serine and Acroosteolysis, Giaccai Type studies

Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
serine : An alpha-amino acid that is alanine substituted at position 3 by a hydroxy group.

Research Excerpts

Excerpt	Relevance	Reference
"In a pilot study with 14 HSAN1 patients, L-serine supplementation similarly reduced dSL levels."	2.76	Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. ( Brown, RH; Eichler, FS; Frosch, MP; Garofalo, K; Hornemann, T; Lee, HJ; Penno, A; Schmidt, BP; von Eckardstein, A, 2011)
"Those patients diagnosed with both HSAN1 and MacTel showed the most significant decrease in circulating sphingomyelins."	1.91	Divergent amino acid and sphingolipid metabolism in patients with inherited neuro-retinal disease. ( Ansell, BRE; Bahlo, M; Bernstein, PS; Bonelli, R; Egan, C; Friedlander, M; Fruttiger, M; Gantner, ML; Green, CR; Handzlik, MK; Hart, B; McGregor, GH; Metallo, CM; Reilly, MM; Trombley, J; Tzaridis, S; Wallace, M, 2023)
"Two variants known to cause HSAN1 were identified as causal for macular telangiectasia type 2: of 11 patients with HSAN1, 9 also had macular telangiectasia type 2."	1.51	Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. ( Allikmets, R; Badur, MG; Bahlo, M; Baldini, M; Bernstein, PS; Bonelli, R; Cai, C; Dorrell, MI; Eade, K; Egan, C; Eichler, F; Fallon, R; Friedlander, M; Fruttiger, M; Gantner, ML; Giles, S; Gillies, M; Guymer, R; Handzlik, MK; Harkins-Perry, S; Hart, BJ; Heeren, TFC; Ideguchi, Y; Kitano, M; Metallo, CM; Nagasaki, T; Okada, M; Sauer, L; Scheppke, L; Trombley, J; Wallace, M; Woods, SM, 2019)
"In conclusion, we showed that HSAN1 mutations in SPT have distinct biochemical properties, which allowed for the prediction of the clinical symptoms on the basis of the plasma sphingoid base profile."	1.43	HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship. ( Alecu, I; Bode, H; Bourquin, F; Hornemann, T; Othman, A; Suriyanarayanan, S; Von Eckardstein, A; Wei, Y, 2016)

Research

Studies (18)

Authors

Clinical Trials (2)

Trial Overview

Trial Outcomes

1-deoxy-sphinganine

Timeframe	Studies, this research(%)	All Research%
pre-1990	1 (5.56)	18.7374
1990's	0 (0.00)	18.2507
2000's	2 (11.11)	29.6817
2010's	9 (50.00)	24.3611
2020's	6 (33.33)	2.80

Authors	Studies
Rodrigues, FG	1
Pipis, M	1
Heeren, TFC	2
Fruttiger, M	3
Gantner, M	1
Vermeirsch, S	1
Okada, M	2
Friedlander, M	3
Reilly, MM	3
Egan, C	3
Lone, MA	3
Aaltonen, MJ	1
Zidell, A	1
Pedro, HF	1
Morales Saute, JA	1
Mathew, S	1
Mohassel, P	2
Bönnemann, CG	2
Shoubridge, EA	1
Hornemann, T	8
Fiorillo, C	1
Capodivento, G	1
Geroldi, A	1
Tozza, S	1
Moroni, I	1
Cataldi, M	1
Campana, C	1
Morando, S	1
Panicucci, C	1
Pedemonte, M	1
Brolatti, N	1
Siliquini, S	1
Traverso, M	1
Baratto, S	1
Debellis, D	1
Magri, S	1
Prada, V	1
Bellone, E	1
Salpietro, V	1
Donkervoort, S	1
Gable, K	2
Gupta, SD	2
Dunn, TM	2
Taroni, F	1
Bruno, C	1
Schenone, A	1
Mandich, P	1
Nobbio, L	1
Nolano, M	1
Green, CR	1
Bonelli, R	2
Ansell, BRE	1
Tzaridis, S	1
Handzlik, MK	2
McGregor, GH	1
Hart, B	1
Trombley, J	2
Bernstein, PS	2
Wallace, M	2
Bahlo, M	2
Metallo, CM	2
Gantner, ML	2
Wilson, LMQ	1
Saba, S	1
Li, J	1
Prasov, L	1
Miller, JML	1
Eade, K	1
Fallon, R	1
Giles, S	1
Harkins-Perry, S	1
Sauer, L	1
Ideguchi, Y	1
Baldini, M	1
Scheppke, L	1
Dorrell, MI	1
Kitano, M	1
Hart, BJ	1
Cai, C	1
Nagasaki, T	1
Badur, MG	1
Woods, SM	1
Gillies, M	1
Guymer, R	1
Eichler, F	2
Allikmets, R	1
Clark, AJ	1
Kugathasan, U	1
Baskozos, G	1
Priestman, DA	1
Fugger, N	1
Othman, A	3
Chu, KH	1
Blesneac, I	1
Wilson, ER	1
Laurà, M	1
Kalmar, B	1
Greensmith, L	1
Platt, FM	1
Bennett, DL	1
Auranen, M	1
Toppila, J	1
Suriyanarayanan, S	3
Paetau, A	1
Tyynismaa, H	1
Ylikallio, E	1
Fridman, V	1
Novak, P	1
David, W	1
Macklin, EA	1
McKenna-Yasek, D	1
Walsh, K	1
Aziz-Bose, R	1
Oaklander, AL	1
Brown, R	1
Auer-Grumbach, M	1
Bode, H	2
Pieber, TR	1
Schabhüttl, M	1
Fischer, D	1
Seidl, R	1
Graf, E	1
Wieland, T	1
Schuh, R	1
Vacariu, G	1
Grill, F	1
Timmerman, V	2
Strom, TM	1
Bianchi, R	1
Alecu, I	2
Wei, Y	2
Porretta-Serapiglia, C	1
Lombardi, R	1
Chiorazzi, A	1
Meregalli, C	1
Oggioni, N	1
Cavaletti, G	1
Lauria, G	1
von Eckardstein, A	3
Bourquin, F	1
Han, G	1
Niranjanakumari, S	1
Harmon, JM	1
Scherer, SS	1
Garofalo, K	1
Penno, A	1
Schmidt, BP	1
Lee, HJ	1
Frosch, MP	1
Brown, RH	1
Eichler, FS	1
Verhoeven, K	1
Coen, K	1
De Vriendt, E	1
Jacobs, A	1
Van Gerwen, V	1
Smouts, I	1
Pou-Serradell, A	1
Martin, JJ	1
De Jonghe, P	1
Hirabayashi, Y	1
Furuya, S	1
Suzuki, T	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of L-Serine in Subjects With Hereditary Sensory Neuropathy Type 1[NCT01733407]	Phase 1/Phase 2	18 participants (Actual)	Interventional	2013-09-30	Completed
Tolerability and Efficacy of L-Serine in Patients With Amyotrophic Lateral Sclerosis: A Phase IIa Study[NCT03580616]	Phase 2	43 participants (Actual)	Interventional	2018-10-24	Terminated (stopped due to Study was terminated by the IRB due to continued noncompliance.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Plasma levels of the deoxysphingoid lipid 1-deoxy-sphinganine measured by liquid chromatography/mass spectrometry after hydrolyzing the N-acyl and O-linked headgroups (NCT01733407)
Timeframe: 48 Weeks

1-deoxy-sphingosine

Intervention	micromole per liter (Mean)
Sugar Pill	0.338
L-serine	0.112

Plasma levels of the deoxysphingoid lipid 1-deoxy-sphingosine measured by liquid chromatography/mass spectrometry after hydrolyzing the N-acyl and O-linked headgroups (NCT01733407)
Timeframe: 48 weeks

Autonomic Function Testing (AFT) Composite Autonomic Severity Score (CASS)

Intervention	micromole per liter (Mean)
Sugar Pill	0.698
L-serine	0.337

Autonomic Function Testing (AFT) tests the effectiveness of your autonomic nervous system which regulates important functions such as blood pressure, heart rate, and respiration. AFT results are quantified using the composite autonomic severity score scale (CASS) which is a scale from 0 to 10 that is the sum of three sub scores (cardiovagal, adrenergic, and sudomotor). Cardiovagal is scored from 0 to 3, sudomotor is scored from 0 to 3, and adrenergic is scored from 0 to 4. The tests include deep breathing, Valsalva maneuver, head-up tilt, and a sweat test. The three subscores are then summed. This total represents the CASS which classifies autonomic function as normal functioning (total score 0), mild (total score 1-3), moderate (total score 4-6), or severe (total score 7-10). (NCT01733407)
Timeframe: 48 Weeks

Charcot Marie Tooth Neuropathy Score

Intervention	scores on a scale (Mean)
Sugar Pill	3.56
L-serine	2.22

The Charcot Marie Tooth Neuropathy Score (CMTNS) is a 0 to 36 point composite scoring assessment that is used to measure disease severity in Charcot Marie Tooth Neuropathy and other sensory and motor neuropathies. The CMTNS is composed of 9 items that evaluate functions related to disease progression. These 9 parameters include reviewing sensory symptoms, motor symptoms (arms and legs), pinprick sensibility, vibration, leg strength, arm strength, and nerve conduction tests. Each item is scored from 0 to 4, with the lower scores representing less severe symptoms and higher scores representing more severe symptoms.The 9 individual item scores are then totaled to provide a global measure of disease severity. For example the lowest possible total score is 0 which represents an asymptomatic individual and the highest score possible is a 36 which represents an individual with severe disease progression. There are sub scores that can be assessed but sub scores were not utilized in this study (NCT01733407)
Timeframe: 48 Weeks

Intraepidermal Nerve Fiber Density (IENFD)

Intervention	scores on a scale (Mean)
Sugar Pill	25.67
L-serine	20.22

Counts of nerve fibers per unit area in skin biopsies (NCT01733407)
Timeframe: 48 Weeks

Nerve Conduction Testing

Intervention	nerve fibers per micrometer^2 (Mean)
	Upper Thigh	Lower Calf
L-serine	49.56	13.89
Sugar Pill	34.67	0.89

Evaluates the functioning of electrical conduction of the motor and sensory nerves of the human body. (NCT01733407)
Timeframe: 48 Weeks

Intervention	microvolts (Mean)
	Sensrory Right Median Amplitude	Sensory Right Antebrach Amplitude	Sensory Right Superficial Radial Amplitude	Sensory Right Sural Amplitude	Sensory Right Superficial Peroneal Amplitude	Motor Right Median (Wrist) Amplitude	Motor Right Ulnar (Wrist) Amplitude	Motor Right Peroneal EDB (Ankle) Amplitude	Motor Right Peroneal Tib (Below) Amplitude
L-serine	5.51	5.89	10.84	1.07	0.00	4.21	4.37	0.24	1.39
Sugar Pill	1.34	2.31	4.56	0.52	0.00	3.34	2.49	0.54	0.29

Article	Year
Roles of l-serine and sphingolipid synthesis in brain development and neuronal survival. Progress in lipid research, 2008, Volume: 47, Issue:3 Topics: Animals; Brain; Cell Survival; Disease Models, Animal; Enzyme Inhibitors; Hereditary Sensory and Aut	2008
[Management of autonomic disorders in amyloidosis]. Nihon rinsho. Japanese journal of clinical medicine, 1979, Sep-10, Volume: 37, Issue:9 Topics: Amyloidosis; Catecholamines; Droxidopa; Hereditary Sensory and Autonomic Neuropathies; Humans; Hypot	1979

Article	Year
Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1. Neurology, 2019, 01-22, Volume: 92, Issue:4 Topics: Adolescent; Adult; Aged; Double-Blind Method; Female; Follow-Up Studies; Hereditary Sensory and Auto	2019
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. The Journal of clinical investigation, 2011, Volume: 121, Issue:12 Topics: Administration, Oral; Adult; Aged; Alanine; Animals; Depression, Chemical; Dose-Response Relationshi	2011
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. The Journal of clinical investigation, 2011, Volume: 121, Issue:12 Topics: Administration, Oral; Adult; Aged; Alanine; Animals; Depression, Chemical; Dose-Response Relationshi	2011
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. The Journal of clinical investigation, 2011, Volume: 121, Issue:12 Topics: Administration, Oral; Adult; Aged; Alanine; Animals; Depression, Chemical; Dose-Response Relationshi	2011
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. The Journal of clinical investigation, 2011, Volume: 121, Issue:12 Topics: Administration, Oral; Adult; Aged; Alanine; Animals; Depression, Chemical; Dose-Response Relationshi	2011

Article	Year
Description of a patient cohort with Hereditary Sensory Neuropathy type 1 without retinal disease Macular Telangiectasia type 2 - implications for retinal screening in HSN1. Journal of the peripheral nervous system : JPNS, 2022, Volume: 27, Issue:3 Topics: Hereditary Sensory and Autonomic Neuropathies; Humans; Retinal Telangiectasis; Serine; Serine C-Palm	2022
SPTLC1 variants associated with ALS produce distinct sphingolipid signatures through impaired interaction with ORMDL proteins. The Journal of clinical investigation, 2022, 09-15, Volume: 132, Issue:18 Topics: Amyotrophic Lateral Sclerosis; Hereditary Sensory and Autonomic Neuropathies; Humans; Membrane Prote	2022
The SPTLC1 p.S331 mutation bridges sensory neuropathy and motor neuron disease and has implications for treatment. Neuropathology and applied neurobiology, 2022, Volume: 48, Issue:7 Topics: Hereditary Sensory and Autonomic Neuropathies; Humans; Motor Neuron Disease; Mutation; Peripheral Ne	2022
Divergent amino acid and sphingolipid metabolism in patients with inherited neuro-retinal disease. Molecular metabolism, 2023, Volume: 72 Topics: Alanine; Amino Acids; Animals; Glycine; Hereditary Sensory and Autonomic Neuropathies; Mice; Retinal	2023
Specific Deoxyceramide Species Correlate with Expression of Macular Telangiectasia Type 2 (MacTel2) in a SPTLC2 Carrier HSAN1 Family. Genes, 2023, 04-18, Volume: 14, Issue:4 Topics: Hereditary Sensory and Autonomic Neuropathies; Humans; Male; Serine; Serine C-Palmitoyltransferase;	2023
Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. The New England journal of medicine, 2019, 10-10, Volume: 381, Issue:15 Topics: Adult; Aged; Animals; Disease Models, Animal; DNA Mutational Analysis; Exome; Female; Hereditary Sen	2019
An iPSC model of hereditary sensory neuropathy-1 reveals L-serine-responsive deficits in neuronal ganglioside composition and axoglial interactions. Cell reports. Medicine, 2021, 07-20, Volume: 2, Issue:7 Topics: Aging; Axons; Base Sequence; Caspase 3; Cell Line; Gangliosides; Gene Expression Regulation; Heredit	2021
Clinical and metabolic consequences of L-serine supplementation in hereditary sensory and autonomic neuropathy type 1C. Cold Spring Harbor molecular case studies, 2017, Volume: 3, Issue:6 Topics: Adult; Dietary Supplements; Female; Hereditary Sensory and Autonomic Neuropathies; Humans; Mutation;	2017
Mutations at Ser331 in the HSN type I gene SPTLC1 are associated with a distinct syndromic phenotype. European journal of medical genetics, 2013, Volume: 56, Issue:5 Topics: Child, Preschool; Exons; Female; Hereditary Sensory and Autonomic Neuropathies; Humans; Mutation; Ph	2013
Lowering plasma 1-deoxysphingolipids improves neuropathy in diabetic rats. Diabetes, 2015, Volume: 64, Issue:3 Topics: Animals; Body Weight; Diabetic Neuropathies; Eating; Electrophysiology; Hereditary Sensory and Auton	2015
HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship. Human molecular genetics, 2016, Mar-01, Volume: 25, Issue:5 Topics: Adult; Aged; Alanine; Catalytic Domain; Child; Gas Chromatography-Mass Spectrometry; Gene Expression	2016
A disease-causing mutation in the active site of serine palmitoyltransferase causes catalytic promiscuity. The Journal of biological chemistry, 2010, Jul-23, Volume: 285, Issue:30 Topics: Alanine; Animals; Biocatalysis; Catalytic Domain; CHO Cells; Cricetinae; Cricetulus; Extracellular S	2010
The debut of a rational treatment for an inherited neuropathy? The Journal of clinical investigation, 2011, Volume: 121, Issue:12 Topics: Animals; Female; Hereditary Sensory and Autonomic Neuropathies; Humans; Lipids; Male; Neurotoxins; S	2011
SPTLC1 mutation in twin sisters with hereditary sensory neuropathy type I. Neurology, 2004, Mar-23, Volume: 62, Issue:6 Topics: Acyl Coenzyme A; Acyltransferases; Belgium; Chromosome Mapping; Chromosomes, Human, Pair 9; Disease	2004

serine and Acroosteolysis, Giaccai Type