Amber Freed, Founder & CEO of SLC6A1 Connect, advocates for research into the SLC6A1 gene, where loss of function polymorphisms are implicated in monogenic epilepsy, autism, and various other neurological and psychiatric disorders. SLC6A1 encodes GABA transporter 1 (GAT1), which plays a crucial role in maintaining the neuronal excitatory-inhibitory balance through the reuptake of inhibitory neurotransmitter GABA. SLC6A1 polymorphisms result in dysfunctional GAT1 and disrupt its trafficking to neuronal membranes. SLC6A1 Connect was founded by Freed in 2018 after her son was diagnosed with monogenic epilepsy due to mutations in the SLC6A1 gene. The organization is dedicated to advancing curative approaches for this disease, including gene replacement therapy and small molecule drug discovery to correct the functioning of GAT1. SLC6A1 Connect has made significant strides, and they continue to raise awareness and funds to advance scientific research that will ultimately result in a cure for patients with SLC6A1 polymorphisms. This interview took place at the International Epilepsy Congress (IEC) 2023 in Dublin, Ireland.
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Transcript (edited for clarity)
SLC6A1 is a monogenic, haploinsufficient loss-of-function. What does that mean? Well, it means we’re a candidate for gene replacement therapy using AAV9, tried and true in clinic. It also means that we’re a candidate for up-and-coming gene therapies that maybe use a more sophisticated capsid. We are also a candidate for antisense oligonucleotides, and technology has just blown me away in the past couple of years at how quickly that is moving...
SLC6A1 is a monogenic, haploinsufficient loss-of-function. What does that mean? Well, it means we’re a candidate for gene replacement therapy using AAV9, tried and true in clinic. It also means that we’re a candidate for up-and-coming gene therapies that maybe use a more sophisticated capsid. We are also a candidate for antisense oligonucleotides, and technology has just blown me away in the past couple of years at how quickly that is moving. And lastly, we are a unique epilepsy in the sense that not only are we missing 50% of a GAT1 transporter, which carries the body’s most important inhibitory neurotransmitter, we also have trafficking stress within our cells. The protein gets stuck in the endoplasmic reticulum, so it makes us attractive as a small molecule drug discovery target.
I founded SLC6A1 Connect in 2018 when my son Maxwell was diagnosed with the disorder. We are a patient advocacy group dedicated to advancing curative approaches for this disorder by raising awareness and fundraising for research purposes. Since that time, we’ve created two registries, a natural history study, we’re working with 20 academic institutions, and now numerous biotechs to advance treatments. We’ve repurposed a drug that is helping our community and we’re advancing numerous translational approaches. We spend every waking moment dedicated to advancing research. We believe that time is not on our side and that the historical, long timeline of drug development just isn’t going to work for our kids. They need help now and we take that attitude into our advocacy.
The other very important thing to mention about SLC6A1 is that when Maxwell was diagnosed, we thought it was an ultra-rare genetic epilepsy and that couldn’t be further from the truth. We actually just weren’t on the right testing panels. In reality, we’re the sixth highest cause of epilepsy, the 10th highest cause of autism, and we play a leading role in major psychiatric disorders like ADHD, schizophrenia, and bipolar disorder. So, we started with a very small population, but we’ve just exploded into being a profitable target for a biotech company through advocacy. And this is a story of a lot of monogenetic epilepsies. Right now, we’re finally at this moment in time where there is a solution, and we can bring drugs to market to help our children in our lifetime.