Successful Treatment with Patisiran in Amyloid Polyneuropathy Harboring His90Asn Mutation in the Gene.

Hereditary transthyretin amyloidosis (hATTR) is a multisystemic, rare, inherited, progressive and adult-onset disease, affecting the sensory-motor nerves, heart, autonomic function, and other organs. There are over 130 mutations known in the gene. The His90Asn mutation has been previously reported in several reports, but its pathogenetic role is still debated.

Effect of tauroursodeoxycholic acid on survival and safety in amyotrophic lateral sclerosis: a retrospective population-based cohort study.

Background: Oral tauroursodeoxycholic acid (TUDCA) is a commercial drug currently tested in patients with amyotrophic lateral sclerosis (ALS) both singly and combined with sodium phenylbutyrate. This retrospective study aimed to investigate, in a real-world setting, whether TUDCA had an impact on the overall survival of patients with ALS who were treated with this drug compared to those patients who received standard care only.

Methods: This propensity score-matched study was conducted in the Emilia Romagna Region (Italy), which has had an ALS regional registry since 2009.

Retrospective observational study on the use of acetyl-L-carnitine in ALS.

ALCAR (Acetyl-L-carnitine) is a donor of acetyl groups and increases the intracellular levels of carnitine, the primary transporter of fatty acids across the mitochondrial membranes. In vivo studies showed that ALCAR decrease oxidative stress markers and pro-inflammatory cytokines. In a previous double-blind placebo-controlled phase II trial showed positive effects on self-sufficiency (defined as a score of 3+ on the ALSFRS-R items for swallowing, cutting food and handling utensils, and walking) ALSFRS-R total score and FVC.

Insight into Elderly ALS Patients in the Emilia Romagna Region: Epidemiological and Clinical Features of Late-Onset ALS in a Prospective, Population-Based Study.

Few studies have focused on elderly (>80 years) amyotrophic lateral sclerosis (ALS) patients, who represent a fragile subgroup generally not included in clinical trials and often neglected because they are more difficult to diagnose and manage. We analyzed the clinical and genetic features of very late-onset ALS patients through a prospective, population-based study in the Emilia Romagna Region of Italy. From 2009 to 2019, 222 (13.

Co-Occurrence of Multiple Sclerosis and Amyotrophic Lateral Sclerosis in an FUS-Mutated Patient: A Case Report.

A concomitant presentation of relapsing remitting multiple sclerosis (RRMS) and amyotrophic lateral sclerosis (ALS) is quite rare. However, a review of the literature showed an increased co-occurrence of both diseases, including in genetically determined cases. We report the case of a 49-year-old woman with a history of RRMS who developed a progressive subacute loss of strength in her left arm.

Epidemiological, Clinical and Genetic Features of ALS in the Last Decade: A Prospective Population-Based Study in the Emilia Romagna Region of Italy.

Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype-phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS.

Broadly neutralizing antiviral responses induced by a single-molecule HPV vaccine based on thermostable thioredoxin-L2 multiepitope nanoparticles.

Vaccines targeting the human papillomavirus (HPV) minor capsid protein L2 are emerging as chemico-physically robust and broadly protective alternatives to the current HPV (L1-VLP) vaccines. We have previously developed a trivalent L2 vaccine prototype exploiting Pyrococcus furiosus thioredoxin (PfTrx) as a thermostable scaffold for the separate presentation of three distinct HPV L2(20-38) epitopes. With the aim of achieving a highly immunogenic, yet simpler and more GMP-production affordable formulation, we report here on a novel thermostable nanoparticle vaccine relying on genetic fusion of PfTrx-L2 with the heptamerizing coiled-coil polypeptide OVX313.

Thioredoxin-Displayed Multipeptide Immunogens.

Fusion to carrier proteins is an effective strategy for stabilizing and providing immunogenicity to peptide epitopes. This is commonly achieved by cross-linking of chemically synthesized peptides to carrier proteins. An alternative approach is internal grafting of selected peptide epitopes to a scaffold protein via double stranded-oligonucleotide insertion or gene synthesis, followed by recombinant expression of the resulting chimeric polypeptide.

Robust In Vitro and In Vivo Neutralization against Multiple High-Risk HPV Types Induced by a Thermostable Thioredoxin-L2 Vaccine.

Current prophylactic virus-like particle (VLP) human papillomavirus (HPV) vaccines are based on the L1 major capsid protein and provide robust but virus type-restricted protection. Moreover, VLP vaccines have a high production cost, require cold-chain storage, and are thus not readily implementable in developing countries, which endure 85% of the cervical cancer-related death burden worldwide. In contrast with L1, immunization with minor capsid protein L2 elicits broad cross-neutralization, and we previously showed that insertion of a peptide spanning amino acids 20-38 of L2 into bacterial thioredoxin (Trx) greatly enhances its immunogenicity.

New phenotype and neonatal onset of sodium channel myotonia in a child with a novel mutation of SCN4A gene.

Myotonia is rare in newborns, and not well-known. Mutations of the skeletal muscle sodium channel gene SCN4A are associated with several neuromuscular disorders including sodium channel myotonias. We reported a 4-year-old female who presented with diffuse stiffness, bilateral clubfoot, hip dislocation, facial dysmorphisms and myotonia at birth.

A high-performance thioredoxin-based scaffold for peptide immunogen construction: proof-of-concept testing with a human papillomavirus epitope.

Escherichia coli thioredoxin has been previously exploited as a scaffold for the presentation/stabilization of peptide aptamers as well as to confer immunogenicity to peptide epitopes. Here we focused on other key features of thioredoxin that are of general interest for the production of safer and more effective peptide immunogens, such as a high thermal stability, lack of cross-reactivity and a low-cost of production. We identified thioredoxin from the archaebacterium Pyrococcus furiosus (PfTrx) as a novel scaffold meeting all the above criteria.

A three component mix of thioredoxin-L2 antigens elicits broadly neutralizing responses against oncogenic human papillomaviruses.

Current human papillomavirus (HPV) vaccines based on major capsid protein L1 virus-like particles (VLP) provide potent type-specific protection against vaccine-type viruses (mainly HPV16 and 18), but cross-protect against only a small subset of the approximately 15 oncogenic HPV types. It is estimated that L1-VLP vaccines, which require a fairly complex production system and are still quite costly, fail to cover 20-30% of HPV cervical cancers worldwide, especially in low-resource countries. Alternative antigens relying on the N-terminal region of minor capsid protein L2 are intrinsically less immunogenic but capable of eliciting broadly neutralizing responses.

Concurrent chronic motor axonal polyneuropathy and synaptic impairment of neuromuscular junction.

Polyneuropathies may exhibits clinical, electrophysiologic signs of neuromuscular junction impairment. Distal motor nerve terminals and neuromuscular junction contain pre or postsynaptically specific targets for circulating autoantibodies, if present in neuropathies. Motor nerve terminal blockade either reversible or permanent is a putative factor of muscle weakness.

The N-terminal region of the human papillomavirus L2 protein contains overlapping binding sites for neutralizing, cross-neutralizing and non-neutralizing antibodies.

The N-terminal region of the human papillomavirus (HPV) L2 protein has been shown to contain immune epitopes able to induce the production of neutralizing and cross-neutralizing antibodies (Gambhira et al., 2007; Kawana et al., 1999).

Rapidly progressive amyotrophic lateral sclerosis in a young patient with hereditary neuropathy with liability to pressure palsies.

We describe the rare case of a young woman with hereditary neuropathy with liability to compression palsy (HNPP), who developed a rapidly progressive ALS. We suggest that underexpression of PMP22 protein in the nervous system might interfere with motor neuron function by impairing myelin formation and exposure of the axon to injury. Patients with ALS and evidence of demyelination should be screened for HNPP.

Potent anti-HPV immune responses induced by tandem repeats of the HPV16 L2 (20 -- 38) peptide displayed on bacterial thioredoxin.

The minor capsid protein L2 is a promising candidate for the construction of an anti-human papillomavirus (HPV) broadly protective vaccine for the prophylaxis of cervical cancer. However, L2-derived peptides are usually poorly immunogenic and extensive knowledge on the most relevant (cross)neutralizing epitope(s) is still needed. We systematically examined the immunogenicity and virus neutralization potential of six peptides encompassing the N-terminal (amino acids 1 -- 120) region of HPV16 L2 (20 -- 38; 28 -- 42; 56 -- 75; 64 -- 81; 96 -- 115; 108 -- 120) using bacterial thioredoxin (Trx) as a novel peptide scaffold.