Unraveling the Biology of Rare Neurological Disorders
At Nospharma, we have a deep understanding of the crucial role biological pathways play in neurological disorders. By coupling emerging science with novel patient-focused clinical endpoints, we develop innovative medicines that tackle the pathology of rare genetic neurological conditions.
We aim to treat the key pathologies of rare genetic disorders with a single treatment that consists of multiple small-molecules and peptides.
By using a multi-therapeutic approach for a disorder, with each targeting a unique biological underpinning of the condition, we are making medicines with enhanced effectiveness.
Genetic Disorders
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Fragile X syndrome (FXS) is a rare genetic disorder where affected individuals have neurodevelopmental delay and life-long neurological symptoms like intellectual disability, autistic behaviors, speech and motor disorders, sleep problems, ADHD, and anxiety.
The genetic cause of FXS is the hyper elongation of the CGG trinucleotide sequence of the FMR1 gene located on the X-chromosome. Typically, the FMR1 gene allows neurons to make FMRP, a protein that is essential for normal brain development. In people with FXS, the abnormal length of the CGG repeat causes the FMR1 gene to shut down, resulting in a loss of FMRP production and function.
Today, 1 in every 4,000 males and 1 in every 8,000 females has FXS, making it the leading monogenic cause of autism and responsible for ~50% of all X-linked intellectual disability cases. Yet, there is no cure for FXS, with current interventions only partially improving some symptoms.
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SYNGAP1-related non-syndromic disorder (SYNGAP1-related disorder) is a rare genetic condition where patients have developmental delay and often suffer from severe epilepsy, intellectual disability, autism, ataxia, apraxia, and sleep disorders for their duration of their lives.
De novo mutations in a single copy of the human SYNGAP1 gene cause SYNGAP1-related disorder. The SYNGAP1 gene encodes the information needed by neurons to produce the SynGAP1 protein. In the brain, the SynGAP1 protein functions as a key player for normal brain development and neuron-to-neuron communication. In people with SYNGAP1-related disorder, the mutations in SYNGAP1 lower the overall amount of SynGAP1 that can be produced. In turn, this limits the availability of SynGAP1 to carry out its important functions in brain development and cellular communication.
It’s thought that 1 in every 16,000 people have SYNGAP1-related disorder, representing ~1-2% of all non-syndromic intellectual disability cases. There is no known cure and no effective treatments to help those afflicted with this rare disorder.
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GRIN disorder belongs to a large family of rare neurological disorders where patients present with developmental delay, intellectual disability, autism, speech deficiency, inability to walk, gastrointestinal issues, visual impairment, and epilepsy.
GRIN disorder is caused when de novo mutations occur on one of the seven genes that encode for subunits of the ionotropic glutamate receptor, the NMDA receptor. NMDA receptors are made up of two types of proteins: GluN1 proteins, which are encoded by the GRIN1 gene and GluN2 proteins, which are encoded by the GRIN2A, GRIN2B, or GRIN2D genes. When disease causing mutations occur in any of these subunit encoding genes, the function of the entire NMDA receptor is impaired in the brain.
It is predicted that GRIN disorder impacts 1 in every 5,208 people and there are no FDA-approved treatments of GRIN disorders.
Data from: NCBI, Fraxa, Syngap Research Fund, Brain, cureGRIN
Approach
Once we have identified the biological mechanisms of a disorder, we correct them with innovative treatments, with clinical endpoints informed by patients.
Select neurological disorders with a defined genetic population
Carry out research to identify different impaired cellular mechanisms of the disorder
Develop treatments that distinctly rescue each biological impairment
Run clinical trials with endpoints most meaningful to patients and their families
Advantages
By correcting multiple biological mechanisms implicated in each disorder, we hope to increase treatment efficacy and tolerability to improve the lives of patients with rare neurological disorders.
Improve treatment effectiveness by treating the biological causes not just symptoms
Improve treatment effectiveness by combining treatments to target multiple pathologies
Reduce the length and cost of clinical trials by repurposing on-the-market therapeutics
Leadership
Nospharma was founded by scientists with a deep understanding of the role biological mechanisms play in behavioural neuroscience and neurophysiology.