Editing Serine


==Serine in ALS==

Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase (14.52 cM region on chromosome 12q22-23 linked to disease). D-amino acid oxidase gene (R199W DAO) controls the level of D-serine, which accumulates in the spinal cord in cases of sporadic ALS and in a mouse model of ALS, indicating that this abnormality may represent a fundamental component of ALS pathogenesis.{{#pmid:20368421|mitchell2010}}

To better understand the distribution of d-serine in ALS, researchers determined the activity and the expression of serine transporter in a motor neuronal cell line model of ALS (NSC-34/hSOD1G93A cells). Data suggest that the pathological alteration of d- and l-serine uptakes in ALS is driven by the affinity change of d-and l-serine uptake system.{{#pmid:28043791|lee2017}}

"'''The ALSFRS-R in the l-serine-treated patients showed a dose-related decrease in the rate of progression (34% reduction in slope, P = 0.044)'''. The non-random distribution of addresses of ALS patients suggests that '''residential exposure to environmental pollutants may play an important role in the etiology of ALS'''. '''l-Serine in doses up to 15 g twice daily appears to be safe in patients with ALS. Exploratory studies of efficacy suggested that l-serine might slow disease progression'''. A phase II trial is planned." [https://link.springer.com/article/10.1007/s12640-017-9741-x Source]

==ALSUntangled conclusion==

"L-serine is a reasonably inexpensive, widely available nutritional  supplement  that  has  a  plausible  mechanism  by  which  it  could  help  a  subset  of  patients who might have ALS from BMAA-toxicity. A small Phase I trial showed that L-serine up to 15 g twice daily is relatively well tolerated. A larger follow up trial  is  planned  and  will  shed  further  light  on  its safety and utility as an ALS therapeutic.
Unfortunately,  since  it  is  challenging  to  reliably measure  BMAA  in  PALS,  it  will  be  difficult  to identify  the  subset  most  likely  to  respond.  Until  a reliable  assay  for  measuring  BMAA  exposure  in living  people  arises,  or  a  follow  up  trial  confirms safety and demonstrates benefit independent of this, we  cannot  recommend  L-serine  as  a  treatment for ALS."

NOTE: ALSUntangled conclusion was written before this article [https://link.springer.com/article/10.1007/s12640-017-9741-x (Studies of Environmental Risk Factors in Amyotrophic Lateral Sclerosis (ALS) and a Phase I Clinical Trial of l-Serine)] was published.

==References==

[[Category:Supplement data pages]]