The LightCure Consortium is developing a targeted photodynamic therapy, that one day could be a promising treatment for congenital hyperinsulinism (HI). HI is the most frequent cause of severe, persistent hypoglycemia in newborn babies and children, occurring in approximately 1/28,000 births. HI can be life-threatening with few treatment options; complications of the condition can include brain injuries. developmental disorders and epilepsy.
The scientific researchers who are a part of the LightCure consortium hypothesize that via a minimally invasive process, light can be used to target and eliminate improperly working pancreatic cells. This project is made possible by a grant of just over €8.2M from the European Union research arm Horizon Europe and encompasses CHI’s work to strengthen patient engagement and raise worldwide awareness of HI and its myriad challenges.
The 11-member consortium, led by Martin Gotthardt, of Stichting Radboud Universitair Medisch Centrum (Radboud) in the Netherlands hopes that by the end of this decade, physicians will have full human use of the photodynamic therapy, which would be applied shortly after birth and tailored for individual patients to best eliminate the side effects of existing treatments. Preclinical testing has produced extremely encouraging results. “We can foresee a day when, as a newborn is found to have HI, that baby’s quality of life will not be compromised,” Gotthardt says. “This development means that within little more than a handful of years, families may no longer have to choose between evils, faced with the replacement of HI with another disease characterized by severe secondary morbidity.” Currently, to treat HI, many patients undergo pancreatic surgery, which results in patients developing diabetes and pancreatic insufficiency.
To develop this cutting-edge therapy, scientists at the consortium member research centers have successfully isolated an extended amino acid chain that can be modified to bind only to the pancreatic cells responsible for the overproduction of insulin, the root of HI and its complications. The modification entails equipping the amino acid chain, a polypeptide called EX, with a photosynthesizer shown to inhibit the problematic beta cells. The photosensitizer, 700DX, can be activated by light of a specific wavelength to produce radical oxygen species leading to damage – or, if necessary, inducing total destruction – of only the cells in question; hence, the principle of targeted photodynamic therapy (tPDT).
Further, by dosing the photosynthesizer-equipped polypeptide, or EX700DX, to a particular patient and then activating it by exposure to light of a predefined wavelength, the treatment provides double specificity. This will allow physicians injecting their patients with EX700DX to normalize the patients’ blood-glucose levels, thereby avoiding the morbidity associated with current HI management.
HI requires complex management to maintain stable blood sugar. This can include multiple treatments, strict feeding schedules, or G-tubes to ensure continuous feeding. This can put a burden not only on the individual living with HI, but also on their family, especially their caregivers.