The next orphan disease we want to focus on is the Marfan syndrome (MFS). Check out Part 1 before diving deeper with this Part 2 of MFS.
Disclaimer: Since we just touch on some facts in this article, more in-depth information and contacts for affected patients can be found here: https://marfan.org/
How is MFS inherited?
The inheritance pattern is autosomal dominant, but there have also been sporadic cases reported, with about 75% of cases having an affected parent, while the remaining cases result from a new FBN1 mutation (de novo). Even though there is significant clinical variation within families, pathogenic FBN1 mutations always lead to Marfan syndrome with full clinical penetrance.
How is MFS diagnosed?
Diagnosing Marfan syndrome can be challenging due to the considerable variation in symptoms among individuals. Since the symptoms may not manifest in childhood, the condition might not be recognized until adolescence. Accurate diagnosis is challenging and requires meeting specific genetic, phenotypic, and inheritance criteria to distinguish MFS from similar disorders. The diagnosis of MFS involves a physical exam, family history assessment, and evaluation based on diagnostic criteria like the Ghent criteria.
The Ghent criteria, which consist of major and minor clinical signs, have been internationally established as diagnostic criteria to assist in the diagnosis of Marfan syndrome. To identify mutations in the FBN1 gene or other relevant genes genetic testing is performed, although not all cases will have identifiable mutations. Additional tests such as echocardiography, ophthalmic exams, and cardiovascular imaging assess organ involvement, especially cardiovascular system and the aorta.
Treatments and Outlook
There is no treatment for MFS, the treatment is symptomatic. The main goals of the treatment management are to control aortic enlargement by using beta-blockers and reducing strenuous physical activities and regularly monitor the aorta, with annual echocardiograms, to allow for timely replacement before aortic dissection occurs. Surgery may be considered for skeletal issues like scoliosis or thoracic deformities, as well as for ocular problems such as lens replacement or laser treatment. Other treatments focus on relieving symptoms and improving the patient's quality of life. The outlook is determined by the extent of aortic involvement. With consistent monitoring and proper care, patients today can expect a life span nearly equal to that of the general population.
That is where our technology platform DESTiNED comes into place and will hopefully help those, suffering from orphan indications such as MFS.
Elastrin´s DESTiNED platform is based on nanoparticles loaded with Pentagalloylglucose (PGG) and conjugated to an antibody specifically targeting degraded elastin. PGG was shown in previous in vivo studies to restore damaged elastic fibers in vessels walls and reverse aneurysm formation. PGG has the ability to interact with monomeric Tropoelastin, a building block of elastin, facilitating the synthesis and organization of elastin. Furthermore, it enhances the stability of elastin by promoting cross-linkage. Additionally, PGG exhibits inhibitory effects on enzymes like matrix metalloproteinases, which are associated with vascular inflammation, as well as elastase, thereby reducing inflammation and elastin degradation.
By using antibody coated nanoparticles The DESTiNED platform is targeting the drug to the site of action, the damaged elastic fibers. Shown in aneurysms, PGG effectively reversed aortic dilation, mitigated inflammation, restored the integrity of the elastic lamina, and enhanced the mechanical properties of the aorta at the location of the aneurysm. In MFS, dysfunctional fibrillin-1 can result in decreased elastin content within the elastic media, elastic fiber fragmentation, and a reduced number of elastic lamellae. PGG could potentially exhibit restorative effects in individuals with Marfan syndrome (MFS) and has the potential as a treatment for MFS patients.
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