Scientific Information

The foundations of SLC6A1 are based on how the 1st member of the 6th solute carrier family is a gene that encodes for the GABA transporter protein type 1, which is vital for the proper reuptake of the GABA neurotransmitter, which is responsible for extracellular inhibition in the nervous system. This may sound complicated, but GABA as a neurotransmitter is essentially in charge of balancing neuronal excitation and keeping neurons from being overactive. Without this proper balance, the symptoms of SLC6A1 such as intellectual delays and seizures arise.

Let’s break this transport interaction down more. Gamma-amino butyric acid (GABA) is vital for brain metabolism and overall function. Glutamate is also a vital amino acid for brain function across the board. These two amino acids also act as neurotransmitters, with GABA acting as an inhibitory force in the brain. It will often occupy receptors on neuronal surfaces to prevent chemicals from binding to these receptors and catalyzing reactions. Glutamate, however, is an excitatory neurotransmitter that promotes activity and reception within the brain. The foundation of these two neurotransmitters is glutamine, which acts as the substrate for the production/generation of both GABA and glutamate. With SLC6A1, the balance of GABA and glutamate is skewed.

More Information On These Genetic Transport Mechanisms Can Be Found Here:

  1. Current SLC6A1 Knowledge : Dr. Kimberly Goodspeed
  2. Phenotypic SLC6A1 Mutations : Dr. Katrine Johannesen
  3. SLC6A1 Connect Journal Database : Dr. Dennis Lal

Although SLC6A1 currently has no known cure, there are promising treatment options offering mitigation of symptoms. In other words, there is no cure yet, but there are ways to minimize symptoms. Perhaps the most promising of these that may yet develop into a treatment method is gene therapy. This works by packing a functional gene into a viral vector and then inserting this vector into a patient. Once inside, the functioning gene will be released from the vector and will “replace” the malfunctioning gene of the patient.

Treatment Options

Here is an interesting paper on gene therapy being applied to restore dopamine transport deficits that were caused by the SLC6A3 genetic mutation. Although this is not the same condition as SLC6A1, it does show that genetic therapy can be effective in reducing symptoms and restoring genetic function. Find the link to this paper here- Gene Therapy Example.

In addition to resources such as this paper, use the link below to learn more about the gene therapy work conducted by one of our affiliate organizations, the Nationwide Children’s Hospital. Find this link here- Nationwide Children’s Hospital Information.

Along with gene therapy, glycerol-phenylbutyrate has also been used as an effective drug treatment for the mitigation of SLC6A1 symptoms.
Find that report here- Glycerol Phenylbutyrate.


Scientific Advisor

Vincenzo Crunelli

FMedSci, FAcadEur, FLSW

Vincenzo Crunelli is Professor of Neuroscience at Cardiff University (Cardiff, UK) and Visiting Professor at the Institute of Pharmacology and Neuroscience, University of Lisbon (Lisbon, Portugal). He got his PhD at the University of Catania (Catania, Italy) and his postdoctoral training included research fellowships at the M. Negri Institute (Milan, Italy), the Weizmann Institute (Rehovot, Israel) and the MRC Neuropharmacology Unit (Cambridge, UK). He was Head of the Department of Physiology and the Neuroscience Division at Cardiff University, and was Editor-in-Chief of the Journal of Neuroscience Methods. In recognition of his work on epilepsy and sleep, he was elected Fellow of the Academic of Medical Sciences (UK), the Academia Europaea and the Learned Society of Wales (UK).

Vincenzo Crunelli research focuses on the cellular and network mechanisms of EEG waves of non-REM sleep and the pathophysiology, comorbidities and pharmaco-resistance of absence seizures. His labs in Cardiff and Lisbon use a sophisticated combination of state-of the-art techniques in normal and transgenic models which span from optogenetics and silicone probe recordings to two photon laser scanning confocal microscopy and non-invasive imaging. Currently, his research group aims to identify astrocytic and neuronal targets that control both absence seizures and their cognitive and memory comorbidities, using in vivo recordings in animal models and MRI spectroscopy in children/teenagers with absence seizures.

Recommended Doctors

Scott Demarest, MD

Children’s Hospital of Colorado
Denver, Colorado USA

Katrine Johannesen, MD

Danish Epilepsy Centre
Dianalund, Denmar

Professor Deb Pal

King’s College London
London, UK

Annapurna-Poduri, MD

Boston Children’s
Boston, Massachusetts USA

Prof Ingrid Scheffer

The University of Melbourne
Melbourne, Australia

Pam McDonnell, MD

Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania USA

Dr. J.S. (Judith) Verhoeven

Academic Center for Epileptology Kempenhaeghe
Heeze, The Netherlands

Constance Smith-Hicks, MD PhD

Kennedy Krieger Institute
Baltimore, Maryland USA

This is the alpha version of the SLC6A1 Portal

The SLC6A1 Portal is a coalition of investigators seeking to aggregate and harmonize data generated to study SLC6A1-related disorders, and to make summary data interactively accessible for the wider scientific community, while providing educational resources for everyone. The goals of this project are:

  • Providing information on SLC6A1-related disorders
  • Supporting research on SLC6A1-related disorders
  • Facilitating recruitment of individuals to the global SLC6A1 registries
  • Providing support in variant interpretation and classification
  • Visualizing data from the global SLC6A1 registries
  • Linking researchers, clinicians and families

The SLC6A1 Portal is an ongoing project of the scientific community in collaboration with SLC6A1Connect. Interested collaborators are invited to reach out to join the project.