Researchers at the University of California, Irvine (UCI) are working toward developing tissue-engineered therapeutics for the temporomandibular joint (TMJ) using patient-centric approaches. Fourth-year Ph.D. candidate Ryan Donahue, under the tutelage of Dr. Kyriacos A. Athanasiou, has been working toward this goal by publishing scientific articles and participating in the NSF Innovation Corps (I-Corps) program at UCI.
“The I-Corps program is a market discovery program that leads innovators through a learning process to discover their place in the market. Central to any medical therapeutic is the patient receiving such a therapeutic and the doctor delivering it. Through this program, we collaborated with The TMJ Association to talk with patients to learn and understand the current needs directly from patients,” said Mr. Donahue.
Mr. Donahue and his team interviewed patients from a wide array of backgrounds and types of temporomandibular disorders (TMDs). The program focused on digging into the patient needs by doing personal, individualized interviews. “Typically, we are the ones doing the benchtop science, but it is really rewarding to learn what the clinical needs are from a patient perspective and experience. We were able to get the patient viewpoint about the debilitating pain and lack of function so many TMJ patients experience,” said Mr. Donahue.
This was a unique collaboration because the benchtop scientists rarely interact with patients. As the UCI-based team continues to translate potential TMJ therapeutics, they want to develop scientifically sound, patient-centric approaches. “One of the biggest previously-held notions and commonalities of all TMJ patients that we confirmed from the patient interviews is they want to avoid additional end-stage, alteration surgeries, such as total joint replacements. The patients are keenly aware that the outcomes are not consistent and that each doctor they see might offer a different treatment,” said Mr. Donahue. This creates chaos for patients that are just trying to get pain relief or improved jaw function – they do not know where to go or what to do. “Moving forward, it will be important to take these considerations into account by developing approaches that are minimally invasive, if possible, and that are grounded in evidence by testing in animal models prior to use in clinical trials and widespread use in humans. By doing so, this will hopefully lead to more consistent clinical outcomes and create less confusion for doctors and patients alike moving forward.”
However, developing these therapeutics is easier said than done according to Dr. Athanasiou. “The TMJ field significantly lags behind that of other joints, such as the knee. Indeed, the science and understanding of the temporomandibular joint continue to be lacking in comparison to the knee. As a result, TMJ treatments are also lacking.”
The UCI group recently published an article titled, “Knee orthopedics as a template for the temporomandibular joint” in Cell Reports Medicine that compares the oral and maxillofacial field to that of orthopaedics and how the TMJ field might use orthopaedics as a template to propel itself forward in understanding and concomitant treatment modalities. Corresponding author, Dr. Athanasiou, describes the content of the paper: “In this paper, we describe and analyze the differences between the two fields. The knee orthopaedics field is well-developed; it has higher research output, clear treatment algorithms, and an abundance of tissue-engineered products when compared to the TMJ.”
“By using the orthopaedic field as a template, we call for driving the basic and translational research and implementing more clinical products for the TMJ,” says Mr. Donahue, one of three co-first authors and ten total authors from a variety of institutions in the United States. “We discuss the joint disease progression, clinical treatments, and commercial products for each joint and focus on how we can break the vicious cycle that forcibly drags the TMJ field down.”
In the Cell Reports Medicine paper, the authors describe this vicious cycle that leaves 36 million people living with TMDs. Mr. Donahue and his co-authors discuss how a lack of TMJ research output and funding leads to no clinical trials, which means there is a lack of products to use for TMDs. This results in no commercial success and causes little to no funding from funding agencies and guidance from regulatory agencies. This provides no precedent for translational TMJ research and feeds back into the loop leading to a lack of TMJ research. However, by using orthopaedics as a model, the TMJ field can hopefully reach for a higher level.
“We talk about increasing TMJ research quantity, bolstering training for researchers and clinicians, specifying and narrowing indications to establish a commercial landscape, and implementing regulatory guidance for the TMJ in the future. Going about each of these tasks, the knee orthopaedics field has existing mechanisms in place that ensure improved clinical outcomes, and these mechanisms can be used as a template for the TMJ moving forward,” says Mr. Donahue.
The National Academy of Medicine report on TMJ states, “Action is urgently needed to improve care for individuals with a TMD.” To this end, Mr. Donahue, Dr. Athanasiou, and the rest of the UCI-based team are working diligently to develop patient-centric approaches that are grounded in evidence for treating TMDs. However, they note that this is just the beginning of a long road ahead. “When you look at the classical example of pharmaceutical companies bringing a new drug to market, that takes up to 10 to 15 years in many cases. Here, we have to climb an even larger mountain prior to getting a tissue-engineered therapeutic approved since there is nothing like it out there for the TMJ currently,” says Dr. Athanasiou.
Collaboration with The TMJ Association added valuable patient viewpoints and insights for the UCI-based group. Mr. Donahue said, “Going forward, it is imperative that any groups developing potential therapeutics interact with patients and advocacy groups such as The TMJ Association and understand the human aspect and morbidity that comes with TMDs.” As researchers continue to move forward with developing cutting-edge therapeutics, The TMJ Association advocates for including the experiences and expectations directly from the patients in basic and clinical research, and treatment development in this area − for they are the experts.