Milestones

2022 - Sarah Elsea, Ph.D., FACMG Professor, Dept. of Molecular and Human Genetics and Senior Director Biochemical Genetics at Baylor College of Medicine published her work documenting the genomic variants for SSADH and concluded that there are currently 98 reported variants, which indicates 1:460,000.

2022 – The biorepository was moved from Washington State University, to Boston Children’s Hospital.

2022 – The fourth year of the SSADH Natural History Study was concluded using a traveling phlebotomist to collect samples from patients within their own home. 

2022 – Held a Hybrid (in-person & virtual) Externally-Led Patient Focused Drug Development (EL-PFDD) meeting attended by over a hundred patients, caregivers and doctors gathered from across the US, and from as far away as Asia, Europe and Greece.  Additionally 13 members from the FDA attended.

2022 – Established and distributed a SSADH survey of symptoms, side effects, and the impact of SSADH on the patient and caregiver population.  The survey was distributed to patients, caregivers, family members, teachers and medical professionals.

2022 – Completed ten small group meetings with caregivers and individual patients outlining the most serious symptoms of SSADH to be highlighted at the Externally-Led Patient Focused Drug Development (EL-PFDD) meeting.

2021 – Nine manuscripts have been published from the July, 2020 SSADH International On-Line Conference in the Journal of Child Neurology.

2021 – An Additional $55,000 was awarded to Henry Lee, PhD & Alexander Rotenberg MD, PhD at Boston Children’s Hospital in July of 2021 to evaluate three critical aims (rate, age and location) for ERT using the mouse model. This is a critical step in the discovery process for understanding the viability of ERT for SSADH patients.

2021 – We were granted approval from the FDA to hold a Patient Focused Drug Development (PFDD) Meeting on July 8^th 2022, in preparation for initiating an enzyme replacement trial for SSADH.

2021 – We have exceeded the recruiting requirements for the SSADH Natural History Study going on at Boston Children's Hospital in the United States, Heidelberg University Hospital in Germany and at the Hospital Saint Joan de Déu in Barcelona, Spain.

2021 – SSADH Association committed $12,000 to maintain a Backup SSADH Mice Colony at JEX Services to ensure the availability of SSADH Mice should something happen to the existing colony at Washington State University, preventing any lapse in research due to the lack of SSADH mice.

2021 – $50,000 was awarded to Jens Andersen, PhD at the University of Copenhagen, Denmark as a fellowship grant to evaluate the Molecular Pathological Mechanisms of CaMK2a in SSADH Deficiency under the guidance of Petrine Wellendorph, PhD, an international leader in the neuroscience community related to GHB/GABA research. 

2020 – Hosted Virtual SSADH Conference with 300 individual registrations representing 25 countries.

2020 - Created a SSADH Deficiency Investigators Consortium (SDIC) made up of medical professionals and interested parties who have committed to collaborate on SSADH research.

2020 - $100,000 was awarded to Phillip Pearl, MD & Alexander Rotenberg MD, PhD at Boston Children’s Hospital in May of 2020, to develop a SSADH mouse model to e used to test the prospect of Enzyme Replacement Therapy.

2020 – Rinaldo, Piero, M.D., Ph.D., Vice Chair Information Management, Department of Laboratory Medicine and Pathology, Mayo Clinic, MN., and Dr. Mike Gibson, Ph.D., FACMG have completed the  algorithm for detecting SSADH at birth from a drop of blood. This is a monumental step for SSADH and imperative to be considered for the Newborn Screen Panel.

2020 – Sarah Elsea, Ph.D., FACMG Professor, Dept. of Molecular and Human Genetics and Senior Director Biochemical Genetics at Baylor College of Medicine has documented the genomic
variants for SSADH and believes the disease incident rate is 1:330,000. 

2020 – We have nearly reached the recruiting requirements for the SSADH Natural History Study going on at Boston Children's Hospital in the United States, Heidelberg University Hospital in Germany and at the Hospital Saint Joan de Déu in Barcelona, Spain.

2020 – SSADH Association committed $12,000 to maintain a Backup SSADH Mice Colony at JEX Services to ensure the availability of SSADH Mice should something happen to the existing colony at Washington State University, preventing any lapse in research due to the lack of SSADH mice.

2019 – the Center for Disease Control and Prevention (CDC) has issued an ICD-10-CM code E72.81 Disorders of gamma aminobutyric acid metabolism, specifically for SSADH.  This will allow medical professionals to code a patient visit for SSADH. 

2018 – Dr. Gibson was awarded $686,980 from a grant through the NIH to conduct a Natural History Study which will be of great value for future research and for the FDA drug approval process. The Natural History Study will aim to determine the natural evolution and the clinical presentation of SSADH with yearly neurological and neuropsychiatric assessments.

2018 – SSADH Association has awarded $12,000 to Ritva Tikkanen, MD, PhD from Justus-Liebig Universität Gießen, Germany to create molecular consequences of SSADH mutations allowing for mutation specific therapies. Dr. Tikkanen will be using the SSADH stem cell lines created at Boston Children’s Hospital. 

2018 – SSADH Association committed $10,000 to maintain a Backup SSADH Mice Colony at JEX Services to ensure the availability of SSADH Mice should something happen to the existing colony at Washington State University, preventing any lapse in research due to the lack of SSADH mice.

2018 – SSADH Association awarded $125,000 to Phillip Pearl, MD & Mustafa Sahin MD, PhD at Boston Children’s Hospital and Harvard Medical School in addition to an anonymous $175,000 donation on behalf of the Boston Children’s Hospital Trust.  This project will be a continuation of our initial funding from 2015 to create SSADH stem cells and heterozygous controlled GABA’ergic iPSC lines. The goal of this phase will be to use the patient iPSC neurons to screen for novel therapeutic approaches to treatments.

2017 – SSADH Association committed $10,000 to establish a Backup SSADH Mice Colony at JEX Services to ensure the availability of SSADH Mice should something happen to the existing colony at Washington State University, preventing any lapse in research due to the lack of SSADH mice.

2017 – SSADH Association awarded $305,616 to K. Michael Gibson, PhD, FACMG at Washington State University for the SSADH Biorepository project which aims at creating a biobank where biospecimens and matching clinical data are collected longitudinally from all interested: patients, siblings and family members, unaffected, age-matched control individuals. The Biorepository will be created over the next five years with the following team:  Drs. Gibson and Roullet, (WSU), Dr. Pearl (BCH), Dr. Opladen (iNTD, Heidelberg, Germany) and the SSADH Association.

2016 – SSADH Association committed $10,000 to kick off a Natural History Study with the US medical team of Phil Pearl, MD, (Boston Children's Hospital), Jean-Baptiste Roullet, PhD, and Mike Gibson, PhD, FACMG, (both from WSU), together with Evangeline Wassmer, PhD (UK), Thomas Opladen, MD, (Germany) and Garcia-Cazorla, PhD, (Spain) will work with the SSADH Association on a grant proposal to support a multi-year (5+) and multi-site natural history study of SSADH patients.

2016 – SSADH Association awarded $100,000 to Phil Pearl, MD & Robin Kleiman, PhD, to fund a one year research grant in conjunction with Boston Children’s Hospital. The objective of this project is to develop an in vitro disease model of SSADH Deficiency from patient iPSC lines differentiated into GABAergic neurons that will support phenotypic drug screening.

2016 – Preclinical NCS-382 studies; vigabatrin ocular toxicity in SSADH

2015 – Investigation of the immunological response in SSADH cells by Karen Newell-Rogers, PhD at Texas A&M to understand the alterations in metabolism and immunity using the SSADH mouse model.

2015 – Evaluation of Metabolites in SSADH Urine is being studied by Dr. Kara Vogel at Washington State University to explore possibilities for SSADH patients.

2015 – SSADH Association awarded $5,000 was awarded to Kestutis G. Bendinskas, PhD at SUNY-Oswego to develop an easy to use field colorimetric assay screen to detect the biomarker for SSADH deficiency gamma hydroxybutyric acid (GHB), in either urine or saliva to screen candidates. 

2015 – SSADH Association awarded $100,000 to K. Michael Gibson, PhD, FACMG at Washington State University to garner efficacy data in the SSADH deficient animal model to form the framework for the Investigational New Drug Application with the NIH for the use of compounds NCS-382 and HOCPCA.

2015 – SSADH Association awarded $158,950 to the University of California, San Diego to determine if the induction of autophagy by rapamycin would remove surplus organelles, thus reducing oxidative stress and restoring cellular homeostasis which may lead to potential treatments for SSADH deficiency.

2010 – Dr. Gibson is awarded a $50,000 grant from the PND Association towards SSADH deficiency entitled “Efficacy of Ornithine Alpha Ketoglutarate Intervention in SSADHD“.

2011 – The NIH receives a $45,000 grant from the SSADH Association towards the encapsulation of
SGS-742, a medication that will be studied in a NIH Clinical Research Study.

2012 – Human GABA_BR dysfunction using transcranial magnetic stimulation

2013 – Testing of an experimental drug’s effectiveness on SSADH has been funded by a $743,974 grant from the National Institutes of Health to Dr. Gibson Washington State University professor.

2013 – SSADH Association awards $79,500 Fellowship Research Grant to Ronak Lakhani, PhD at the University of California, San Diego to understand the use of rapamycin and other autophagy-inducing drugs for treating SSADH deficiency.

2014 – NIH Clinical Trail of Taurine to combat the impact of SSADH complete.

2014 – NIH Phase 2 Clinical Trial of SGS-742 Therapy Recruiting SSADHD Patients

2014 – SSADH Association awards an additional One Year Research Grant to Ronak Lakhani, PhD at the University of California, San Diego to determine if the induction of autophagy by Rapamycin would remove surplus organelles, thus reducing oxidative stress and restoring cellular homeostasis which may lead to potential treatments for SSADH Deficiency.

2005 – NIH Clinical Research Study “Cortical Excitability in SSADHD Patients”

2005 – NIH Clinical Research Study “PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase Deficiency”

2006 – NIH Clinical Research Study “Taurine and its effect on SSADH patients”

2008 – Identification of metabolic disruptions in embryonic KO mice

2008 – Rescue of KO mice with the ketogenic diet

2009 – Human GABA_BR dysfunction using 11C-flumazenil binding

2009 – Crystal structure of human SSADHD; Dynamic Catalytic Loop

2009 – Efficacy of SGS-742 (GABA_BR antagonist) in KO mouse

2000 – Dr. Gibson is awarded a $6,000 grant from the PND Association contributing towards his GHB Research Fund.

2001 – Dr. Gibson developed a murine knockout (KO) model of SSADHD.

2003 – Compilation of 27 disease-associated mutations in SSADHD.

2004 – Dr. Phil Pearl is awarded a $30,000 grant from the PND Association to add a research fellowship towards developing an SSADH clinical profile and database.

2004 to 2006 – Definition of KO mouse seizure profile; GABA_BR / GABA_AR abnormalities

2004 to 2005 – Dr. Gibson asked to present the 10th Annual Komrower Commemorative Lecture, the key invited talk, at the Annual Meeting of the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Meeting in Amsterdam, with a talk entitled “Gamma-Hydroxybutyric Aciduria: A Biochemist’s Education from a Heritable Disorder of GABA Metabolism”

1995 – Composite clones encoding mature rat brain SSADHD predicted a protein with 488 amino acids, consistent with Dr. Gibson’s purified protein data. The cDNA clones were confirmed by expression of enzyme activity in bacteria, and the human gene was mapped to chromosome 6p22, spanning some 38 kb of genomic DNA.

1995 to 1998 – Molecular cloning of ALDH5A1 gene; Identification of Mutations

1997 – Genotype/phenotype correlations in 23 patients; case histories

1999 to 2009 – Dr. Mike Gibson and Dr. O. Carter Snead are funded continuously by the NIH for their R01 studies on the mouse model of 4-hydroxybutyric aciduria (project entitled “Pathophysiology and Treatment of Inherited Gamma-Hydroxybutyric Aciduria in the Mouse”.

1990 – Dr. Gibson employs a fluorometric assay and isotope dilution method for GHB which facilitated prenatal diagnoses, using parallel investigations of metaboloites in amniotic fluid with enzyme measurement in amniocytes and chorionic villus tissue.

1992 – Dr. Gibson began to purify mammalian SSADHD with the goal of cloning the gene and determining whether patients harboured mutations. His laboratory developed a new purification scheme for isolation of rat brain SSADHD, combining ion-exchange and affinity chromatography steps to purify the protein to apparent homogeneity.

1993 – Prenatal Detection of SSADHD; Identification of CNS Enzyme Defect

1987 – Dr. Garry Brown identifies DHHA in the urine of SSADHD patients using GCMS

1985 to 1990 – Dr. Gibson focuses his time on identifying patients, developing improved assay methods for enzyme and metabolite quantitation, performing the infrequent prenatal diagnosis, and beginning to outline the cloning of mammalian SSADHD.

1981 – Dr. Cornelis Jakobs identified a mentally retarded boy with minimal language development. Urine organic acid analysis of this child revealed an increased quantity of gamma hydroxybutyric acid (GHB), a compound that had not previously been identified in human urine. Dr. Jakobs postulated that this child had an inherited defect in the metabolism of GABA.

1982 – Dr. K. Michael Gibson alters career path to pursue documenting the enzyme defect in Dr. Jakob’s patient. During this time, Dr. Gibson drew his own blood to look for SSADH activity in white-cell extracts which provided a method and a peripheral tissue source in which to document the enzyme defect in the first three SSADH patients, and began a long journey in the investigation of this rare disorder.