Does arginine enhance galactose oxidative capacity in classic galactosemia? A pilot study

Classic galactosemia is a rare inherited metabolic disease that presents in
neonatal patients with a life-threatening multi-organ toxic syndrome. Although
a galactose-restricted diet quickly relieves the initial severe illness, it
fails to prevent long-term complications. Therefore, new therapies are required
to improve patient outcome.
Misfolding is a common molecular basis for GALT deficiency in classic
galactosemia, leading to protein aggregation. Chemical chaperones as arginine
can provide protein stability, thus preventing aggregation and enhancing its
residual activity. In a galactosemia bacterial model, arginine has shown to
stabilize GALT variant proteins. Accordingly, this might be a promising
therapeutic approach for classic galactosemia. As arginine is a well-known
amino acid that is therapeutically widely used and has showed no side effects
in previous studies, we propose to use it in a pilot study. We aim to evaluate
the effects of arginine administration in a classic galactosemia patient in
order to determine its possible role in the treatment of this disease.
Human fibroblasts will be cultured to gain further insights on galactose
metabolism upon arginine exposure and its mechanism of action.

The objective of this study is to evaluate the possible effect of arginine on
galactose oxidative capacity in 5 patients with classic galactosemia
(homozygous for the p.Q188R mutation).

Intervention study with pre-post design, single arm

All participants will receive arginine in the form of arginine aspartate
(Asparten ®) during 30 ± 5 days, by oral administration (3x/day).

The immediate benefit of participation is that general knowledge of classic
galactosemia will be extended. If a positive effect of arginine is found, the
benefit for the next generation galactosemia patients might be very large,
since this could be a first step in the development of a new therapeutic
strategy in classic galactosemia. If a new therapy could prevent long-term
complication, this would have a large effect on patient's quality of life.
However, there is no direct benefit for the participants; no relief of symptoms
is expected. Inevitably, side effects might occur, but this chance is estimated
to be very small. Participation brings the burden of taking medication 3 times
a day during 30 ± 5 days and 2 visits to the clinic where a venapunction and a
galactose oxidative capacity will be accomplished. A skin bipsy will be
performed once, at the outpatient clinic that patients normally visit. This
will limit the burden of participation. Overall we think the potential benefit
for the classic galactosemia community outweighs the limited risks and the
small burden of the study.