With IND approval, the therapeutics have become the first LBPs for Parkinson’s disease cleared by the FDA.
United Kingdom-based 4D pharma has received clearance from the U.S. Food and Drug Administration for its Investigational New Drug (IND) applications for therapeutics MRx0005 and MRx0029 intended for the treatment of Parkinson’s disease. The company specializes in the development of Live Biotherapeutic products (LBPs), which are derived from the microbiome.
Parkinson’s disease is a progressive neurodegenerative disorder caused by the loss of dopamine-producing neurons in the brain, leading to symptoms such as tremor, stiffness, slowed movement, and impaired balance and coordination. More recently, research has found that gastrointestinal symptoms, such as constipation and alterations of the enteric nervous system, a mesh-like system of neurons that innervate the gastrointestinal tract.
Studies of Parkinson’s disease have been homing in on the gut microbiome, a term for the trillions of microorganisms and their genetic material that live in intestinal tracts involved in functions critical to health and well-being. Researchers have uncovered that in patients with Parkinson’s disease, there is a dysbiosis of the gut microbiome, meaning that there is a loss of beneficial microbial input or an expansion of pathogenic microbes. Because the gut and the brain share an axis and communicate with one another, this dysbiosis could be a potential driver of the pathogenesis of the disease.
Now, 4D pharma is utilizing the gut-brain axis to develop novel treatments for those with the disease. MRx0005 and MRx0029 are single strains of gut commensal bacteria that have been derived and isolated from healthy human donors. The bacteria are then grown from cell banks and encapsulated for oral administration and selective delivery to the gut.
In pre-clinical studies of the therapeutics, both showed a reduction in neuroinflammation and protected neurons from oxidative stress-induced death and improved gut barrier integrity. MRx0005 and MRx0029 respectively protected against the loss of dopamine metabolites and dopamine-producing neurons in the brain in animal models of Parkinson’s disease. MRx0029 specifically has been shown to improve intestinal epithelial integrity, which protects intestinal permeability, while MRx0005 has been shown to upregulate expression of neuroactive molecules and their receptors in vivo and protect against loss of dopamine metabolites which induces Parkinson’s disease.
“Current treatments focus on symptoms but do not address the underlying causes of neurodegeneration. Patients and clinicians are in need of new, more effective treatment options, and the gut-brain axis is an exciting area of innovation with the potential to change the way we approach Parkinson’s treatment. We believe that our LBPs MRx0005 and MRx0029, which each have different mechanisms of action worthy of investigation, provide a unique opportunity to address the high unmet needs of those living with Parkinson’s disease,” said 4D Pharma Chief Scientific Officer Dr. Alex Stevenson.
With IND approval, the therapeutics have become the first LBPs for Parkinson’s disease cleared by the FDA. Now, 4D pharma anticipates initiating a Phase I clinical trial in mid-2022. The multi-center, randomized, double-blind, placebo-controlled study will evaluate the safety and tolerability of both MRx0005 and MRx0029 in separate cohorts of patients with Parkinson’s disease. Researchers will also measure biomarkers relating to the mechanisms of action in the therapeutics.
4D pharma has teamed up with Parkinson’s U.K., a non-profit organization focused on education and improving treatments for patients. In collaboration, the companies have established a Patient Advisory Board comprised of people living with Parkinson’s disease. Patients will help provide valuable insight into living with the condition to 4D pharma and contribute to raising awareness of the issues people with Parkinson’s face with current treatment options.
