Synapse-restoring pill set for human trials as novel schizophrenia treatment

Spinogenix, the company behind the once-a-day pill that restored lost nerve cell connections in people with amyotrophic lateral sclerosis (ALS), has now set its sights on using the pill to provide a novel treatment for another debilitating disease: schizophrenia.

Earlier this year, New Atlas reported on a groundbreaking once-a-day pill that restored lost nerve cell connections or synapses in the brain. The creation of biopharmaceutical company Spinogenix Inc., early clinical trials of the drug, called SPG302, to treat the fatal nervous system disease amyotrophic lateral sclerosis (ALS) yielded impressive results.

Now, Spinogenix is again about to embark on a clinical trial of SPG302, this time to evaluate its effectiveness in treating another serious and debilitating disease: schizophrenia.

“We are excited to advance the first clinical therapy capable of reversing synapse loss in schizophrenia, which may provide a much-needed advancement in the treatment of multiple symptoms and patients who are treatment resistant,” said Dr. Stella Sarraf, Spinogenix’s CEO and founder.

Schizophrenia is a serious, chronic mental illness that affects how people think, feel, and perceive. Its hallmark is psychosis, which describes when a person is disconnected from reality. Schizophrenia also presents with ‘positive symptoms’ like hallucinations, delusions, and disorganized speech, ‘negative symptoms’ like social withdrawal, an inability to feel pleasure (anhedonia), apathy, and lack of emotions, and cognitive symptoms such as problems with memory, attention and reasoning.

Increased dopamine activity in parts of the brain can contribute to positive symptoms. In contrast, reduced dopamine activity in other parts may affect negative and cognitive symptoms. While antipsychotic medications that block dopamine receptors can reduce the symptoms of psychosis, they don’t cure it. And, for some, antipsychotics don’t work at all.

“Antipsychotics targeting dopamine signaling have been used since the 1950s to control positive symptoms, but leave psychosis inadequately controlled in many patients and have little benefit on negative and cognitive symptoms,” Sarraf explained. “As demonstrated by the expected entry of promising emerging antipsychotics into the schizophrenia treatment landscape, we are at an inflection point where new targets and novel approaches like SPG302 represent our best option to show meaningful improvements for this population.”

Billed as a regenerative treatment, SPG302 has the unique ability to restore crucial synapses, the connections through which nerve cells – neurons – communicate. Previous studies have suggested that schizophrenia is associated with a loss of glutaminergic synapses, the main excitatory synapses in the brain that use the amino acid glutamate as a neurotransmitter. (Signals sent across excitatory synapses increase the activity of the receiving neuron; signals sent across inhibitory synapses reduce it.) Through its method of action, SPG302 rapidly regenerates glutaminergic synapses. It’s a completely new approach.

“The synaptic regenerative approach being championed by Spinogenix may add an important new option to the armamentarium of drugs available to those battling schizophrenia,” said Dr. Merv Turner, a member of the Spinogenix board of directors. “While long believed to be of potential benefit, targeting synapse loss in practice represents an entirely new therapeutic strategy. SPG302 has the potential to become another novel and high-value addition to the schizophrenia therapeutics space.”

Having been granted approval from the Australia Human Research Ethics Committee (HREC), Spinogenix is actively enrolling participants for its Phase 2 clinical trial to evaluate the safety, effectiveness, tolerability and pharmacodynamics of once-a-day SPG302 as a treatment for schizophrenia.

Source: Spinogenix