M2 PHARMA-October 25, 2017-Aldeyra Therapeutics Data Show ADX-102 Reduces GHB and GABA in Mouse Model of SSADH Deficiency
(NASDAQ: ALDX) presented novel data at the American Society of Human Genetics 2017 annual meeting demonstrating that ADX-102 reduced levels of gamma-hydroxybutyrate (GHB) and gamma-aminobutyrate (GABA) in a knockout mouse model of Succinic Semialdehyde Dehydrogenase (SSADH) deficiency, the company said.
elata, appeared to irreversibly inactivate the succinic semialdehyde dehydrogenase (SSADH) of bovine brain in in vitro conditions (Table 3, entry 2; Fig.
Furthermore, structure-activity relationship analysis on 4-hydroxybenzaldehyde derivatives as GABA-T and SSADH inhibitors indicated that a carbonyl or an amino group as well as a hydroxyl group at the para-position of the benzene rings are important for the inhibition of both enzymes.
In the gastrodin-treated group, both succinic semialdehyde dehydrogenase (SSADH
) and succinic semialdehyde reductase (SSAR) immunoreactivities in the hippocampus was also decreased significantly, which stood in contrast to the nontreated group, in which strong SSADH
and SSAR immunoreactivities were detected.
Carolyn and Brad Hoffman (parents of Sam who has SSADH
) and Nancy Speller (mother of JJ, who, before he died, touched the hearts of everyone at EP) realized that no one was going to rally behind rare diseases that required two days of practice before you could pronounce the first three words of these complex conditions.
That GHB is an endogenous compound has been made even more evident by the recent description of an apparent inborn error of GHB metabolism due to a deficiency in succinic semialdehyde dehydrogenase (SSADH
[gamma]-Aminobutyric acid (GABA), the major inhibitory neurotransmitter, is metabolized by the successive action of GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH).
GABA is metabolized by the successive action of GABA transaminase (GABA-T), a pyridoxal 5'-phosphate-dependent enzyme, and succinic semialdehyde dehydrogenase (SSADH), a [NAD.sup.+]-dependent enzyme, to succinic acid, which is a substrate for the tricarboxylic acid cycle (Tao et al., 2006).
The diseases identified to date include: tyrosine hydroxylase deficiency (TH deficiency); aromatic L-amino acid decarboxylase deficiency (ALADD or AADC); GTP-1 cyclohydrolase deficiency (dopa-responsive dystonia); dihydropteridine reductase deficiency (DHPR); and succinic semialdehyde dehydrogenase deficiency (SSADH
These diseases include: GTP Cyclohydrolase I Deficiency (dopa responsive dystonia) and Tyrosine Hydroxylase Deficiency (both currently treatable), Aromatic L Amino Acid Decarboxylase Deficiency, and Succinic Semialdehyde Dehydrogenase (SSADH