New Grant Funds Novel Approach to Heal Bones in Rare Morquio A Syndrome

BOSTON, MA – January 16, 2026 – In a significant step toward addressing a critical unmet need in rare disease treatment, Crosswalk Therapeutics announced today it has received a research grant from the National MPS Society. The funding will fuel the early development of a next-generation therapy for Morquio A syndrome, a rare genetic disorder that progressively ravages the skeleton, leaving current treatments behind.

The grant supports a novel approach using an engineered “fusion protein” designed to deliver a therapeutic enzyme directly to bone and cartilage—tissues that have remained stubbornly beyond the reach of existing enzyme replacement therapies. This initiative represents a targeted effort to alleviate the most debilitating aspects of the disease, potentially offering new hope to patients and families.

A Devastating Toll on the Skeleton

Morquio A syndrome, or Mucopolysaccharidosis IVA (MPS IVA), is an inherited lysosomal storage disorder affecting an estimated 1 in 200,000 to 300,000 newborns. Individuals with the condition lack a functional version of the enzyme N-acetylgalactosamine-6-sulfatase (GALNS). Without this enzyme, the body cannot break down specific complex sugars called glycosaminoglycans (GAGs), particularly keratan sulfate and chondroitin-6-sulfate.

This leads to a toxic accumulation of GAGs within cells, primarily wreaking havoc on the skeletal system. While patients often appear healthy at birth, symptoms emerge in early childhood and worsen over time. The consequences are severe and systemic, including profound short stature, spinal deformities like kyphoscoliosis, a protruding chest, and joint hypermobility. One of the most life-threatening complications is the underdevelopment of a vertebra in the neck (odontoid hypoplasia), which can cause spinal cord compression.
The progressive nature of the disease often leads to significant pain, mobility challenges, and a reliance on wheelchairs. Respiratory function is also frequently compromised due to deformities of the chest wall, contributing significantly to morbidity and mortality.

The Challenge of Reaching the Target

For the past decade, the primary treatment for Morquio A has been enzyme replacement therapy (ERT). The FDA-approved drug, elosulfase alfa (Vimizim®), is a recombinant form of the missing GALNS enzyme administered through weekly intravenous infusions. Clinical trials have shown that ERT can improve endurance, as measured by the six-minute walk test, and reduce GAG levels in the urine, indicating some systemic effect.

However, the therapy’s impact on the skeleton—the root of the disease’s greatest burden—has been profoundly limited. The core challenge lies in drug delivery. Bone and, in particular, cartilage are avascular tissues, meaning they lack a direct blood supply. This biological barrier prevents the large enzyme molecules circulating in the bloodstream from effectively penetrating the very tissues where GAG accumulation causes the most damage. As a result, the skeletal deformities and joint disease that define Morquio A continue to progress in many patients, even while on treatment.

This limitation has left a significant gap in care, forcing patients to rely on extensive orthopedic surgeries and other supportive measures to manage their symptoms without a therapy that can halt or reverse the underlying skeletal pathology.

Engineering a Smarter Enzyme

Crosswalk Therapeutics aims to overcome this fundamental barrier with a fundamentally different approach. The research funded by the National MPS Society will advance a fusion protein, a sophisticated bioengineered therapeutic. This technology involves chemically linking the recombinant GALNS enzyme to a separate protein or peptide that acts as a targeting moiety—a kind of molecular GPS that guides the therapy directly to bone and cartilage.

While the company has not disclosed the exact nature of its targeting technology, similar strategies in development have involved using molecules with a natural affinity for bone mineral, such as bisphosphonates or specific acidic peptides. By creating a fusion protein, the goal is to ensure the therapeutic enzyme not only circulates in the body but actively binds to and is absorbed by skeletal tissues.

“Morquio A syndrome is a devastating condition with significant unmet need, particularly in skeletal disease,” said Madhu Natarajan, PhD, Chief Executive Officer of Crosswalk Therapeutics, in a statement. “This grant enables our team to pursue a fundamentally different approach to enzyme therapy, focused on improving enzyme design and tissue delivery, while leveraging modern computational approaches to shorten development timelines while maintaining a rigorous preclinical focus.” If successful, this strategy could allow the enzyme to break down the accumulated GAGs within skeletal cells, potentially slowing or even preventing the relentless progression of bone and joint disease.

Patient Advocacy as a Catalyst for Innovation

The grant from the National MPS Society highlights the essential role that patient advocacy organizations play in driving progress in the rare disease field. For small biotechnology companies like Crosswalk, which are often focused on high-risk, scientifically ambitious projects, non-dilutive funding from such groups is a critical lifeline. It provides the initial capital needed to generate proof-of-concept data without giving up equity, validating the scientific premise and making the program more attractive for future, larger-scale investment.

These non-profits, deeply connected to the patient communities they serve, are uniquely positioned to identify and support research that directly addresses the most urgent unmet needs. Their grant programs often serve as the seed corn for breakthroughs that might otherwise be considered too niche or too early-stage for traditional venture capital or large pharmaceutical companies.

“Through our grant programs, we aim to support promising research that addresses unmet needs within the MPS community,” stated Scott Loiler, PhD, Chief Scientific Officer of the National MPS Society. “This project reflects our commitment to advancing science that may inform future treatment strategies for individuals living with Morquio A syndrome.”

A Broader Horizon for Rare Disease Treatment

Crosswalk’s project enters a therapeutic landscape that is slowly expanding to include other advanced modalities, including gene therapy, with a clinical trial for Morquio A being organized by Nemours Children's Health. However, improving upon the established and widely used ERT platform remains a vital and parallel path forward.

The potential impact of Crosswalk's technology extends beyond a single condition. The challenge of delivering therapies to specific, hard-to-reach tissues is a common theme across many of the more than 70 identified lysosomal storage diseases. The company has noted that its underlying fusion protein platform is designed to be adaptable, meaning a successful outcome in Morquio A could pave the way for developing similarly targeted enzymes for other rare disorders where tissue access limits therapeutic effectiveness. This positions the Boston-based company not just as a developer of a single product, but as a creator of a platform aimed at solving one of the most persistent problems in modern drug delivery for genetic diseases.