Therapeutic Effect of Recombinant Human Growth Hormone (rhGH) on the Myopathy of Cystinosis

Cystinosis is an autosomal recessive storage disorder due to defective transport of the
amino acid cystine out of cellular lysosomes. Cystine accumulation leads to cellular
dysfunction in most of organs and tissues. Available treatment with the cystine-depleting
agent, cysteamine, can prevent or delay organ damage, including that of muscles. In poorly
treated patients, however, a progressive vacuolar myopathy with muscle wasting beginning in
the second decade of life significantly debilitates some patients. Muscle biopsy
demonstrates prominent unrimmed vacuoles with small ring fibers but no evidence of
endomysial inflammation. Plasma and muscle carnitine deficiency, impairing mitochondrial
fatty acid metabolism, might also limit muscle energy production. Growth Hormone (GH) can
potentially counter the muscle wasting of cystinosis patients. It has consistently induced
anabolic effects in patients in malnourished or catabolic states, by enhancing the growth
and development of bone, connective tissue, viscera, fat, and musculoskeletal muscles. GH,
at doses of approximately 0.006 to 0.1 mg/kg/day, has proven safe and effective in HIV/AIDS
wasting, parenteral nutrition-dependent short bowel syndrome, pediatric chronic kidney
disease, and adult and pediatric GH-deficiency states. The current protocol is a randomized
(to treatment or no treatment) crossover clinical trial to determine if GH (0.03 mg/kg/day)
is beneficial for muscle wasting in cystinosis. Patients are examined at the NIH Clinical
Research Center every 4 months for 2 years. Change in muscle mass will serve as the primary
outcome parameter, and rhGH (Humatrope) will be provided by Eli Lilly. HumatropeR
(somatropin) is currently approved by the FDA for:

- Treatment of children with short stature or growth failure associated with growth
hormone (GH) deficiency, Turner syndrome, idiopathic short stature, SHOX deficiency,
and failure to catch up in height after small for gestational age birth.

- Treatment of adults with either childhood-onset or adult-onset GH deficiency.

- INCLUSION CRITERIA:

- Age 18-70 years, either gender

- Diagnosis of nephropathic cystinosis confirmed by leucocyte cystine levels

- Evidence of muscle involvement such as decrease of muscle mass, weakness or EMG
findings and/or documented abnormal swallowing study and PFT results

- Ability to travel to the NIH Clinical Research Center for admissions

- Ability to consent

- Compliant with cysteamine treatment regimen

- Availability of local medical follow-up

ENCLUSION CRITERIA:

- Not able to self administer daily subcutaneous injections, or not able to identify a
family member/caregiver to administer them to you.

- Age < 18

- Psychiatric illness or neurological disease that interferes with compliance or
communication with health care personnel

- Current malignancy or history of malignancy

- Uncontrolled hypertension (blood pressure > 180 systolic or > 95 diastolic)

- Poor controlled hyperglycemia (fasting blood glucose level > 160)

- Serum creatinine level > 1.8 mg/dL

- Pregnancy

Children are excluded because the critical issues of dosage and safety can be answered in
adults, and because children with cystinosis are rarely affected with the symptoms of
myopathy. Patients with chronic renal failure, treated with hemodialysis will not be
excluded from the study, as GH is not contraindicated for such patients. Patients received
renal transplants are not excluded from the study as GH treatment are not a
contraindication for such patients. Enrolled patients must be able to travel to the NIH in
case adverse events occur locally after discharge from the NIH Clinical Research Center.
Other medical exclusions will help to avoid the spurious assignation of side effects to
rhGH.