Spinogenix is developing a new way to treat neurodegenerative diseases and other conditions that are characterized by the degeneration of synaptic connections between neurons. To date, most efforts to develop new treatments for these conditions have focused on slowing disease progression. At Spinogenix, we believe that slowing progression is not enough. Our approach is very unique. We are developing a platform of novel small molecule drugs that have the remarkable property of being able to regenerate synapses. This “regenerative medicine” approach can potentially benefit people with dementia, movement disorders, neuropsychiatric conditions and other diseases.

Synapses are connections between neurons through which signals flow from one neuron to another. As such, synapses are a fundamental and indispensable physical basis for neural communication, enabling cognition, movement, perception, memory and other faculties of mind. Deterioration of synapses is an early and progressive feature of a broad spectrum of neurodegenerative, neuropsychiatric and other diseases collectively known as the “synaptopathies”. For any therapy to have a chance at reversing the symptoms of these diseases it must promote the regeneration of synapses.

The synaptopathies comprise a large and etiologically diverse set of conditions, including well known diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and schizophrenia. A subset of synaptopathies spanning neurodegenerative diseases, neuropsychiatric conditions, and neurodevelopmental disorders, as well as injury and aging:

There are no approved therapies that regenerate synapses to restore cognitive, motor and other functions in any of these diseases. Spinogenix is positioned as a leader in this space with its first-in-class synaptic regenerative small molecules, the SPGs.

The SPGs have a very unique set of properties that we termed TAGS™, which stands for Transient Activators of Glutamatergic Synaptogenesis. SPGs trigger the formation of new synapses that use the amino acid glutamate as a neurotransmitter. Such synapses are the most common type of “excitatory” synapses (meaning that they stimulate the receiving neuron), and they are preferentially lost in
neurodegenerative diseases. SPGs work by regenerating dendritic spines, the specialized small protrusions of neural membrane that comprise the postsynaptic element at ~90% of glutamatergic synapses:


The synaptogenic effect of SPGs as seen by labeling of dendritic spines. Images are from apical dendrites in the CA1 field of hippocampus in drug naïve (left) and drug treated (right) animals.

The regenerative activity of SPGs is remarkably well suited to treat synaptopathies. Some of the key features of their activity are as follows:

Rapid Acting – SPGs induce the formation of new, functional dendritic spine synapses within 4 hours or less in vitro, while synaptic and behavioral benefits are evident in vivo within weeks during daily treatment.

Sufficient Transient Exposure – Synaptic regeneration and behavioral benefits in cognitive and motor symptoms in animal models (ALS, Alzheimer’s, spinal cord injury, traumatic brain injury) are achieved with daily dosing of SPGs that have a relatively short half-life.

Self-perpetuating and Self-limiting – SPGs activate a process that carries forward on its own to generate physiologically relevant numbers and shapes of dendritic spine synapses. Treatment with higher doses than necessary, or for longer periods, does not alter this activity profile.

Durable Effects – New synapses induced by SPGs can last weeks or more after cessation of drug treatment.

Many of the new therapies being developed for neurodegenerative diseases such as ALS and Alzheimer’s disease are large macromolecules called “biologics”. Such therapies, which include antibodies that bind to toxic proteins or oligonucleotides that suppress the expression of a disease-related gene product, are often difficult to administer and costly to produce at scale. By contrast, SPG302 is intended to be used as a once-a-day pill, which makes drug administration and compliance simple, and significantly reduces cost. Altogether, SPG302 may provide a simple and cost effective, yet powerful approach to treating the synaptopathies. This approach has the potential to be used alone as a “monotherapy” or as a regenerative component to combination therapies that include treatments targeting specific disease processes.