Impact of Tafamidis on [Tc]Tc-pyrophosphate Scintigraphy in Ala97Ser Hereditary Transthyretin amyloid cardiomyopathy: significant initial reduction with stable Long-Term effects.

Objective: Tafamidis has shown potential in slowing disease progression in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to evaluate serial changes on [Tc]Tc-pyrophosphate (PYP) scintigraphy during tafamidis treatment for hereditary ATTR-CM.

Methods: We retrospectively analyzed a prospectively collected cohort of Ala97Ser (A97S) hereditary ATTR-CM patients treated with tafamidis (61 mg/day) and a control group comprising A97S hereditary ATTR-CM patients who had not received disease-modifying medications.

Unique clinical and electrophysiological features in the peripheral nerve system in patients with sialidosis - a case series study.

Background: To investigate the peripheral nervous system involvement in  sialidosis with typical features of myoclonus, seizure, and giant waves in somatosensory evoked potentials suggesting hyperexcitability in the central nervous system.

Methods: The clinical presentation of patients with genetically confirmed sialidosis was recorded. Neurophysiological studies, including nerve conduction studies (NCSs), F-wave studies, and needle electromyography (EMG), were performed on these patients.

Biophysical mechanisms underlying tefluthrin-induced modulation of gating changes and resurgent current generation in the human Na1.4 channel.

Human skeletal muscle contraction is triggered by activation of Na1.4 channels. Na1.

Patisiran, an RNAi therapeutic for hereditary transthyretin-mediated amyloidosis: Sub-analysis in Taiwanese patients from the APOLLO study.

Background: To examine the efficacy and safety of patisiran, an RNA interference therapeutic, in patients from Taiwan with hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy.

Methods: The APOLLO phase 3 trial included patients from Taiwan who received patisiran 0.3 mg/kg intravenously or placebo once every 3 weeks (q3w) for 18 months (18 M), followed by patisiran 0.

Tafamidis improves myocardial longitudinal strain in A97S transthyretin cardiac amyloidosis.

Background: Transthyretin cardiomyopathy (ATTR-CM) is a debilitating disease that has received much attention since the emergence of novel treatments. The Transthyretin Cardiomyopathy Clinical Trial showed that tafamidis, a transthyretin tetramer stabilizer, effectively reduced the declines in functional capacity and quality of life. However, Ala97Ser (A97S) hereditary ATTR-CM is underrepresented in major ATTR-CM tafamidis trials.

FT895 Impairs Mitochondrial Function in Malignant Peripheral Nerve Sheath Tumor Cells.

Neurofibromatosis type 1 (NF1) stands as a prevalent neurocutaneous disorder. Approximately a quarter of NF1 patients experience the development of plexiform neurofibromas, potentially progressing into malignant peripheral nerve sheath tumors (MPNST). FT895, an HDAC11 inhibitor, exhibits potent anti-tumor effects on MPNST cells and enhances the cytotoxicity of cordycepin against MPNST.

A randomized, placebo-controlled study of givosiran in patients with acute hepatic porphyrias (ENVISION): Final (36-month) analysis of the Taiwan Cohort.

Background/purpose: Acute hepatic porphyrias (AHP) are rare genetic disorders associated with acute neurovisceral attacks and chronic symptoms. This analysis was conducted to examine the long-term efficacy and safety of givosiran in Taiwanese participants in the ENVISION study (NCT03338816).

Methods: Patients (age ≥12 years) with AHP and recurrent attacks were randomized to receive givosiran 2.

Growth of B16F10 cells is enhanced in DJ-1-deficiency pancreas.

Association between cancer risk and Parkinson's disease is still debated. DJ-1, a Parkinson's disease (PD)-related gene, is encoded by PARK-7 gene and its deficiency causes early-onset PD. In our last studies, it was found that the immunosuppressive microenvironment established in DJ-1 knockout (KO) mice can enhance metastasis of melanoma cells to lungs.

Tafamidis decreased cardiac amyloidosis deposition in patients with Ala97Ser hereditary transthyretin cardiomyopathy: a 12-month follow-up cohort study.

Background: Transthyretin cardiac cardiomyopathy (ATTR-CM) is a rare but life-threatening disease. Tafamidis is an effective treatment for patients with ATTR-CM, however its long-term effects on cardiac remodeling and cardiac amyloid deposition are unknown. This study aimed to used cardiac magnetic resonance (CMR) to investigate the effects of tafamidis on patients with hereditary A97S ATTR-CM.

EXPLORE B: A prospective, long-term natural history study of patients with acute hepatic porphyria with chronic symptoms.

One-year data from EXPLORE Part A showed high disease burden and impaired quality of life (QOL) in patients with acute hepatic porphyria (AHP) with recurrent attacks. We report baseline data of patients who enrolled in EXPLORE Part B for up to an additional 3 years of follow-up. EXPLORE B is a long-term, prospective study evaluating disease activity, pain intensity, and QOL in patients with AHP with ≥1 attack in the 12 months before enrollment or receiving hemin or gonadotropin-releasing hormone prophylaxis.

Comparison of clinical and neuroimaging features between NOTCH3 mutations and nongenetic spontaneous intracerebral haemorrhage.

Background And Purpose: The NOTCH3 mutation is a common cause of hereditary cerebral small vessel disease (CSVD) and may be a cause of spontaneous intracerebral haemorrhage (ICH). The aim was to investigate the clinical/imaging features for identifying the NOTCH3-mutation-related ICH.

Methods: The study was based on a cohort of 749 CSVD patients in Taiwan who received next-generation sequencing of CSVD genes including NOTCH3.

Kinetic Alterations in Resurgent Sodium Currents of Mutant Na1.4 Channel in Two Patients Affected by Paramyotonia Congenita.

Paramyotonia congenita (PMC) is a rare skeletal muscle disorder characterized by muscle stiffness upon repetitive exercise and cold exposure. PMC was reported to be caused by dominant mutations in the SCN4A gene encoding the α subunit of the Na1.4 channel.

A novel HDAC11 inhibitor potentiates the tumoricidal effects of cordycepin against malignant peripheral nerve sheath tumor through the Hippo signaling pathway.

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder. Clinically, the hallmarks of NF1 include skin pigmentation and cutaneous neurofibroma. Some NF1 patients develop plexiform neurofibroma (PN) since early childhood.

Recent Advances in RNA Therapy and Its Carriers to Treat the Single-Gene Neurological Disorders.

The development of new sequencing technologies in the post-genomic era has accelerated the identification of causative mutations of several single gene disorders. Advances in cell and animal models provide insights into the underlining pathogenesis, which facilitates the development and maturation of new treatment strategies. The progress in biochemistry and molecular biology has established a new class of therapeutics-the short RNAs and expressible long RNAs.

Cannabidiol Selectively Binds to the Voltage-Gated Sodium Channel Na1.4 in Its Slow-Inactivated State and Inhibits Sodium Current.

Cannabidiol (CBD), one of the cannabinoids from the cannabis plant, can relieve the myotonia resulting from sodium channelopathy, which manifests as repetitive discharges of muscle membrane. We investigated the binding kinetics of CBD to Na1.4 channels on the muscle membrane.

DNA Hypermethylation Involves in the Down-Regulation of Chloride Intracellular Channel 4 (CLIC4) Induced by Photodynamic Therapy.

The altered expression of chloride intracellular channel 4 (CLIC4) was reported to correlate with tumor progression. Previously, we have shown that the reduced cellular invasion induced by photodynamic therapy (PDT) is associated with suppression of CLIC4 expression in PDT-treated cells. Herein, we attempted to decipher the regulatory mechanisms involved in PDT-mediated CLIC4 suppression in A375 and MDA-MB-231 cells in vitro.

Cordycepin inhibits the proliferation of malignant peripheral nerve sheath tumor cells through the p53/Sp1/tubulin pathway.

Neurofibromatosis type 1 (NF1) is one of the most common hereditary neurocutaneous disorders. In addition to skin pigmentation and cutaneous neurofibroma, some patients developed the plexiform neurofibroma since birth. Plexiform neurofibroma has abundant Schwann cells, fibroblasts, mast cells, blood vessels, and connective tissues, which increases the risk of developing a malignant peripheral nerve sheath tumor (MPNST).

Changes in Resurgent Sodium Current Contribute to the Hyperexcitability of Muscles in Patients with Paramyotonia Congenita.

Paramyotonia congenita (PMC) is a rare hereditary skeletal muscle disorder. The major symptom, muscle stiffness, is frequently induced by cold exposure and repetitive exercise. Mutations in human gene, which encodes the α-subunit of Na1.

Changes of Resurgent Na Currents in the Na1.4 Channel Resulting from an Mutation Contributing to Sodium Channel Myotonia.

Myotonia congenita (MC) is a rare disorder characterized by stiffness and weakness of the limb and trunk muscles. Mutations in the gene encoding the alpha-subunit of the voltage-gated sodium channel Na1.4 have been reported to be responsible for sodium channel myotonia (SCM).

A Novel Treatment Modality for Malignant Peripheral Nerve Sheath Tumor Using a Dual-Effect Liposome to Combine Photodynamic Therapy and Chemotherapy.

Neurofibromatosis type 1 (NF1) is an inherited neurological disorder. Approximately 5-13% of NF1 patients may develop a malignant peripheral nerve sheath tumor (MPNST), which is a neurofibrosarcoma transformed from the plexiform neurofibroma or schwannoma. Given the large size and easy metastasis of MPNST, it remains difficult to be cured by either surgical or conventional chemotherapy.