FDA Accepts INDs for Parkinson Disease Treatments MRx0005 and MRx0029

Meglio,Marco;

FDA Accepts INDs for Parkinson Disease Treatments MRx0005 and MRx0029

March 2, 2022

Marco Meglio

Publication

Article

NeurologyLiveApril 2022

Volume 5

Issue 2

The two investigational agents from 4D Pharma have both been shown in preclinical studies to reduce neuroinflammation and to protect neurons from oxidative stress-induced death.

Peter LeWitt, MD

According to an announcement, the FDA has cleared the investigational new drug (IND) applications for 4D Pharma’s live biotherapeutic, gut-derived Parkinson disease (PD) agents MRx0005 (Parabacteroides distasonis) and MRx0029 (Megasphaera massiliensis), which will be initiated in a first-in-human phase 1 study beginning in mid-2022.¹

In preclinical settings, these oral, single-strain medicines discovered using 4D Pharma’s MicroRx platform have both shown the ability to reduce inflammation, including inflammation induced by α-synuclein, and to protect neurons from oxidative stress-induced death. In addition to demonstrating positive impact on PD pathology, MRx0005 and MRx0029 have respectively protected against the loss of dopamine metabolites and dopamine-producing neurons in the brain in animal models of Parkinsonian syndrome.

"Entering the clinic with our novel CNS programs stemming from our proprietary MicroRx platform will represent an important step for 4D pharma’s continued growth and leadership in the microbiome field. We believe MRx0005 and MRx0029 are the first ever Live Biotherapeutic products for Parkinson’s to enter the clinic," Alex Stevenson, chief scientific officer, 4D Pharma, said in a statement. "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 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 disease," Stevenson added.

The new phase 1 study will be a multicenter, randomized, double-blind study with an active placebo group to assess the safety and tolerability of MRx0005 or MRx0029 in separate cohorts of patients with PD. Investigators will also evaluate biomarkers related to the mechanisms of action of the candidates.

To date, MRx0005 has been shown to upregulate expression of neuroactive molecules and their receptors in vivo and protect against loss of dopamine metabolites in the brains of mice with induced parkinsonian syndrome. As for MRx0029, the therapeutic has demonstrated an ability to improve intestinal epithelial integrity, which is related to intestinal barrier function and intestinal permeability, symptoms that have been thought to contribute to the onset or progression of PD. Additionally, MRx0029 also has been shown to induce the differentiation of dopaminergic neuronal phenotype in vitro, and in an animal model of PD protected against the loss of dopaminergic neurons.^1,2

"Parkinson disease is a devastating condition impacting more than 10 million people globally. As the global population ages, this number will continue to increase. There is growing evidence suggesting that the gut-brain axis could be key to developing new treatments for several neurological disorders, particularly Parkinson disease," Peter LeWitt, MD, Sastry Foundation Endowed Chair in Neurology, Wayne State University School of Medicine, and coordinating investigator of the phase 1 trial, said in a statement. "Oral, gut-targeted treatments such as 4D pharma’s Live Biotherapeutics MRx0005 and MRx0029 offer an exciting new way for possibly slowing Parkinson’s disease progression. The development of these potential new therapies is really breaking new ground in the field."

4D Pharma has also collaborated with Parkinson’s UK, a nonprofit organization, to establish a Patient Advisory Board comprised of people living with PD. This board provides a patient-centric perspective to 4D Pharma and will continue to focus to raising awareness of the issues these patients may face with their current treatment options.