Parkinson’s disease is a neurodegenerative disorder and belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine-producing brain cells. The four primary symptoms of PD are tremor, or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance and coordination. Patients may have difficulty walking, talking, or completing other simple tasks.
However, current approved therapies treat only the symptoms of Parkinson’s disease. MANF, a neurotrophic factor indicated for the treatment of Parkinson’s, offers the promise of safely and effectively protecting dopamine producing neurons from death and rejuvenating dying cells to ultimately stop the progress of the disease and restore normal function to patients. This line of research is being conducted by New York-based Amarantus Biosciences, which is headed by Gerald Commissiong.
Prior to becoming president and CEO in October 2011, Commissiong was the company’s chief operating officer. Before co-founding Amarantus, Commissiong played professional football for the Calgary Stampeders of the Canadian Football League. Commissiong received a B.Sc. in Management Science and Engineering with a focus on Financial Decisions from Stanford University. Commissiong’s father is Dr. John Commissiong, who discovered the MANF protein; father and son have been working together since 2007.
As part of a new series on Parkinson’s and new approaches to developing effective therapies for this major unmet medical need, WuXi AppTec Communications recently interviewed Commissiong about the cutting-edge research his company and the industry is doing to find a cure for this debilitating disease.
WuXi: How would you describe the progress being made in finding new approaches for developing drugs to treat neurological disorders, including Parkinson’s disease?
Gerald Commissiong: I think emerging concepts that have given rise to new cancer therapies are changing the way scientists look at biology in general. What’s becoming clear is that the one compound, one target approach has reached some of its limits in terms of how it can positively impact complex medical conditions and new paradigms are being thought of in terms of systems approaches. With that in mind, complementary approaches to biology are being combined into advanced therapy development for several neurological disorders, including Parkinson’s disease.
WuXi: What are researchers learning about the causes of Parkinson’s disease and are there implications for other neurological disorders? Is the NIH’s Brain Initiative helping your research efforts?
Gerald Commissiong: I think some important biological characterizations of the brain are being advanced by the NIH’s Brain Initiative. We are learning about the some of the single cell activity at the dopaminergic cell level, and the subtypes thereof that is having an impact on how we approach PD. We have certainly been helped with publicly available data on our MANF (mesencephalic-astrocyte-derived neurotrophic factor) protein in helping us consider indication selection and how we could potentially approach PD in the clinic.
WuXi: Is Parkinson’s disease caused by genetic abnormalities, environmental factors or a combination of the two?
Gerald Commissiong: It is often said that genetics load the gun, with the environment pulling the trigger. It certainly seems this likely holds true in Parkinson’s, with different combinations of genetics increasing or decreasing risks, and certain lifestyle activities, such as smoking, which decreases Parkinson’s risk. The interplay of these statistical realities is important in furthering researching the roots cause(s) of Parkinson’s.
WuXi: What scientific breakthroughs are needed to better understand the causes and progression of Parkinson’s?
Gerald Commissiong: Reliable biomarkers that allow us to study pre-symptomatic patients are critical to expanding our understanding in this field because we will be able to start trying experimental treatments on patients that have enough neurons left to make a significant regenerative impact.
WuXi: What are the major challenges in treating Parkinson’s disease?
Gerald Commissiong: The major issue I see is that therapies with the most promise are being tested on patients least likely to respond at the later stages that have suffered loss of virtually all of their dopaminergic neurons. This is one of the things we have to work on in the design of clinical studies where we start to treat patients with experimental regenerative therapies earlier in the disease process.
WuXi: What is your company’s technology and how are you applying it?
Gerald Commissiong: We discovered and are developing the endogenous neurotrophic factor Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) for the treatment of Parkinson’s disease and ophthalmology. MANF is an endoplasmic reticulum stress response protein that has very specific activity in regenerating dopaminergic neurons leading to cellular recovery, synaptogenesis and normalization of dopamine levels in animal models of Parkinson’s disease. We are developing the therapy to be delivered into the substantia nigra and striatum in the brain’s basal ganglia network, which is the network in the brain that heavily involved in controlling movement.
WuXi: How does your company’s approach differ from others in this field?
Gerald Commissiong: Most companies are developing ways to extend the life of levodopa therapy. We seek to regenerate the utility of the dying dopaminergic neurons to return normal functions to the basal ganglia network.
WuXi: How will Parkinson’s disease treatments evolve over the next five years? Is a cure possible?
Gerald Commissiong: I think the potential technologies that could lead to major advancements are already available, and it will be a matter of understanding how well they can work together to lead to disease modification. We believe this is a process that should be accelerated and are hopeful clinical successes with boost investment in the space. We believe a functional cure for patients is potentially within reach.