A Pilot Study of Biomarkers for Spinal Muscular Atrophy

The goal of this pilot study is to identify a marker or panel of markers in the blood or urine from a wide range of Spinal Muscular Atrophy (SMA) patients that segregates with measures of clinical severity. From this identification of candidate biomarkers, it is hoped that further investigations, both longitudinal natural history and clinical efficacy studies, will verify a biomarker with the sensitivity and specificity that will allow its eventual use as a validated pharmacodynamic marker or surrogate endpoint. In addition, this effort may elucidate biological pathways that may be potential therapeutic targets.

Spinal Muscular Atrophy (SMA) is one of the two most common inherited children's neuromuscular disorders. There currently is no cure and no therapeutics approved to slow progression of the disease. SMA is characterized by a loss of alpha motor neurons in the spinal cord, severe atrophy of proximal muscles and progressive debility and disability due to respiratory, gastrointestinal and functional complications of the disease.

Although SMA is a relatively common orphan disease, recruitment of patients for the number of candidate therapies is expected to become rate-limiting for the development of therapeutics.

STUDY OBJECTIVES

Primary:

* To identify candidate blood and urine biochemical markers that correlate with disease severity as determined by the Modified Hammersmith Functional Motor Scale across a range of type I, type II and type III children with Spinal Muscular Atrophy (SMA) (1).

Secondary:

* To determine if there are biomarkers from types I-III SMA patients that correlate with SMA type, age at disease onset, 10-meter Timed Walk Test (ambulatory subjects only), pulmonary function, nutritional assessment, SMN protein level, SMN transcript level or SMN2 copy number.
* To determine if identified candidate biomarkers are associated with the disease state through comparison of SMA specimens with control volunteer specimens.
* To determine if there are potential biochemical pathways that may represent targets for therapeutic intervention in SMA.

Eligibility Criteria:
Inclusion Criteria:

* Age 2 to 12 years, inclusive
* In good health (other than SMA) in the judgement of the clinical investigator ar the time of assessment

Exclusion Criteria:

* Systemic or specific-organ illness
* Any known genetic condition other than SMA requiring pharmaceutical treatment
* Use of any putative SMN-enhancing medications or treatments in the past 14 days prior to enrollment
* Use of carnitine, creatine, oral albuterol or riluzole for 14 days prior to enrollment
* Use of any oral prescription medications for 14 days prior to enrollment (exceptions: anti-reflux medications, constipation or stoll softening medications, stool bulking agents, and inhaled bronchodilator medications)
* Any illness requiring treatment of antibiotics or anti-inflammatory medication within the past 14 days
* Any rash requiring treatment within the past 7 days
* Any severe asthma attack requiring treatment with oral or parenteral steroids within the past 7 days
* Any fever over 100 degrees Fahrenheit or 38 degree Celsius within the past 7 days
* Any immunization within the past 7 days
* Any injury sustained that resulted in a bone fracture or needed stitches within the past 7 days
* Any surgery within the past 7 days
* Any receipt of anesthesia within the past 7 days
* Any Emergency Room visit or hospitalization within the past 7 days
* Any stomach illness with vomiting within the past 7 days
* Any migraine headache within the past 7 days
* Participation in a clinical trial (except observational studies) within the past 7 days