leg pain, or any neurologic deficit at or below the segmental level of the highest facet to be treated, including subjects with impaired sphincter control
Patients with pain at another location that
cannot be distinguished from lumbar back pain
does not rate at least 2 points less in worst pain score compared to lumbar back pain
requires the use of analgesics
Patients with gross spinal instability on imaging
Patients who have lumbar spinal stabilization hardware in place
NOT visible by non-contrast MRI, OR
NOT accessible to ExAblate device
Individuals who are not able or willing to tolerate the required prolonged stationary position during treatment (can be up to 5 hrs of total table time)
Patients with acute medical condition (e.g. pneumonia, sepsis) that is expected to hinder them from completing this study
Patients with unstable cardiac status including:
Unstable angina pectoris on medication
Patients with documented myocardial infarction within six months of protocol entry
Congestive heart failure requiring medication (other than diuretic)
Patients on anti-arrhythmic drugs
Patients with severe hypertension (diastolic BP > 100 on medication)
Patients with severe hematologic, neurologic, or other uncontrolled disease (e.g. platelets < 50,000/microL, INR > 1.5)
Patients who are taking anti-thrombotic medication
Severe cerebrovascular disease (multiple CVAs or CVA within 6 months)
Patients with inflammatory arthritides.
Patients unable to communicate with the investigator and staff
Patients seeking compensation for disability or work injury.
Patients who are part of another trial testing other Investigational Agent
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02291978