Author: Jacob Tiller
Here at SLC6A1 Connect, we believe that each family deserves access to accurate and understandable information related to their childrens’ conditions. Please find the link to our “Parental Overview” here- Scientific Overview.
In addition to this condition overview covering the scientific foundations of the SLC6A1 genetic mutation, we have provided information on relevant research and experts in the field.
Scientific Information
The foundations of the 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-
- Current SLC6A1 Knowledge- Dr. Kimberly Goodspeed
- Phenotypic SLC6A1 Mutations- Dr. Katrine Johannesen
- 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.
Leaders in the Field
- Stephen Lisberger (PhD), in the neurobiology department at Duke University. His lab is directed towards investigating how the brain learns motor skills, and how we utilize what we see to guide movement. This aligns perfectly with Maxwell’s condition, as he is young and still developing motor/visual skills.
Contact Information: lisberger@neuro.duke.edu and 919-681-7088 - Maurizio Corbetta (MD), is in the neurology department at Washington University St. Louis. His lab is directed towards analyzing the neural basis of cognition through the scope of vision and attention. His work aligns extremely well with Maxwell’s condition, as he is investigating the neurological basis of selecting and responding to stimuli. He is also coordinating a large study into neuronal communication, which is related to the issues with inhibition that Maxwell experiences. This study is housed in Europe and involves eight different countries. I did find the phone number of his overall lab.
Contact Information: 314-362-4503 - Anne Connolly (MD) is the chief of the Division of Neurology at Nationwide Children’s Hospital. She is also a member of the Center for Gene Therapy at the Abigail Wexner Research Institute. Her research has largely been focused on examining the relationship between auto-antibodies and childhood neurological disorders. She has also led studies in examining the relationship between genetic causes of muscular dystrophy and neuromuscular disorders in children. Her research aligns perfectly with Maxwell’s condition and she has ties to both universities and private labs.
Contact Information: 614-722-4625 - David Clifford (MD) is the Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology at Washington University in St. Louis. His primary focus has been improving and developing medicinal/pharmaceutical therapeutics for neurological disorders. Despite Horizon giving in, it may still prove useful to have someone on board that is involved in the pharmaceutical world.
Contact Information: 314-747-8423