Top Rare Disease News of the Week—August 19, 2018

#5: New Diagnostic Test Accurately Differentiates Diabetes Insipidus from Polyuria Polydipsia Syndrome

Investigators from the University of Basel and University Hospital Basel, in Switzerland, have found a better way to test for diabetes insipidus than the previously-used and oft-unpleasant water deprivation test.

In diabetes insipidus, pituitary glands lack the hormone vasopressin, therefore, leading to a salt content disregulation in the body. Without the ability to concentrate their urine, patients lose a lot of fluid and have to drink water constantly to prevent dehydration.

Of course, drinking water is recommended, but drinking a lot of water is rarely a remarkable feat. Drinking by the liter—a condition known as polyuria-polydipsia syndrome—can be part of a daily habit, or even stem from mental illness, but is different from diabetes insipidus due to the vasopressin deficiency.

#4: UB25 Protein May Reduce Neurodegeneration in Huntington’s Disease

Read more about the diabetes insipidus.A mechanism capable of blocking the accumulation of toxin protein aggregates responsible for neurodegeneration in Huntington’s disease has been identified by investigators at the University of Cologne’s Cluster of Excellence for Aging Research (CECAD).

By examining the underlying mechanisms of the rare disease, investigators were able to identify a protein, referred to as UBR5, a ubiquitin ligase which serves as a protective mechanism for cells and encourages the degradation of mutant huntingtin.

For the study, published in the journal Nature Communications, the investigative team utilized induced pluripotent stem cells (iPSC) derived from patients with Huntington’s disease, which can undergo unlimited self-renewal while maintaining their ability to differentiate into any cell type, such as neurons; iPSCs exhibit a striking ability to avoid the toxic aggregation of polyQ-expanded huntingtin (HTT), the mutant protein underlying Huntington’s disease.

#3: FDA Approves Stiripentol to Treat Seizures Associated with Dravet Syndrome

Read more about the UBR5 protein.The US Food and Drug Administration (FDA) has approved stiripentol (Diacomit) for the treatment of seizures associated with Dravet syndrome, a rare form of epilepsy.

Currently, stiripentol is indicated for use in patients 2 years of age and older who are taking clobazam. To date, no clinical data supporting the use of stiripentol as a monotherapy in Dravet syndrome is available.

Indications and usage with stiripentol include a dosage of 50 mg/kg/day, to be administered orally in 2 or 3 divided doses (16.67 mg/kg three times daily or 25 mg/kg twice daily) with a gradually reduced dose or discontinued dose. Stiripentol is available as both capsules for oral use and powder for oral suspension.

#2: FDA Approves Lanadelumab for Hereditary Angioedema

Read more about stiripentol for Dravet syndrome.This afternoon, August 23, 2018, the US Food and Drug Administration (FDA) approved the first monoclonal antibody, Shire Pharmaceutical’s lanadelumab (Takhzyro, SHP643), for the treatment of types I and II hereditary angioedema (HAE) in patients aged 12 years and older.

Used to prevent swelling attacks from occurring, lanadelumab is a plasma kallikrein inhibitor.

A multicenter, randomized, double-blind, placebo-controlled, parallel-group study in 125 patients with HAE served as the basis for the approval. For a 26-week treatment period, lanadelumab was evaluated in patients with HAE type I and II aged ≥ 12 years of age, who were split into 3 dosing arms: those who would receive 150 mg or 300 mg every 4 weeks; those who would receive 300 mg every 2 weeks; and those who would receive placebo.

#1: New Subtype of Multiple Sclerosis Discovered

Read more about lanadelumab for hereditary angioedema.A new subtype of multiple sclerosis has been discovered by investigators from the Cleveland Clinic, a discovery that provides insight into the individualized nature of the rare disease.

Demyelination of cerebral white matter has long been considered to be the driver of neuronal degeneration and permanent neurological disability in those with multiple sclerosis (MS). However, now, for the first time, investigators found that the new subtype—referred to as myelocortical MS (MCMS)—features neuronal loss but no demyelination of the brain’s white matter.

For their research, the team of investigators, led by Bruce Trapp, PhD, set to find pathological evidence of cortical neuronal loss independent of cerebral white-matter demyelination by looking at post-mortem brains that belonged to patients with multiple sclerosis.

To do this, Dr. Trapp and his team removed the brain and spinal cords from 100 patients who had died with multiple sclerosis between May 1998 and November 2012. The team conducted their retrospective analysis of the autopsies between September 2011 and February 2018.

For the study, published in the journal Lancet Neurology, they examined centimeter-thick slices of cerebral hemispheres and identified 12 individuals with MCMS, as indicated by demyelinated lesions in the spinal cord and cerebral cortex, but none in the cerebral white matter.

Read more about the new multiple sclerosis subtype.