Targeting the Gut-Immune-Brain Axis
Our bodies are home to trillions of microbes that impact our health. We’re comprised of microbial cells, and advancing research is uncovering the role that these microbes play in regulating brain behavior, development and function.
The gut-immune-brain axis is a multi-directional signaling network between the microbiota in the gastrointestinal tract, the immune system, and the brain. Complex pathways of the resident microbes and host systems interact to drive function in the cognitive and emotional centers in the brain.
Microbes modulate neuroinflammation as well as host levels of neuroactive molecules, including neurotransmitters and neuropeptides, that affect complex behaviors, such as social, communicative, emotional, and anxiety-like behaviors.
There is increasing data to understand how the gut microbiota influences and contributes to the pathogenesis of many neurological disorders. In many cases, alterations in the microbial communities that inhabit us are further implicated in positive responses to treatment in a variety of neurological disorders, including epilepsy, Amyotrophic Lateral Sclerosis (ALS), dementia, and Alzheimer’s.
Microbiome therapeutics are multifunctional in nature and can target multiple pathways simultaneously.
IrisRx™: Our Breakthrough, Proprietary Platform
Bloom Science’s therapeutic discovery and development platform, IrisRxTM, is enabling us to pioneer the next frontier of living medicines to transform the quality of life for patients with neurological diseases worldwide.
We understand that neurological conditions are multi-functional. By targeting the multidirectional axis between the gut microbiome and the CNS, the likelihood of addressing the underlying dysfunction of the disease is much higher.
Because we start with responder data and reverse engineer into novel microbiota drug candidates, our platform is designed to deliver higher translatability and clinical success.
Bloom is developing live medicines and diagnostics for brain-gut microbiome interactions in neurological diseases and conditions, including:
- Seizures and Epilepsy
- ALS also known as Lou Gehrig’s disease
Treatment of Seizures
Bloom’s BL-001, an orally-administered live biotherapeutic product (LBP), is in human trials, to treat drug-resistant seizures in patients with Dravet syndrome and other developmental and epileptic encephalopathies. Dravet is a rare epilepsy syndrome that begins in infancy or early childhood and causes developmental challenges in childhood.
This therapeutic candidate is designed to replicate the metabolic profile of validated ketogenic diets and thereby alter the metabolic processing of key biochemicals. In doing so, BL-001 is the only Dravet syndrome therapy to directly increase the biosynthesis of gamma aminobutyric acid (GABA), a neurotransmitter implicated in various seizure disorders including Dravet syndrome.
We have also shown that BL-001 also restores impaired bioenergetics and mitochondrial function and reduces neuroinflammatory signals in animal models. BL-001 is set to enter the clinic, with a phase 1 clinical trial in early 2023.
Treatment of Amyotrophic Lateral Sclerosis (ALS)
Bloom is also using its novel approach to treat patients with ALS, a disease that causes nerve cells to die, which breaks the neural pathways, and causes extreme mobility loss over time. This disease can develop at any time, but is more common in people over 60 years old.
BL-002 is built on evidence that oxidative stress drives ALS by causing the loss of motor neurons and the dysfunction of mitochondria.Nicotinamide, an important NAD+ pathway metabolite and a derivative of vitamin B3, can counter the effects of ALS.
BL-002 produces this vitamin and Bloom has shown it attenuates motor-neuron loss, and increases lifespan and motor coordination, in ALS model mice.
Building on the Platform
Bloom’s programs have the potential to address major unmet medical needs and lay the groundwork for second-generation candidates that will benefit from Bloom’s explorations of how to enhance the endogenous functions and properties of bacteria.
Our focus on engineering commensal bacterial consortia and strains found in the mucosal layer of the gut gives us advantages over other synthetic-biology startups and creates drug candidates with superior efficacy, safety and drug-like properties.