Stem Cell Transplantation for Stiff Person Syndrome (SPS) (SPS)
Stiff-Person Syndrome
About this trial
This is an interventional treatment trial for Stiff-Person Syndrome focused on measuring Autoimmune Diseases, Autologous Hematopoietic Stem Cell Transplantation
Eligibility Criteria
Inclusion Criteria:
Diagnosis of Stiff-person Syndrome and
- Age between 18 and 60 years old
- Failure of medically tolerable doses (20-40 mg/day) of diazepam
- Failure of either intravenous immunoglobulin (IVIg) and or plasmapheresis
- Stiffness in the axial muscles, prominently in the abdominal and thoracolumbar paraspinal muscle leading to a fixed deformity (hyperlordosis)
- Superimposed painful spasms precipitated by unexpected noises, emotional stress, tactile stimuli
- Confirmation of the continuous motor unit activity in agonist and antagonist muscles by electromyography when off diazepam and anti-spasmatic medications
- Absence of neurological or cognitive impairments that could explain the stiffness
- Inability to run or walk, or abnormal gait
Diagnosis of a SPS variant- Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) defined as:
Acute onset of painful rigidity and muscle spasms in the limbs and trunk
- Brainstem dysfunction (nystagmus, opsoclonus, ophthalmoparesis, deafness, dysarthria, dysphagia)
- Profound autonomic disturbance.
- Positive serology for GAD65 (or amphiphysin) autoantibodies, assessed by immunocytochemistry, western blot or radioimmunoassay (>1000 u/ml)
- MRI may show increased signal intensity throughout the spinal cord and the brainstem
Diagnosis of a SPS variant - anti-GAD positive cerebellar ataxia
- Subacute or chronic onset of cerebellar symptoms-gait or limb ataxia, dysarthria, nystagmus
- Positive serology for GAD65 (or amphiphysin) autoantibodies, assessed by immunocytochemistry, western blot or radioimmunoassay (>1000 u/ml)
- Anti-GAD antibody in cerebrospinal fluid
- Abnormal MRI imaging of brainstem or cerebellum other than cerebellar atrophy
- Negative history of toxin or alcohol
- Absence of Vitamin B12 or Vitamin E deficiency
- Absence of positive HIV, syphilis or whipple disease
- Absence of consanguinity, positive family history for ataxia or positive genetic screen for spinocerebellar ataxia (SCA) 1, SCA 2, SCA 3, SCA 6, SCA 7 or SCA 8 mutation
Exclusion Criteria:
- Current or prior history of a malignancy or paraneoplastic syndrome
- Inability to sign and understand consent and be compliant with treatment
- Positive pregnancy test
- Inability to or comprehend irreversible sterility as a possible side effect
- Amphiphysin antibody positive
- Left ventricular ejection fraction (LVEF) < 45% or ischemic coronary artery disease on dobutamine stress echocardiogram
- Diffusing capacity of the lungs for carbon monoxide (DLCO) < 60% predicted
- Serum creatinine > 2.0 mg/dl
- Bilirubin >2.0 mg/dl
- Platelet count < 100,000 / ul, white blood cell count (WBC) < 1,500 cells/mm3
- History of toxin or alcohol abuse
- History of Vitamin B12 or Vitamin E deficiency
- Positive HIV, syphilis, or whipple disease
- Consanguinity, positive family history for ataxia or positive genetic screen for SCA1, SCA2, SCA3, SCA6, SCA 7 or SCA8 mutation (if ataxia present)
- Absence of at least one SPS associated antibody such as anti-GAD, or gamma-aminobutyric acid (GABA)-A receptor associated protein, or synaptophysin, or gephyrin, or GABA-transaminase
Sites / Locations
- Northwestern University
Arms of the Study
Arm 1
Experimental
Hematopoietic Stem Cell Transplantation
The conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with intravenous mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5, 1.0 mg/kg on days -4 and -3, and then 1.5 mg/kg on days -2 and -1. Methylprednisolone 1000 mg will be infused intravenously before each dose of rATG. Autologous hematopoietic stem cells will be infused intravenously on day 0. A granulocyte-colony stimulating factor (G-CSF) 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment. Intravenous Rituxan (500mg) will be administered on days -6 and +1.