Individualized trials of Sanfilippo anti-inflammatory therapies sought

Researchers in Europe propose model to weigh risks, benefits of certain treatments

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Researchers are calling for individualized clinical trials that would test the effects of anti-inflammatory therapies for Sanfilippo syndrome and related conditions.

A team of scientists from Europe has published a paper that outlines how such trials can be conducted and offered recommendations for specific therapies to test in specific situations.

“We expect that the model will substantially facilitate the use of [individual treatment trials] with immunomodulatory drugs to improve the treatability of” Sanfilippo and similar disorders, the researchers wrote in “An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis,” which was published in Pharmaceutics.

Clinical trials are the gold standard for testing an experimental therapy, but conducting them for rare diseases like Sanfilippo isn’t easy — the rarity of these conditions makes it hard to find enough participants and trials generally are only open to patients who meet certain criteria, which can be restrictive in some cases.

Individual treatment trials (ITTs), also called n-of-one trials, are where an experimental therapy is given to a single patient. Since they are small and personalized, it’s hard to generalize their results, but these studies “are a valid and time- and cost-efficient way to close the gap between evidence and practice and facilitate personalized medicine,” the researchers wrote. They called the trials particularly valuable for “rare diseases with high unmet clinical needs and unsatisfying treatment options,” such as Sanfilippo syndrome.

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The benefit of ITTs in treating Sanfilippo syndrome

Sanfilippo is caused by mutations that lead to the toxic buildup of the sugar molecule heparan sulfate in brain cells, causing progressive damage. Sanfilippo is one of a broader category of genetic diseases called mucopolysaccharidoses (MPSs), which feature the toxic buildup of certain sugar molecules.

Theses buildups can trigger inflammation and it’s thought that the continual activation of inflammatory pathways may worsen these diseases. As such, anti-inflammatory medications might be beneficial to test in ITTs, leading the researchers to review the available scientific literature and identify four anti-inflammatory drugs — adalimumab, abatacept, anakinra, and cladribine — that could have a potential effect in MPSs.

For Sanfilippo, the researchers suggested that ITTs should prioritize patients who were diagnosed early and are early in the course of their disease. They recommended anakinra as a first-line treatment. This therapy was tested in two dozen Sanfilippo patients in a Phase 2/3 clinical trial (NCT04018755). The trial has finished, but results aren’t available yet.

Since anakinra can cause kidney damage, the researchers recommended adalimumab as a first-line treatment for those with known kidney damage. Cladribine, which is approved for multiple sclerosis, was recommended as second-line treatment.

To aid in designing ITTs, the researchers outlined some of the key risks and benefits to weigh when deciding on an experimental treatment, and developed a mathematical model to help contextualize the risks.

The tool “will allow for weighing [of risk/benefits] by the individual patients/parents that consider an ITT,” the researchers wrote, adding it considers “the importance and probability of intended and adverse effects and, thus, provides an ideal foundation for an evidence-based, personalized decision-making process with regard to ITTs.”

The researchers are making their model available to interested MPS specialty centers to spur more ITTs to investigate the effects of anti-inflammatory therapies. They said the tool can be continuously updated as more ITTs are completed and more is learned about therapies’ effects.

“The model is not intended to be fully finished yet, but rather subject to work in progress and future versions and modifications will be provided to expert centers continuously,” they wrote.