By Aditya Tummala, Sydney Wiredu, Derek Liu, and Pranav Ramesh
Harvard College, Class of 2026
Long-time researchers in the field of rare diseases know what it’s like to experience a lack of adequate funding, the logistical challenges of small patient populations, and the sometimes-daunting isolation of working in a field where there is limited expertise. But we are here to tell you that there has never been a more exciting time to get involved in rare disease research, thanks to programs that are overcoming barriers to innovation and engaging a new generation of scientists and thinkers.
We are a team of Harvard undergraduates who participated in last year’s Harvard Rare Disease Hackathon, sponsored by the National Organization for Rare Disorders (NORD). This hybrid event allowed students from around the country to collaborate, test, and pitch technology-based solutions to today’s rare disease challenges. The Hackathon is taking place again this year, on March 1-2, 2025, and we encourage anyone in the U.S. who is interested to learn more and sign up here. (Merit- and need-based scholarships are available to those who apply by February 12 at midnight.)
Read on to learn about our award-winning project, other exciting innovations that are bringing hope to rare disease researchers, and the programs NORD offers to help young and emerging researchers enter the field in a meaningful way.
Fostering Rare Disease Innovation
For decades, NORD has been instrumental in breaking down barriers to entry for researchers and innovators. The organization provides crucial funding through research grants and fellowships, supporting both established researchers and emerging talent in the field. Additionally, NORD plays a vital role in helping innovators navigate the complex regulatory environment surrounding rare disease treatments. By offering guidance on regulatory pathways and facilitating interactions between researchers, pharmaceutical companies, patient organizations, and regulatory bodies like the U.S. Food and Drug Administration (FDA), NORD helps accelerate the development and approval of new therapies.
NORD’s commitment to fostering innovation extends beyond traditional medical research. The organization places a strong emphasis on education, awareness, and ethical considerations in rare disease research and treatment. Through conferences like the NORD Breakthrough Summit, webinars, and educational materials, NORD disseminates knowledge about rare diseases to healthcare professionals, researchers, and the general public. NORD’s advocacy for ethical research practices ensures that innovations in the field prioritize patient well-being and adhere to the highest standards of scientific integrity. By creating a collaborative ecosystem that spans patients, researchers, healthcare providers, and policymakers, NORD has cultivated an environment where creative solutions can flourish, demonstrating that impactful contributions to rare disease patient health and well-being can come from diverse sources and perspectives.
The Harvard Rare Disease Hackathon
One place to witness this collaboration and creativity in action is at the Harvard Rare Disease Hackathon, sponsored by NORD. Our team won “Most Novel Solution” at last year’s Hackathon for our medical device model for Charcot Marie Tooth Disease: the CMT4J pressure-reducing customizable boot.
Charcot Marie Tooth Type 4J is a rare and severe disease that presents similarly to ALS, with high levels of misdiagnosis. Often, progressive physiological defects such as an arched food and weakened ankle permanently disable people with CMT disease. Unfortunately, these challenges lack affordable or accessible therapeutic solutions barring substantial, seldom effective, surgical intervention. Leg braces can help mitigate pain and slow down symptoms, but significant phenotypic variations in the manifestation of deformities require a custom brace to be designed for each individual. To meet this challenge, we proposed a customizable brace (see Figure 1) powered with an AI app allowing for adjustment recommendations, analogous to dental aligners, for preventing muscular dystrophy specifically in patients with all forms of CMT and other foot and lower leg deformities.
We constructed a three-pronged approach of utilities as part of our solution: The physical surface model, an AI-powered app to generate continuous brace adjustments, and the customizable boot itself.
A weekly progress monitoring system was developed, creating a 3D representation of the patient’s foot geometry for generating adjustment recommendations. Weekly, patients will be instructed to stand barefoot within a pin-art-inspired mold box, placing their full weight on a gridded film placed over it. The pins will press against the film, creating indentations that correspond to the pressure exerted on each point of the foot’s surface. Following the imprinting process, the participant will remove the film from the mold, scanning the density map created on the film. This will capture the precise variations in the film’s surface caused by the pin indentations, generating a digital representation of the foot’s three-dimensional morphology from the two-dimensional film (see Figure 2).
This scan will then be sent to the app, utilizing the Hough Transform algorithm within the OpenCV library to identify and isolate the individual dots present in the image. This algorithm is specifically designed to detect circular shapes in an image, making it ideal for accurately identifying the grid points in the film, even in cases of slight warping or distortion. A pre-trained Deep Q-learning model will translate the generated heatmap data into boot pressure adjustment commands. Deep Q-learning with asynchronous off-policy updates is a reinforcement learning technique well-suited for robotic manipulation due to its ability to learn optimal actions through trial and error within a simulated environment. In this case, the model will be trained using simulated foot pressure data to learn the optimal sequence of pressure adjustments within the customizable brace that minimizes localized pressure and discomfort on the foot. These recommendations will be translated into specific adjustments that each patient can make at home on their boot, analogous to present-day remote monitoring of dental aligners.
Addressing each of the points of dystrophy faced by those with CMT, our boot incorporates artificial peroneus brevis and tibialis posterior muscles, providing targeted pressure to restore proper ankle alignment and stability. Additionally, an artificial tibialis anterior muscle and Achilles tendon will be strategically positioned to prevent the development of a high arch and foot drop, while allowing for a more natural and fluid gait. The addition of these adjustable components to existing designs ensures the boot will effectively reduce ankle instability and arch deformities while minimizing pressure points and enhancing overall comfort.
The current CMT solutions in the market are not only inaccessible, they are unaffordable. Due to the progressive worsening of this disorder, physicians are left with no choice but to resort to invasive, expensive, and technically challenging surgery to alleviate the burden and maintain patients’ ability to walk. To prevent the need for these drastic solutions, we proposed this multi-faceted approach—at the crossroads of biomedical physiology, engineering, mathematics, artificial intelligence, and economics—to show how potentially simple, accessible solutions such as the CMT boot can be created.
The Harvard Rare Disease Hackathon sponsored by NORD provided us with the opportunity to think critically, collaborate with peers from diverse backgrounds, and provide hope for new innovation to a disease that, to date, has no cure and few supportive therapies. The event demonstrates how cultivating an environment of cross-field innovation can be integral in the fight for rare disease innovation.
More Novel Approaches to Diagnosis, Treatment, and Care
Our solution is just one of many being explored right now in the field of rare diseases. Recent advances in rare disease research highlight a range of innovative approaches that are transforming the landscape. One notable success story is the Stanford Rare Disease AI Hackathon, which brought together interdisciplinary teams to tackle rare disease challenges using artificial intelligence (AI). Similarly, RareNeu, the Northeastern Rare Disease Chapter, exemplifies the power of community-driven initiatives in advancing research. Another significant development is the Chan Zuckerberg Initiative’s funding of projects like the Rare As One Project, which aims to enhance research infrastructure and foster collaborations among rare disease researchers. These success stories underscore how focused, collaborative efforts can accelerate progress in rare disease research.
Interdisciplinary approaches are crucial for driving innovation in this field. The integration of bioinformatics with traditional research methodologies has opened new avenues for understanding rare diseases. Platforms like UPWARD (Uniting People Working Against Rare Diseases) on GitHub provide a collaborative space for researchers to analyze meta-information databases and share insights and resources. Additionally, the HL7 FHIR standard has revolutionized data sharing by providing a modular framework for secure healthcare data exchange. This standard supports diverse applications, including mobile apps and electronic health records (EHRs), thereby enhancing the ability to gather and utilize patient data effectively.
The role of technology, particularly AI, is increasingly pivotal in rare disease research. AI tools are transforming both diagnosis and treatment by analyzing complex datasets such as imaging and genetic information. Advanced algorithms, including supervised and unsupervised learning models, can detect patterns and predict diagnoses with unprecedented accuracy. In treatment, AI techniques like neural networks reveal novel patterns in drug interactions and optimize clinical trials by improving patient recruitment, trial design, and predictive analytics. These technological advancements not only enhance diagnostic precision but also streamline the development of effective treatments, marking a significant leap forward in addressing the challenges associated with rare diseases.
With all these advancements and more on the horizon, there is no shortage of possible pathways to make a real difference during your career as a rare disease researcher.
Taking the First Step
Organizations like NORD not only provide a centralized hub for research and innovation but also spark enthusiasm and creativity in the world of rare disease innovation, particularly in youth populations. NORD’s Students for Rare program enables student volunteers from high school through medical school to spread awareness, contribute to curricula, connect with future employers in the medical research field, and raise funding for rare disease innovation. Programs like this are fostering a new generation of innovators who are passionate about making a difference.
By working together with experienced researchers, youth can leverage their complementary strengths to accelerate drug discovery and improve patient outcomes. To ensure the success of youth-led initiatives, it is essential to provide mentorship, guidance, and adequate resources for young researchers. Educational programs, online platforms, and competitive grants are all tools that can help reach more young people and get them involved as future innovators.
Looking ahead, it is crucial to recognize that innovation in rare diseases must be approached from multiple angles. Breakthroughs can manifest in various forms—from groundbreaking scientific discoveries to novel patient support systems, creative fundraising methods, or simply well-meaning students seeking to make an impact. This multi-faceted approach is essential because rare diseases present unique challenges that often require unconventional solutions.
As we’ve seen through NORD’s initiatives, the potential for meaningful contribution exists for everyone, regardless of their background or expertise. Whether you’re a researcher, a patient, a caregiver, or simply someone with a creative idea, your perspective could be the key to unlocking new possibilities in rare disease care and treatment. We encourage all readers—no matter their age, expertise, or experience—to start thinking critically about the problems they see around them. Anyone can make a difference, just be curious! Together, we can shape a future where no patient is left behind.
Works Cited:
Bird, T. D. (2017). Charcot-Marie-Tooth neuropathy type 1. GeneReviews. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817837/
Cure CMT4J Foundation. (n.d.). Charcot-Marie-Tooth Type 4J (CMT4J). Retrieved August 30, 2024, from https://www.curecmt4j.org/cmt4j/
Kuan, P.-F., Wasthage, T., Smith, K., Urrutia, E., Chiavacci, R., Kopechek, J., … & Wojcik, G. L. (2021). A framework for evaluating differential expression analysis methods in multi-condition RNA-Seq experiments. Frontiers in Genetics, 12, 602292. https://doi.org/10.3389/fgene.2021.602292
[Charcot-Marie-Tooth Disease (CMT) Overview]. (2021, May 7). YouTube. https://www.youtube.com/watch?v=PB_qko3KkCwNCBI Hackathons. (n.d.). UPWARD. GitHub. Retrieved August 30, 2024, from https://github.com/NCBI-Hackathons/UPWARD
Northeastern University. (2018, April 23). Student chapter of the National Organization for Rare Disorders formed at Northeastern. College of Science at Northeastern University. https://cos.northeastern.edu/news/student-chapter-national-organization-rare-disorders-formed-northeastern/
Stanford University. (n.d.). Hackathons. Stanford Medicine. https://rttp.stanford.edu/hackathons
University of Colorado Anschutz Medical Campus. (n.d.). Charcot-Marie-Tooth disease: Foot deformities. https://medschool.cuanschutz.edu/docs/librariesprovider65/courtney-grimsrud/patient-handouts/charcot-marie-tooth-disease-foot-deformities.pdf?sfvrsn=768f92ba_2