June 13, 2024
Morquio Syndrome (MPS-IV) Drug

Global Advances in Treatment for Rare Genetic Disorder Morquio Syndrome (MPS-IV) Drug

Morquio syndrome, also known as mucopolysaccharidosis type IV (MPS IV), is a life-threatening inherited metabolic disorder caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase (GALNS). Without this enzyme, glycosaminoglycans (GAGs) cannot be fully broken down and removed from the body, causing them to accumulate in cells, blood and connective tissues. This buildup can lead to a wide range of complications and potentially shorten a person’s lifespan. For decades, treatment options have been limited to symptom management. However, recent medical advancements are bringing hope for long-term management and quality of life improvements.

Pathophysiology and Symptoms

Morquio syndrome results from a defect in the GALNS gene preventing production of the required enzyme for breaking down keratan sulfate and chondroitin-6-sulfate. As GAG storage increases systemically over time, it causes damage to tissues and organs. Common signs and symptoms include skeletal dysplasia, spinal cord compression, joint deformities, pulmonary problems, cardiac issues, liver and spleen enlargement, clouding of the cornea, hearing loss and developmental delays. The severity and onset of symptoms vary between type A and type B, as well as among individual cases. If left untreated, Morquio Syndrome (MPS-IV) Drug, can severely impair mobility and organ function, potentially shortening lifespan.

Emerging Enzyme Replacement Therapy

For many years, the standard of care focused on symptom management through surgical interventions like spinal decompressions. However, scientists have worked to develop a Morquio Syndrome (MPS-IV) Drug. In 2021, the U.S. Food and Drug Administration approved the first enzyme replacement therapy (ERT) for Morquio syndrome – Vimizim (elosulfase alfa). Produced through recombinant DNA technology, elosulfase alfa aims to replace the missing or deficient GALNS enzyme. Early clinical trials showed the drug was generally well tolerated and helped reduce urine GAG levels when administered intravenously every week for life.

While ERT may slow disease progression, weekly infusions place an ongoing treatment burden. To improve compliance and access, drug developers are working on different delivery methods. In 2023, BioMarin Pharmaceutical hopes to gain regulatory approval for their monoclonal antibody therapy, BMN 307. Administered as monthly subcutaneous injections, BMN 307 aims to cross cellular membranes and deliver enzyme replacement throughout the body for prolonged periods. Ongoing late-stage trials are evaluating safety, tolerability and effectiveness at reducing urine GAG levels compared to historical controls. If approved, BMN 307 could offer an important new option for long-term management of Morquio syndrome symptoms.

Cell and Gene Therapies on the Horizon

Looking even further ahead, regenerative medicine approaches raise hope for a potential one-time curative treatment. Sangamo Therapeutics has seen promising early results through in vitro and animal studies using a gene therapy approach. They aim to safely deliver functional copies of the GALNS gene into the body using a deactivated virus as a vector. Initial data in mouse models showedediting and expression of the transgene at the cellular level, alongside reductions in urinary GAG. Sangamo is now conducting dose-escalating trials to evaluate the therapy’s safety, tolerability and enzyme expression in humans.

Meanwhile, researchers from UCL and Oxford University have demonstrated proof-of-concept for hematopoietic stem cell-based therapies. In preclinical work, they successfully isolated blood-forming stem cells from Morquio patient samples, genetically modified them using CRISPR-Cas9 genome editing to insert the missing GALNS gene, and transplanted the corrected cells back into mice. Six months post-transplant, the human cells had engrafted and repopulated the bone marrow – leading to reductions in urinary GAG levels and correction of underlying enzyme deficiencies. These encouraging cell and gene therapy approaches could potentially provide a one-time treatment to restore GALNS activity for life. However, more research is still needed to optimize methods, assess long-term safety and pave the way for clinical trials in humans.

Improving Global Access

While medical progress is occurring, ensuring broad access to emerging Morquio syndrome therapies remains challenging – particularly in developing nations. The ultra-rare nature and high costs of ERTs like Vimizim can place significant strain on healthcare budgets. However, patient advocacy organizations are working to expand treatment access through national reimbursement applications, innovative funding models and compassionate use programs.

Manufacturers are also exploring partnerships to register therapies globally and expand production capacity. For example, Ultragenyx – the maker of Mepsevii, an ERT approved for non-neurological manifestations of MPS VII – established GSS, a joint venture with WuXi Biologics, to locally manufacture the drug in China. This helped accelerate Chinese regulatory approval and makes the high-cost therapy more financially feasible for patients there. As scientists uncover new targets and technologies to manage Morquio syndrome, it will be crucial to pair medical advances with initiatives ensuring equitable worldwide availability of life-changing treatments.

Morquio Syndrome (MPS-IV) Drug remains an incurable genetic disorder, significant strides are being made in developing better long-term management options. Recent regulatory approvals of ERTs represent an important milestone after decades without targeted therapies. Furthermore, cell and gene therapy clinical trials hold promise for potentially curative one-time treatments. With continued research, funding, and efforts to expand global access – many affected individuals and their families now have cause for increased hope.

1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it