Behavioral Manifestations of Lesch-Nyhan Disease Clinical Trial
Official title:
Trial of Kuvan™ (Sapropterin) Treatment in Patients With Lesch Nyhan Disease
To assess the possibility that treatment with Kuvan (a form of tetrahydrobiopterin) will lessen the abnormal behavior and/or neurology commonly found in Lesch-Nyhan disease (LND); to assess biochemical changes as measured in blood and urine.
Lesch-Nyhan disease (LND) is an X-linked disorder of purine metabolism which results from
mutation in the gene for the enzyme hypoxanthineguanine phosphoribosyltransferase (HPRT);
patients have hyperuricemia, gout, urinary tract calculi, and nephropathy which are
effectively treated with allopurinol. There is also a syndrome of dystonia, chorea and
athetosis, as well as involuntary self mutilative biting and aggression toward their
caretakers, for which there is no treatment.
Kuvan™ is a form of tetrahydrobiopterin (BH4), and is approved to help lower the blood levels
of phenylalanine in people who have phenylketonuria (PKU). LND patients have been found to
have decreased BH4 in the spinal fluid and brain; BH4 is a precursor of dopamine, which has
an effect on behavior. In an earlier study Dr Nyhan found that treatment of LND with
5-hydroxytryptophan and carbidopa abolished the self-injurious behavior but was uniformly
transient.
This is a single site open-label protocol for eight subjects age 4 years and older with
Lesch-Nyhan Disease documented by deficiency of HPRT.
The study involves three study visits to San Diego and one study visit done locally. The
first visit will last 13 days, the following visits are single day visits at week 4 and week
8, and the local study visit is a brief outpatient visit at week 6. Physical and neurological
exams, videotaping of the patient's interactions with the study staff, and blood and urine
collection for laboratory analyses will be performed at each San Diego visit. A family member
or caregiver will be asked to complete a short assessment form and report any illness or
medication changes. In addition, the study staff will have weekly telephone contact with the
family to discuss any behavioral changes or study drug issues.
If the patient's self injurious behavior becomes worse after starting Kuvan the drug will be
discontinued and the patient will be followed until the behavior returns to baseline.
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