Neurology
The exRNA Therapeutics Department of Neurology is at the forefront of groundbreaking research and drug development of Parkinson’s disease, Alzheimer’s disease, Epilepsy and schizophrenia. Our focus is on uncovering the genetic underpinnings of these conditions and pioneering advanced therapies to combat them. One of our most exciting innovations is Antisense Oligonucleotide (ASO) therapy, a cutting-edge approach that targets genetic disorders at the RNA level. This therapy utilizes synthetic nucleic acid strands designed to precisely bind to specific RNA molecules, thereby modifying their function and regulating gene expression. By harnessing the power of ASO therapy, we aim to transform the landscape of neurological treatment and offer hope to patients worldwide.
Parkinson's Disease
Parkinson's disease (PD) is characterized by motor symptoms such as tremors, rigidity, bradykinesia (slowness of movement), and postural instability. These arise due to the progressive degeneration of dopamine-producing neurons in the substantia nigra region of the brain. The molecular mechanisms underlying PD involve complex interactions between genetic predispositions, environmental factors, and abnormal protein aggregation (e.g., alpha-synuclein) leading to neuronal dysfunction and death. ASO (antisense oligonucleotide) therapy holds potential in PD treatment by targeting specific genes involved in disease pathology. ASOs can selectively bind to RNA transcripts, thereby modulating gene expression to reduce abnormal protein production or enhance clearance of toxic aggregates like alpha-synuclein. This approach aims to mitigate neuronal damage, improve motor function, and possibly slow disease progression. exRNA Therapeutics drug for Parkinson helps in managing symptoms and potentially altering the course of the disease by addressing underlying molecular abnormalities.
Genes Under Investigation
SNCA (Alpha Synuclein): SNCA gene encodes alpha-synuclein, a protein abundant in the brain and implicated in synaptic function. In Parkinson's disease (PD), alpha-synuclein misfolds, forming toxic aggregates called Lewy bodies, which spread between neurons. SNCA mutations are linked to familial PD, increasing alpha-synuclein expression or promoting aggregation. Pathophysiological mechanisms include protein aggregation, mitochondrial dysfunction, synaptic disruption, neuroinflammation, and cell-to-cell transmission. Therapeutic strategies include gene silencing, immunotherapy, small molecule inhibitors, and neuroprotective therapies targeting alpha-synuclein. Understanding SNCA's role in PD informs the development of targeted therapies, including antisense oligonucleotides, immunotherapies, inhibitors of aggregation, and neuroprotective agents. This ongoing research aims to mitigate alpha-synuclein-induced neuronal damage, advancing PD treatment.
Alzheimer's Disease
A neurodegenerative condition called Alzheimer's disease (AD) is a steadily worsening illness that affects memory and other critical mental processes..The hippocampus, a part of the brain essential for memory encoding, and other areas of the cerebral cortex involved in thought and decision-making.The enzyme acetylcholinesterase hydrolyzes the neurotransmitter acetylcholine, which is critical for learning and memory. In the brain, AChE is found at cholinergic synapses and neuromuscular junctions. The primary function it performs is hydrolyzing acetylcholine into choline and acetate, which the neuron subsequently recycles to halt synaptic firing. Acetylcholinesterase is crucial to the pathogenesis of Alzheimer's disease because it plays a role in both the formation of amyloid plaques and the breakdown of acetylcholine.When AChE is suppressed, acetylcholine levels are elevated, which can improve cognitive function and postpone the onset of Alzheimer's disease symptoms. With the development of our ExRNA-based ACHEI drug, provide patients with a safer and more effective medication that will ultimately enhance their quality of life and cognitive performance. As we conduct our research and development efforts, we are committed to closing the gaps in Alzheimer's treatment and bringing us closer to a day when effective management and perhaps even disease modification are possible.
Genes Under Investigation
PSEN1 & 2
PSEN1 and PSEN2 genes encode presenilin proteins integral to the gamma-secretase complex, crucial for cleaving proteins like amyloid precursor protein (APP) linked to Alzheimer's disease. While primarily associated with Alzheimer's, their role in Parkinson's disease (PD) is under investigation. PD is marked by dopaminergic neuron loss and alpha-synuclein accumulation. Potential links between presenilins and PD include protein processing, calcium regulation, mitochondrial dynamics, and autophagy. Direct evidence is limited, but mutations in PSEN1 and PSEN2 may influence PD risk or phenotype. Further research is needed to elucidate their role in PD pathology. Understanding presenilins' involvement in PD could offer insights into disease mechanisms and potential therapeutic targets.
BACE1 (Beta-Secretase 1)
BACE1 (Beta-Secretase 1) gene encodes an enzyme crucial for Alzheimer's disease (AD) pathology by initiating amyloid-beta (Aβ) peptide production from amyloid precursor protein (APP). Aβ accumulation leads to plaque formation and neurotoxic effects, contributing to synaptic dysfunction and neuronal death in AD. BACE1 inhibitors aim to mitigate Aβ levels, but clinical trials face challenges in efficacy and side effects. Genetic studies explore BACE1 variants' association with AD risk, while BACE1 activity serves as a potential biomarker for disease progression and treatment response. Understanding BACE1's role offers insights into AD pathogenesis and therapeutic strategies.
CHRNA7
The CHRNA7 gene encodes the alpha-7 subunit of the nicotinic acetylcholine receptor (nAChR), implicated in learning and memory. In Alzheimer's disease (AD), CHRNA7 dysfunction may contribute to cognitive decline through synaptic plasticity disruption. Alpha-7 nAChRs also play a role in neuroprotection and amyloid-beta peptide interactions, influencing AD pathology. Genetic studies show mixed associations between CHRNA7 polymorphisms and AD risk, while postmortem and preclinical research suggests altered receptor expression in AD brains. Therapeutically, alpha-7 nAChR agonists aim to improve cognitive deficits, yet clinical trials show varied results. Establishing CHRNA7 as a biomarker could aid in AD diagnosis and monitoring. Understanding CHRNA7's role offers insights into AD pathophysiology and potential therapeutic avenues.
Epilepsy
Epilepsy presents with recurring seizures characterized by abnormal electrical activity in the brain, often accompanied by convulsions, loss of consciousness, or unusual sensations. The molecular mechanisms involve disruptions in ion channels, neurotransmitter systems (such as GABA and glutamate), and genetic mutations affecting neuronal excitability and synchronization. ASO (antisense oligonucleotide) therapy offers a promising strategy by targeting specific genes implicated in epilepsy pathophysiology. ASOs can bind to RNA transcripts, modulating gene expression to correct abnormal protein production or regulation associated with seizure activity. This approach aims to normalize molecular pathways involved in epileptogenesis, potentially reducing seizure frequency and severity. ASO treatment represents a targeted therapeutic approach that could significantly improve seizure control and quality of life for individuals with epilepsy, offering hope for managing the disease and potentially altering its progression by addressing underlying molecular abnormalities.
Genes Under Investigation
CHRNA7
The CHRNA7 gene encodes the alpha-7 subunit of the nicotinic acetylcholine receptor (nAChR), vital for synaptic transmission and plasticity. In epilepsy, CHRNA7's involvement is linked to its impact on neuronal excitability, synaptic plasticity, and neuroinflammation. Genetic studies have identified CHRNA7 variants associated with epilepsy risk, while animal models reveal its dual role in seizure modulation. Pharmacological agents targeting alpha-7 nAChR show promise in preclinical studies. Understanding CHRNA7's role may lead to novel epilepsy treatments, with drugs modulating its activity offering potential seizure control. Personalized medicine approaches, such as genetic testing for CHRNA7 variants, could enable tailored therapies for individuals with epilepsy, advancing treatment efficacy.
KCTD12
KCTD12, associated with GABA_B receptor modulation, may influence epilepsy pathophysiology. Its impact on GABAergic inhibition suggests involvement in seizure development. KCTD12's modulation of GABA_B receptor kinetics may disrupt the excitatory-inhibitory balance, potentially increasing seizure susceptibility. Additionally, by affecting synaptic plasticity, KCTD12 could contribute to aberrant neural circuit formation related to seizures. While not extensively studied in epilepsy genetics, KCTD12 warrants investigation for its role in inhibitory pathways. Functional studies, particularly in animal models, could clarify its significance. If validated, KCTD12 might serve as a target for antiepileptic drug development, aiming to enhance inhibitory signaling. Furthermore, understanding its role could lead to epilepsy biomarker development for improved diagnosis and treatment prediction.
KCNT1
The potassium channel subfamily T member 1 (KCNT1), sometimes referred to as Slack (sodium-activated potassium channel), is encoded by KCNT1, one of several genes that has been linked to epilepsy. KCNT1 is a prime candidate for investigation and treatment because mutations in it have been linked to a number of severe forms of epilepsy. Specifically, our medication provide potential method targets and modifies the expression of the mutant KCNT1 gene by using antisense oligonucleotides (ASOs).
Schizophrenia
Schizophrenia is characterized by psychotic symptoms such as delusions, hallucinations, and thought disorders (abnormal ways of thinking), as well as decreased emotional expression, decreased drive to achieve goals, trouble forming social relationships, impairments to motor function and cognitive function. The molecular mechanisms underlying schizophrenia involve complex interactions between genetic, neurodevelopmental, and environmental factors affecting neurotransmitter systems (like dopamine and glutamate) and brain structure. ASO (antisense oligonucleotide) treatment offers a promising avenue by targeting specific genes implicated in schizophrenia pathology. ASOs can modulate gene expression by binding to RNA transcripts, thus potentially correcting abnormal protein production or regulation linked to the disorder. This approach aims to normalize molecular pathways disrupted in schizophrenia, potentially mitigating symptoms and halting disease progression.
Genes Under Investigation
CHRNA7
CHRNA7 encodes the alpha-7 subunit of nicotinic acetylcholine receptors (nAChRs) crucial for fast signal transmission in synapses. These receptors modulate neurotransmitter release and synaptic plasticity, influencing cognitive processes like learning and memory. They also play roles in neuroprotection and neurodevelopment. CHRNA7 alterations are associated with schizophrenia, Alzheimer's, bipolar disorder, and ADHD. Therapeutically, CHRNA7 is a potential drug target for cognitive deficits in these disorders. It may serve as a biomarker for diagnosing and tracking disease progression. Understanding its function sheds light on neurological disorders and potential treatments.
KCTD12
KCTD12 is a gene encoding a protein involved in regulating potassium channels and modulating the GABA_B receptor, crucial for inhibitory neurotransmission. It influences receptor kinetics and surface expression, impacting neuronal development and sensory processing, particularly in the auditory system. In cancer, KCTD12 downregulation, observed in pancreatic cancer, may correlate with poor prognosis, implicating its role in cell proliferation and apoptosis regulation. While its direct involvement in neurological disorders remains unclear, its association with GABA_B receptors suggests relevance in disorders with GABAergic dysfunction. Understanding KCTD12's role could lead to novel treatments for such conditions. Its expression levels in cancer hold potential as biomarkers for diagnosis or prognosis, though further research is necessary for clinical validation.
CACNA1C
CACNA1C is a gene that encodes the alpha-1C subunit of the L-type voltage-dependent calcium channel (Cav1.2). This channel is crucial for the influx of calcium ions into cells, which is essential for various cellular processes including muscle contraction, neurotransmitter release, and gene expression.CACNA1C has been identified as one of the genetic risk factors for schizophrenia. One prospective therapeutic approach for the treatment of schizophrenia is the creation of an antisense oligonucleotide that targets CACNA1C. This method attempts to rectify the underlying problems in calcium signaling linked to the illness by selectively decreasing the expression of CACNA1C. Therefore, the goal of our continued research and development is to optimize the ASO's therapeutic efficacy, delivery, and design in order to eventually offer patients with schizophrenia a cutting-edge and efficient treatment.