“ dysregulated in Parkinson’s disease and LID, Dr. Mouradian’s group decided to concentrate on pharmacological approaches to modulate the opioid system. Based on their knowledge L-dopa-Induced Dyskinesia about two different opioid receptor subtypes that contribute to the manifestation of LID in opposing ways, they focused on Creates a Huge Unmet Need simultaneously blocking μ (mu) opioid receptors and stimulaany people mistake the involuntary movements of ting κ (kappa) opioid receptors to provide the greatest benefit people with Parkinson’s as a symptom of the disease,” and the fewest negative consequences. says Dr. Mouradian. “You can see an example of these “Putting two and two together,” Dr. Mouradian says, “we movements in footage of Michael J. Fox, who appears to be realized that the analgesic drug nalbuphine has these same dual fidgeting as he speaks. But the movements, known as L-dopaactions.” Often used for perioperative pain management and induced dyskinesia (LID), are actually an adverse effect of labor pain, nalbuphine has a known safety profile and is apyears of treatment with L-dopa.” proved by the U.S. Food and Drug AdminIntroduced for human use in 1969, L-dopa istration (FDA). “Research advances much remains the gold standard drug for treating more quickly when you are able to start out the motor symptoms of Parkinson’s disease, with a drug that is already proven to be safe are an important part of including bradykinesia (slow movement), in humans,” says Dr. Mouradian, who rethe translational tremor, and rigidity. “Without L-dopa,” adds ceived a grant from the Michael J. Fox Dr. Mouradian, “patients with advanced Foundation for Parkinson’s Research to beresearch process,” Parkinson’s disease would have difficulty movgin research on repurposing nalbuphine to says Dr. Mouradian. ing and attending to their daily activities.” alleviate LID. Symptoms of Parkinson’s disease result Subsequently, Dr. Mouradian cofounded “Discoveries with national from depletion of the neurotransmitter dopaMentiNova Inc., a start-up biotechnology and international mine in a part of the brain called the striacompany dedicated to finding a treatment patent protection are tum, interrupting communication between for LID. She serves as the company’s presithe cells. Administration of L-dopa restores dent and oversees its scientific and clinical more likely to attract the production of dopamine; communication development efforts. investors. And when you between nerve synapses resumes, and sympShe was supported by an investment from toms are alleviated. But not forever. Foundation Venture Capital Group (FVCG), have partners, you have L-dopa-induced dyskinesia is caused by an affiliate of the New Jersey Health a better chance to dysregulation of genes, proteins, and neuroFoundation (NSHF), which makes private transmitter systems and their receptors in the investments in life science start-up compaaccelerate the pace of striatum. Dr. Mouradian compares this nies headed toward commercialization. translating scientific process to a perfect storm. Signs of LID Though independent of Rutgers, The State knowledge for the generally begin after four to six years of University of New Jersey, both groups work treatment, resulting from long-term L-dopa closely with Rutgers, including its Office of good of public health.” administration along with ongoing neuroResearch Commercialization, to provide scidegeneration that leads to further dysregulaentists with strategic support in areas tion of striatal systems. This creates a vexing challenge: how including financing, licensing, intellectual properties, and the to prevent LID while continuing to provide patients with the securing of patents. benefits of L-dopa. “We were attracted by the opportunity to invest in this research because it appeared to have promising results,” says Focusing on Nalbuphine George F. Heinrich, MD, vice chair and CEO, FVCG. “Since hile deep brain stimulation is an option for some the drug already had FDA approval for another indication, patients with LID, it is an invasive procedure and we anticipated a faster IND [Investigational New Drug] filing carries risks. and clinical trial process testing the efficacy of the treatment. Knowing that opioid transmission is one of the systems “Dr. Mouradian is an international expert, very involved, productive for a few more years would be a tremendous gain,” she says. M “Patents W Robert Wood Johnson I MEDICINE 11